Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Faricimab (RO6867461) in Participants With Center-Involving Diabetic Macular Edema (BOULEVARD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02699450
Recruitment Status : Completed
First Posted : March 4, 2016
Results First Posted : September 25, 2020
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetic Macular Edema
Interventions Drug: Faricimab
Drug: Ranibizumab
Enrollment 229
Recruitment Details  
Pre-assignment Details A total of 229 patients were randomized, but two participants randomized to Arm C: 6 mg Faricimab were excluded from the analysis populations due to Good Clinical Practice (GCP) non-compliance at a single site.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Period Title: Overall Study
Started [1] 90 55 82
Received at Least One Dose of Study Drug [2] 89 55 80
Completed up to Week 24 81 53 73
Completed [3] 75 50 67
Not Completed 15 5 15
Reason Not Completed
Death             2             1             2
Met Criteria for Study Exit             0             0             1
Protocol Violation             4             3             5
Lost to Follow-up             3             0             5
Physician Decision             2             0             0
Withdrawal by Subject             3             1             2
Adverse Event             1             0             0
[1]
Intent-to-Treat (ITT) Population
[2]
Safety Population
[3]
Completed Study (per pre-specified criteria)
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab Total
Hide Arm/Group Description Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study. Total of all reporting groups
Overall Number of Baseline Participants 90 55 82 227
Hide Baseline Analysis Population Description
Two participants randomized to Arm C: 6 mg Faricimab were excluded from the analysis populations due to Good Clinical Practice (GCP) non-compliance at a single site.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
All Participants Number Analyzed 90 participants 55 participants 82 participants 227 participants
62.3  (9.2) 61.5  (7.7) 60.8  (9.2) 61.6  (8.8)
Treatment-Naive Participants Number Analyzed 59 participants 54 participants 53 participants 166 participants
61.6  (9.5) 61.4  (7.7) 60.5  (9.1) 61.2  (8.8)
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
63.5  (8.7) 63.0 [2]   (NA) 61.5  (9.5) 62.6  (9.0)
[1]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants.
[2]
Standard deviation could not be calculated from data for a single participant.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 90 participants 55 participants 82 participants 227 participants
Female
36
  40.0%
35
  63.6%
36
  43.9%
107
  47.1%
Male
54
  60.0%
20
  36.4%
46
  56.1%
120
  52.9%
Treatment-Naive Participants Number Analyzed 59 participants 54 participants 53 participants 166 participants
Female
22
  37.3%
35
  64.8%
20
  37.7%
77
  46.4%
Male
37
  62.7%
19
  35.2%
33
  62.3%
89
  53.6%
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
Female
14
  45.2%
0
   0.0%
16
  55.2%
30
  49.2%
Male
17
  54.8%
1
 100.0%
13
  44.8%
31
  50.8%
[1]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 90 participants 55 participants 82 participants 227 participants
Hispanic or Latino
15
  16.7%
8
  14.5%
16
  19.5%
39
  17.2%
Not Hispanic or Latino
74
  82.2%
47
  85.5%
66
  80.5%
187
  82.4%
Unknown or Not Reported
1
   1.1%
0
   0.0%
0
   0.0%
1
   0.4%
Treatment-Naive Participants Number Analyzed 59 participants 54 participants 53 participants 166 participants
Hispanic or Latino
11
  18.6%
8
  14.8%
9
  17.0%
28
  16.9%
Not Hispanic or Latino
48
  81.4%
46
  85.2%
44
  83.0%
138
  83.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
Hispanic or Latino
4
  12.9%
0
   0.0%
7
  24.1%
11
  18.0%
Not Hispanic or Latino
26
  83.9%
1
 100.0%
22
  75.9%
49
  80.3%
Unknown or Not Reported
1
   3.2%
0
   0.0%
0
   0.0%
1
   1.6%
[1]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 90 participants 55 participants 82 participants 227 participants
American Indian or Alaska Native
1
   1.1%
0
   0.0%
2
   2.4%
3
   1.3%
Asian
0
   0.0%
0
   0.0%
1
   1.2%
1
   0.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
17
  18.9%
11
  20.0%
14
  17.1%
42
  18.5%
White
71
  78.9%
43
  78.2%
61
  74.4%
175
  77.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.1%
1
   1.8%
4
   4.9%
6
   2.6%
Treatment-Naive Participants Number Analyzed 59 participants 54 participants 53 participants 166 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
2
   3.8%
2
   1.2%
Asian
0
   0.0%
0
   0.0%
1
   1.9%
1
   0.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  15.3%
11
  20.4%
10
  18.9%
30
  18.1%
White
49
  83.1%
42
  77.8%
39
  73.6%
130
  78.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.7%
1
   1.9%
1
   1.9%
3
   1.8%
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
American Indian or Alaska Native
1
   3.2%
0
   0.0%
0
   0.0%
1
   1.6%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
8
  25.8%
0
   0.0%
4
  13.8%
12
  19.7%
White
22
  71.0%
1
 100.0%
22
  75.9%
45
  73.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
3
  10.3%
3
   4.9%
[1]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants.
Anti-VEGF Treatment Experience Status (Treatment-Naive or Previously Treated)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 55 participants 82 participants 227 participants
Treatment-Naive
59
  65.6%
54
  98.2%
53
  64.6%
166
  73.1%
Previously Treated
31
  34.4%
1
   1.8%
29
  35.4%
61
  26.9%
[1]
Measure Description: Approximately 210 participants were planned to be randomized to this study, including approximately 150 treatment-naive participants (1:1:1 to Arms A, B, and C) and approximately 60 participants (1:1 to Arms A and C) who had been previously treated with IVT anti-vascular endothelial growth factor (VEGF).
Best Corrected Visual Acuity (BCVA) ETDRS Letter Score in the Study Eye at Baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
All Participants Number Analyzed 89 participants 55 participants 80 participants 224 participants
61.51  (10.43) 61.16  (11.12) 59.48  (12.49) 60.70  (11.36)
Treatment-Naive Participants Number Analyzed 58 participants 54 participants 51 participants 163 participants
61.24  (9.87) 60.94  (11.11) 60.00  (10.95) 60.75  (10.58)
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
62.00  (11.56) 73.00 [2]   (NA) 58.55  (14.98) 60.54  (13.31)
[1]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants. This analysis included participants who had received at least one dose of study drug and had non-missing assessments at baseline.
[2]
Standard deviation could not be calculated from data for a single participant.
Previous Macular Laser Treatment Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 90 participants 55 participants 82 participants 227 participants
Previous Macular Laser Treatment
16
  17.8%
4
   7.3%
15
  18.3%
35
  15.4%
No Previous Macular Laser Treatment
74
  82.2%
51
  92.7%
67
  81.7%
192
  84.6%
Treatment-Naive Participants Number Analyzed 59 participants 54 participants 53 participants 166 participants
Previous Macular Laser Treatment
6
  10.2%
4
   7.4%
3
   5.7%
13
   7.8%
No Previous Macular Laser Treatment
53
  89.8%
50
  92.6%
50
  94.3%
153
  92.2%
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
Previous Macular Laser Treatment
10
  32.3%
0
   0.0%
12
  41.4%
22
  36.1%
No Previous Macular Laser Treatment
21
  67.7%
1
 100.0%
17
  58.6%
39
  63.9%
[1]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants.
Mean Foveal Center Point Thickness at Baseline   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Micrometers
All Participants Number Analyzed 89 participants 55 participants 80 participants 224 participants
459.88  (162.09) 494.64  (200.51) 440.50  (150.42) 461.49  (168.97)
Treatment-Naive Participants Number Analyzed 58 participants 54 participants 51 participants 163 participants
464.19  (166.00) 497.78  (201.02) 456.70  (156.12) 472.97  (175.37)
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
451.82  (156.87) 325.00 [3]   (NA) 412.02  (137.83) 430.82  (147.49)
[1]
Measure Description: Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).
[2]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants. This analysis included participants who had received at least one dose of study drug and had non-missing assessments at baseline.
[3]
Standard deviation could not be calculated from data for a single participant.
Mean Central Subfield Thickness at Baseline   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Micrometers
All Participants Number Analyzed 89 participants 55 participants 80 participants 224 participants
489.01  (136.74) 532.89  (162.72) 485.31  (130.10) 498.46  (142.04)
Treatment-Naive Participants Number Analyzed 58 participants 54 participants 51 participants 163 participants
490.88  (139.01) 535.44  (163.13) 496.47  (134.96) 507.39  (146.71)
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
485.52  (134.56) 395.00 [3]   (NA) 465.69  (120.86) 474.61  (126.79)
[1]
Measure Description: Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.
[2]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants. This analysis included participants who had received at least one dose of study drug and had non-missing assessments at baseline.
[3]
Standard deviation could not be calculated from data for a single participant.
Number of Participants with Absence/Presence of Subretinal Fluid in the Study Eye at Baseline   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 89 participants 55 participants 80 participants 224 participants
Subretinal Fluid Absent
49
  55.1%
30
  54.5%
44
  55.0%
123
  54.9%
Subretinal Fluid Present
40
  44.9%
25
  45.5%
36
  45.0%
101
  45.1%
Treatment-Naive Participants Number Analyzed 58 participants 54 participants 51 participants 163 participants
Subretinal Fluid Absent
34
  58.6%
30
  55.6%
25
  49.0%
89
  54.6%
Subretinal Fluid Present
24
  41.4%
24
  44.4%
26
  51.0%
74
  45.4%
Previously Treated Participants Number Analyzed 31 participants 1 participants 29 participants 61 participants
Subretinal Fluid Absent
15
  48.4%
0
   0.0%
19
  65.5%
34
  55.7%
Subretinal Fluid Present
16
  51.6%
1
 100.0%
10
  34.5%
27
  44.3%
[1]
Measure Description: Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.
[2]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants. This analysis included participants who had received at least one dose of study drug and had non-missing assessments at baseline.
Number of Participants with Absence/Presence of Intraretinal Fluid at Baseline   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 88 participants 55 participants 78 participants 221 participants
Intraretinal Fluid Absent
1
   1.1%
0
   0.0%
0
   0.0%
1
   0.5%
Intraretinal Fluid Present
87
  98.9%
55
 100.0%
78
 100.0%
220
  99.5%
Treatment-Naive Participants Number Analyzed 58 participants 54 participants 49 participants 161 participants
Intraretinal Fluid Absent
1
   1.7%
0
   0.0%
0
   0.0%
1
   0.6%
Intraretinal Fluid Present
57
  98.3%
54
 100.0%
49
 100.0%
160
  99.4%
Previously Treated Participants Number Analyzed 30 participants 1 participants 29 participants 60 participants
Intraretinal Fluid Absent
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Intraretinal Fluid Present
30
 100.0%
1
 100.0%
29
 100.0%
60
 100.0%
[1]
Measure Description: Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.
[2]
Measure Analysis Population Description: Baseline characteristics were analyzed for all participants, treatment-naive participants, and previously treated participants. This analysis included participants who had received at least one dose of study drug and had non-missing assessments at baseline.
1.Primary Outcome
Title Mean Change From Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Least Squares Mean (80% Confidence Interval)
Unit of Measure: BCVA letters
10.3
(8.8 to 11.9)
11.7
(10.1 to 13.3)
13.9
(12.2 to 15.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 1.4
Confidence Interval (2-Sided) 80%
-0.6 to 3.4
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 3.6
Confidence Interval (2-Sided) 80%
1.5 to 5.6
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
2.Secondary Outcome
Title Mean Change From Baseline in BCVA Letter Score at Week 24, in Previously Treated Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Least Squares Mean (80% Confidence Interval)
Unit of Measure: BCVA letters
8.9
(5.7 to 10.8)
9.6
(7.0 to 12.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 1.3
Confidence Interval (2-Sided) 80%
-2.3 to 5.0
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
3.Secondary Outcome
Title Mean Change From Baseline in BCVA Letter Score at Week 24, in All Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The primary analysis used a Linear Mixed Effects Model for Repeated Measurements. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 77 50 67
Least Squares Mean (80% Confidence Interval)
Unit of Measure: BCVA letters
9.4
(8.1 to 10.7)
11.7
(10.0 to 13.4)
12.3
(10.9 to 13.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 2.3
Confidence Interval (2-Sided) 80%
0.2 to 4.3
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline BCVA.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 2.9
Confidence Interval (2-Sided) 80%
1.1 to 4.7
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
4.Secondary Outcome
Title Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Treatment-Naive Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
35.3
(27.3 to 44.1)
36.0
(27.9 to 45.0)
42.5
(33.5 to 52.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 0.8
Confidence Interval (2-Sided) 80%
-11.3 to 12.8
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 7.3
Confidence Interval (2-Sided) 80%
-5.4 to 19.9
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
5.Secondary Outcome
Title Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in Previously Treated Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
16.8
(9.6 to 27.8)
23.2
(14.1 to 35.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.56
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value 6.4
Confidence Interval (2-Sided) 80%
-7.7 to 20.5
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
6.Secondary Outcome
Title Mean Percentage of Participants Who Gained ≥15 ETDRS Letters From Baseline BCVA Score at Week 24, in All Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 77 50 67
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
28.7
(22.7 to 35.5)
35.3
(27.4 to 44.2)
35.9
(28.9 to 43.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 6.6
Confidence Interval (2-Sided) 80%
-4.0 to 17.2
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.34
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 7.2
Confidence Interval (2-Sided) 80%
-2.6 to 17.0
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
7.Secondary Outcome
Title Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Treatment-Naive Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
69.0
(60.2 to 76.7)
78.5
(70.3 to 84.9)
75.8
(66.8 to 83.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 9.5
Confidence Interval (2-Sided) 80%
-1.6 to 20.6
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 6.8
Confidence Interval (2-Sided) 80%
-4.9 to 18.5
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
8.Secondary Outcome
Title Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in Previously Treated Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
69.0
(57.3 to 78.7)
68.4
(55.4 to 79.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -0.6
Confidence Interval (2-Sided) 80%
-16.8 to 15.5
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
9.Secondary Outcome
Title Mean Percentage of Participants With BCVA ≥69 Letters (20/40 or Better) at Week 24, in All Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 77 50 67
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
69.0
(62.1 to 75.2)
78.9
(70.8 to 85.2)
73.2
(65.9 to 79.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 9.9
Confidence Interval (2-Sided) 80%
0.1 to 19.7
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value 4.2
Confidence Interval (2-Sided) 80%
-5.3 to 13.6
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
10.Secondary Outcome
Title Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Treatment-Naive Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
11.5
(6.9 to 18.7)
8.7
(4.8 to 15.3)
9.8
(5.5 to 16.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -2.8
Confidence Interval (2-Sided) 80%
-10.5 to 4.9
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -1.8
Confidence Interval (2-Sided) 80%
-9.8 to 6.2
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
11.Secondary Outcome
Title Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in Previously Treated Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
10.5
(5.0 to 20.6)
8.2
(3.3 to 19.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -2.3
Confidence Interval (2-Sided) 80%
-12.7 to 8.2
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
12.Secondary Outcome
Title Mean Percentage of Participants With BCVA ≥84 Letters (20/20 or Better) at Week 24, in All Participants
Hide Description Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R) prior to dilating eyes by a trained and certified visual acuity examiner masked to study drug arm assignment. The BCVA examiner was masked to study eye and treatment assignment and only performed the refraction and BCVA assessment, but was not allowed to perform any other tasks involving direct care. The BCVA examiner was also masked to the BCVA letter scores of a participant's previous visits and could only know the participant's refraction data from previous visits. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The outcome measure was analyzed using a Generalized Estimating Equations Model. Missing values were not imputed; it was assumed that the data were missing at random.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 77 50 67
Least Squares Mean (80% Confidence Interval)
Unit of Measure: Percentage of participants
11.1
(7.3 to 16.6)
10.6
(6.2 to 17.5)
9.1
(5.6 to 14.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -0.5
Confidence Interval (2-Sided) 80%
-7.7 to 6.7
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Generalized Estimating Equations Model
Comments Categorical covariates: treatment group, visit, and visit by treatment group interaction term.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -2.0
Confidence Interval (2-Sided) 80%
-8.3 to 4.4
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
13.Secondary Outcome
Title Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Treatment-Naive Participants
Hide Description Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Least Squares Mean (80% Confidence Interval)
Unit of Measure: micrometers
-243.4
(-261.2 to -225.2)
-249.9
(-269.5 to -230.4)
-266.2
(-286.6 to -245.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -6.5
Confidence Interval (2-Sided) 80%
-27.8 to 14.7
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -22.8
Confidence Interval (2-Sided) 80%
-44.5 to -1.2
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
14.Secondary Outcome
Title Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in Previously Treated Participants
Hide Description Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Least Squares Mean (80% Confidence Interval)
Unit of Measure: micrometers
-162.1
(-186.9 to -137.3)
-211.3
(-237.1 to -185.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -49.2
Confidence Interval (2-Sided) 80%
-84.2 to -14.2
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
15.Secondary Outcome
Title Mean Change From Baseline in Foveal Center Point Thickness at Week 24, in All Participants
Hide Description Foveal center point thickness (FCPT) is defined as the thickness from the inner limiting membrane to the retinal pigment epithelial at the horizontal slice closest to the center of the fovea. Foveal center point thickness was measured using spectral domain optical coherence tomography (SD-OCT).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 77 50 67
Least Squares Mean (80% Confidence Interval)
Unit of Measure: micrometers
-210.7
(-225.0 to -196.4)
-228.0
(-246.4 to -209.7)
-239.9
(-255.2 to -224.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -17.3
Confidence Interval (2-Sided) 80%
-38.0 to 3.4
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline FCPT.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -29.2
Confidence Interval (2-Sided) 80%
-47.8 to -10.6
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
16.Secondary Outcome
Title Mean Change From Baseline in Central Subfield Thickness at Week 24, in Treatment-Naive Participants
Hide Description Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Least Squares Mean (80% Confidence Interval)
Unit of Measure: micrometers
-204.7
(-219.6 to -189.8)
-217.1
(-233.0 to -201.2)
-225.8
(-242.5 to -209.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -12.4
Confidence Interval (2-Sided) 80%
-29.7 to 5.0
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -21.1
Confidence Interval (2-Sided) 80%
-38.7 to -3.5
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
17.Secondary Outcome
Title Mean Change From Baseline in Central Subfield Thickness at Week 24, in Previously Treated Participants
Hide Description Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Least Squares Mean (80% Confidence Interval)
Unit of Measure: micrometers
-148.0
(-167.7 to -128.4)
-186.6
(-206.9 to -166.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -38.6
Confidence Interval (2-Sided) 80%
-65.9 to -11.3
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
18.Secondary Outcome
Title Mean Change From Baseline in Central Subfield Thickness at Week 24, in All Participants
Hide Description Central subfield thickness (CST) is defined as the mean thickness from the inner limiting membrane to the retinal pigment epithelial over the 1 millimetre (mm) central subfield. Central subfield thickness was measured using SD-OCT.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 77 50 67
Least Squares Mean (80% Confidence Interval)
Unit of Measure: micrometers
-180.2
(-191.6 to -168.8)
-200.3
(-214.8 to -185.8)
-206.9
(-219.0 to -194.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -20.1
Confidence Interval (2-Sided) 80%
-36.4 to -3.8
Estimation Comments The mean difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Mixed Effects Model of Repeated Measures
Comments Categorical covariates: treatment group, categorical visit, and visit by treatment group, stratification factors; continuous covariate: baseline CST.
Method of Estimation Estimation Parameter Difference in Least Squares Means
Estimated Value -26.7
Confidence Interval (2-Sided) 80%
-41.3 to -12.0
Estimation Comments The mean difference between arms was calculated as Arm C minus Arm A.
19.Secondary Outcome
Title Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants
Hide Description Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
4.08
(0.46 to 7.70)
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4948
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value -4.08
Confidence Interval (2-Sided) 80%
-7.70 to -0.46
Estimation Comments The difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4960
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value -4.08
Confidence Interval (2-Sided) 80%
-7.70 to -0.46
Estimation Comments The difference between arms was calculated as Arm C minus Arm A.
20.Secondary Outcome
Title Percentage of Participants With Presence of Subretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants
Hide Description Subretinal fluid is defined as the presence of fluid between the retina and the retinal pigment epithelium. Resolution of subretinal fluid was measured using SD-OCT.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
7.14
(0.91 to 13.38)
4.35
(0.00 to 9.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value -2.80
Confidence Interval (2-Sided) 80%
-11.08 to 5.49
Estimation Comments The difference between arms was calculated as Arm C minus Arm A.
21.Secondary Outcome
Title Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Treatment-Naive Participants
Hide Description Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 49 49 44
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
87.76
(81.75 to 93.76)
81.63
(74.54 to 88.72)
90.91
(85.35 to 96.46)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm B: 1.5 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5759
Comments There was no formal correction for multiple comparisons. Test for Arm B vs. Arm A was carried out at one-sided 10% alpha.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value -6.12
Confidence Interval (2-Sided) 80%
-15.41 to 3.17
Estimation Comments The difference between arms was calculated as Arm B minus Arm A.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arms (Arms B and C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): Either of the faricimab treatment arms (Arm B or C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7437
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value 3.15
Confidence Interval (2-Sided) 80%
-5.02 to 11.33
Estimation Comments The difference between arms was calculated as Arm C minus Arm A.
22.Secondary Outcome
Title Percentage of Participants With Presence of Intraretinal Fluid in the Study Eye at Week 24, in Previously Treated Participants
Hide Description Intraretinal fluid is described as the presence of fluid within the retina. Resolution of intraretinal fluid was measured by SD-OCT.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Baseline and Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 28 23
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
89.29
(81.79 to 96.78)
91.30
(83.77 to 98.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: 0.3 mg Ranibizumab, Arm C: 6 mg Faricimab
Comments Null hypothesis (H0): There is no difference between either of the faricimab treatment arm (Arm C) and the active comparator ranibizumab treatment arm (Arm A). The alternative hypothesis (Ha): The faricimab treatment arms (Arm C) is different from the ranibizumab treatment arm (Arm A).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments There was no formal correction for multiple comparisons. Test for Arm C vs. Arm A was carried out at one-sided 10% alpha.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value 2.02
Confidence Interval (2-Sided) 80%
-8.60 to 12.64
Estimation Comments The difference between arms was calculated as Arm C minus Arm A.
23.Secondary Outcome
Title Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Treatment-Naive Participants
Hide Description Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all treatment-naive participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 45 46 36
Measure Type: Count of Participants
Unit of Measure: Participants
Leakage Present
41
  91.1%
41
  89.1%
25
  69.4%
Leakage Absent
4
   8.9%
5
  10.9%
11
  30.6%
24.Secondary Outcome
Title Number of Participants With Presence or Absence of Leakage at the Macula at Week 24, in Previously Treated Participants
Hide Description Leakage at the macula describes the leakage of fluorescein at the macula region as measured by fundus fluorescein angiography (FFA).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population: all previously treated participants who had received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study). This analysis only included participants with non-missing assessments at Week 24.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 25 1 16
Measure Type: Count of Participants
Unit of Measure: Participants
Leakage Present
24
  96.0%
1
 100.0%
14
  87.5%
Leakage Absent
1
   4.0%
0
   0.0%
2
  12.5%
25.Secondary Outcome
Title Mean Change From Baseline in the Size of the Foveal Avascular Zone at Week 24, in All Participants
Hide Description The size of the foveal avascular zone was to be measured by fundus fluorescein angiography (FFA).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the poor image quality available, size of the foveal avascular zone could not be assessed in any of the participant populations.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
26.Secondary Outcome
Title Mean Plasma Concentrations of Ranibizumab (Arm A) or Faricimab (Arms B and C) Over Time, in All Participants
Hide Description Plasma concentrations of ranibizumab were measured by an appropriate assay only from samples of participants randomized to Arm A: 0.3 mg Ranibizumab. Plasma concentrations of faricimab were measured by a specific validated enzyme-linked immunoabsorbent assay (ELISA) only from samples of participants randomized to Arm B: 1.5 mg Faricimab and Arm C: 6 mg Faricimab. Baseline was defined as the last non-missing predose assessment. The lower limit of quantification (LLOQ) for the ranibizumab and faricimab assays were 0.015 nanograms per millilitre (ng/mL) and 0.800 ng/mL, respectively. Values below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Predose at Baseline and Weeks 1, 4, 12, 20, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 90 55 82
Mean (Standard Deviation)
Unit of Measure: nanograms per millilitre (ng/mL)
Baseline Number Analyzed 34 participants 54 participants 78 participants
2.20  (7.84) 0.40  (0.00) 0.40  (0.00)
Week 1 Number Analyzed 32 participants 52 participants 68 participants
2.52  (7.57) 48.36  (22.46) 172.24  (80.59)
Week 4 Number Analyzed 33 participants 53 participants 76 participants
0.86  (2.27) 6.97  (4.96) 20.60  (13.46)
Week 12 Number Analyzed 32 participants 51 participants 71 participants
0.26  (0.48) 9.32  (5.93) 22.38  (13.63)
Week 20 Number Analyzed 28 participants 52 participants 70 participants
0.21  (0.35) 7.11  (4.64) 22.59  (18.10)
Week 24 Number Analyzed 34 participants 49 participants 64 participants
0.20  (0.44) 8.69  (5.06) 20.18  (16.37)
Week 26 Number Analyzed 25 participants 13 participants 25 participants
0.19  (0.47) 3.80  (3.28) 8.18  (6.98)
Week 28 Number Analyzed 28 participants 13 participants 29 participants
0.10  (0.16) 1.44  (2.42) 2.94  (3.07)
Week 32 Number Analyzed 22 participants 15 participants 22 participants
0.05  (0.09) 0.46  (0.23) 0.82  (0.97)
Week 36 Number Analyzed 21 participants 37 participants 53 participants
0.03  (0.05) 0.40  (0.00) 0.40  (0.00)
27.Secondary Outcome
Title Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Treatment-Naive Participants
Hide Description The concentration of free VEGF was determined in plasma samples using an enzyme-linked immunosorbent assay (ELISA) method. The lower limit of quantification (LLOQ) of the assay was 15.6 picograms per millilitre (pg/mL). Plasma free VEGF concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 59 54 53
Mean (Standard Deviation)
Unit of Measure: picograms per millilitre (pg/mL)
Baseline (BL) - Value at Visit Number Analyzed 54 participants 51 participants 48 participants
23.93  (52.75) 14.93  (19.70) 12.45  (7.62)
Change from BL at Week 1 Number Analyzed 49 participants 49 participants 44 participants
-9.44  (49.77) -3.85  (20.99) -3.61  (6.96)
Change from BL at Week 4 Number Analyzed 51 participants 50 participants 48 participants
-1.68  (21.20) -0.37  (21.76) -0.49  (9.31)
Change from BL at Week 12 Number Analyzed 47 participants 47 participants 44 participants
-3.54  (22.50) -1.61  (20.82) 1.67  (16.69)
Change from BL at Week 16 Number Analyzed 0 participants 1 participants 0 participants
0.00 [1]   (NA)
Change from BL at Week 24 Number Analyzed 43 participants 43 participants 41 participants
-7.31  (23.97) 2.92  (18.23) 2.83  (13.74)
Change from BL at Week 26 Number Analyzed 15 participants 12 participants 15 participants
-4.37  (13.09) -2.98  (6.27) -2.43  (7.08)
Change from BL at Week 28 Number Analyzed 6 participants 7 participants 4 participants
0.30  (5.87) 0.73  (12.17) 7.15  (7.73)
Change from BL at Week 32 Number Analyzed 4 participants 4 participants 4 participants
-3.30  (8.13) -35.85  (65.08) 4.50  (5.97)
Change from BL at Week 36 Number Analyzed 30 participants 34 participants 33 participants
-1.75  (14.00) 0.69  (7.71) 2.07  (10.38)
[1]
Standard deviation could not be calculated using data from a single participant.
28.Secondary Outcome
Title Baseline and Change From Baseline in Free Vascular Endothelial Growth Factor (VEGF) Plasma Levels Over Time, in Previously Treated Participants
Hide Description The concentration of free VEGF was determined in plasma samples using an enzyme-linked immunosorbent assay (ELISA) method. The lower limit of quantification (LLOQ) of the assay was 15.6 picograms per millilitre (pg/mL). Plasma free VEGF concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 31 1 29
Mean (Standard Deviation)
Unit of Measure: picograms per millilitre (pg/mL)
Baseline (BL) - Value at Visit Number Analyzed 28 participants 1 participants 26 participants
12.94  (10.00) 7.80 [1]   (NA) 16.21  (10.22)
Change from BL at Week 1 Number Analyzed 26 participants 1 participants 22 participants
0.50  (14.24) 8.20 [1]   (NA) -7.40  (12.08)
Change from BL at Week 4 Number Analyzed 28 participants 1 participants 26 participants
0.93  (15.07) 14.50 [1]   (NA) -0.80  (11.11)
Change from BL at Week 12 Number Analyzed 28 participants 1 participants 24 participants
13.83  (51.87) 39.20 [1]   (NA) 0.78  (16.55)
Change from BL at Week 16 Number Analyzed 0 participants 0 participants 1 participants
19.10 [1]   (NA)
Change from BL at Week 24 Number Analyzed 24 participants 1 participants 21 participants
6.60  (31.50) 12.40 [1]   (NA) 4.13  (27.51)
Change from BL at Week 26 Number Analyzed 10 participants 0 participants 6 participants
-0.25  (13.97) 16.65  (42.34)
Change from BL at Week 28 Number Analyzed 6 participants 0 participants 2 participants
7.32  (20.30) 0.00  (0.00)
Change from BL at Week 32 Number Analyzed 3 participants 0 participants 1 participants
-1.13  (11.24) 57.00 [1]   (NA)
Change from BL at Week 36 Number Analyzed 18 participants 1 participants 18 participants
3.05  (11.44) 21.50 [1]   (NA) 3.53  (21.58)
[1]
Standard deviation could not be calculated using data from a single participant.
29.Secondary Outcome
Title Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants
Hide Description Total Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.09 nanograms per millilitre (ng/mL). Plasma total Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 59 54 53
Mean (Standard Deviation)
Unit of Measure: nanograms per millilitre (ng/mL)
Baseline (BL) - Value at Visit Number Analyzed 53 participants 51 participants 49 participants
2.77  (2.01) 2.07  (0.91) 2.30  (1.88)
Change from BL at Week 1 Number Analyzed 48 participants 48 participants 45 participants
0.07  (0.60) 0.04  (0.80) 0.75  (0.79)
Change from BL at Week 4 Number Analyzed 50 participants 49 participants 48 participants
0.14  (0.72) 0.05  (0.63) 0.24  (0.79)
Change from BL at Week 12 Number Analyzed 47 participants 48 participants 46 participants
0.06  (0.66) 0.14  (0.51) 0.18  (1.02)
Change from BL at Week 16 Number Analyzed 0 participants 1 participants 0 participants
-0.08 [1]   (NA)
Change from BL at Week 24 Number Analyzed 23 participants 35 participants 35 participants
0.30  (0.80) 0.40  (0.90) 0.00  (0.61)
Change from BL at Week 26 Number Analyzed 15 participants 13 participants 15 participants
0.25  (1.37) 0.21  (0.33) 0.58  (0.78)
Change from BL at Week 28 Number Analyzed 6 participants 5 participants 4 participants
0.11  (0.35) 0.34  (0.35) -0.20  (0.49)
Change from BL at Week 32 Number Analyzed 4 participants 5 participants 4 participants
-0.35  (0.50) 1.58  (1.91) 0.42  (0.21)
Change from BL at Week 36 Number Analyzed 29 participants 34 participants 34 participants
0.05  (0.83) 0.39  (1.45) -0.02  (0.83)
[1]
Standard deviation could not be calculated using data from a single participant.
30.Secondary Outcome
Title Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Treatment-Naive Participants
Hide Description Free Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.9 nanograms per millilitre (ng/mL). Plasma free Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 59 54 53
Mean (Standard Deviation)
Unit of Measure: nanograms per millilitre (ng/mL)
Baseline (BL) - Value at Visit Number Analyzed 53 participants 51 participants 49 participants
3.05  (1.72) 2.38  (1.04) 2.46  (1.37)
Change from BL at Week 1 Number Analyzed 48 participants 48 participants 45 participants
-0.49  (0.46) -0.59  (0.79) 0.06  (1.01)
Change from BL at Week 4 Number Analyzed 50 participants 49 participants 48 participants
-0.36  (0.66) -0.45  (0.72) -0.22  (0.88)
Change from BL at Week 12 Number Analyzed 47 participants 48 participants 46 participants
-0.07  (0.87) 0.10  (0.68) 0.25  (1.11)
Change from BL at Week 16 Number Analyzed 0 participants 1 participants 0 participants
-0.74 [1]   (NA)
Change from BL at Week 24 Number Analyzed 24 participants 34 participants 35 participants
-0.08  (0.95) 0.19  (1.14) -0.11  (0.86)
Change from BL at Week 26 Number Analyzed 15 participants 13 participants 15 participants
-0.23  (1.27) -0.26  (0.39) 0.08  (0.76)
Change from BL at Week 28 Number Analyzed 6 participants 5 participants 4 participants
-0.56  (0.69) -0.37  (0.44) -0.54  (0.60)
Change from BL at Week 32 Number Analyzed 4 participants 5 participants 4 participants
-0.61  (0.58) 0.92  (1.83) -0.12  (0.28)
Change from BL at Week 36 Number Analyzed 29 participants 34 participants 34 participants
-0.61  (0.87) -0.15  (1.03) -0.26  (0.89)
[1]
Standard deviation could not be calculated using data from a single participant.
31.Secondary Outcome
Title Baseline and Change From Baseline in Total Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants
Hide Description Total Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.09 nanograms per millilitre (ng/mL). Plasma total Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 31 1 29
Mean (Standard Deviation)
Unit of Measure: nanograms per millilitre (ng/mL)
Baseline (BL) - Value at Visit Number Analyzed 29 participants 1 participants 26 participants
2.40  (2.34) 1.84 [1]   (NA) 2.31  (1.78)
Change from BL at Week 1 Number Analyzed 26 participants 1 participants 21 participants
0.15  (14.24) 0.11 [1]   (NA) 0.94  (1.12)
Change from BL at Week 4 Number Analyzed 28 participants 1 participants 26 participants
0.03  (0.52) -0.27 [1]   (NA) 0.14  (0.87)
Change from BL at Week 12 Number Analyzed 28 participants 1 participants 24 participants
0.33  (1.66) -0.28 [1]   (NA) -0.09  (0.46)
Change from BL at Week 16 Number Analyzed 0 participants 0 participants 1 participants
-0.21 [1]   (NA)
Change from BL at Week 24 Number Analyzed 23 participants 1 participants 20 participants
0.19  (1.22) -0.19 [1]   (NA) -0.16  (0.46)
Change from BL at Week 26 Number Analyzed 10 participants 0 participants 6 participants
-0.07  (0.64) -0.20  (0.42)
Change from BL at Week 28 Number Analyzed 6 participants 0 participants 2 participants
0.74  (2.78) -0.91  (0.35)
Change from BL at Week 32 Number Analyzed 4 participants 0 participants 1 participants
-0.04  (0.79) 0.49 [1]   (NA)
Change from BL at Week 36 Number Analyzed 18 participants 1 participants 18 participants
0.01  (0.72) -0.47 [1]   (NA) -0.13  (0.42)
[1]
Standard deviation could not be calculated using data from a single participant.
32.Secondary Outcome
Title Baseline and Change From Baseline in Free Angiopoietin-2 (Ang-2) Plasma Levels Over Time, in Previously Treated Participants
Hide Description Free Ang-2 concentrations were determined in plasma samples using an appropriate assay method. The lower limit of quantification (LLOQ) of the assay was 0.9 nanograms per millilitre (ng/mL). Plasma free Ang-2 concentrations below the limit of quantification were imputed as LLOQ divided by 2.
Time Frame Baseline and Weeks 1, 4, 12, 16, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics Population: The analysis included participants who received at least one dose of study drug grouped by treatment assigned at randomization (did not differ from actual treatment during the study) and had plasma samples available at a given study visit timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 31 1 29
Mean (Standard Deviation)
Unit of Measure: nanograms per millilitre (ng/mL)
Baseline (BL) - Value at Visit Number Analyzed 29 participants 1 participants 27 participants
2.67  (2.60) 2.08 [1]   (NA) 2.35  (1.76)
Change from BL at Week 1 Number Analyzed 26 participants 1 participants 22 participants
-0.07  (0.88) -0.04 [1]   (NA) 0.30  (0.87)
Change from BL at Week 4 Number Analyzed 28 participants 1 participants 27 participants
-0.33  (0.58) -0.28 [1]   (NA) -0.17  (0.66)
Change from BL at Week 12 Number Analyzed 28 participants 1 participants 24 participants
-0.05  (1.12) -0.65 [1]   (NA) -0.13  (0.61)
Change from BL at Week 16 Number Analyzed 0 participants 0 participants 1 participants
-0.49 [1]   (NA)
Change from BL at Week 24 Number Analyzed 21 participants 1 participants 19 participants
-0.28  (0.58) -0.49 [1]   (NA) -0.29  (0.64)
Change from BL at Week 26 Number Analyzed 10 participants 0 participants 6 participants
-0.21  (0.79) -0.16  (0.54)
Change from BL at Week 28 Number Analyzed 6 participants 0 participants 2 participants
-0.17  (1.59) -1.36  (0.83)
Change from BL at Week 32 Number Analyzed 4 participants 0 participants 1 participants
-0.59  (0.68) 0.07 [1]   (NA)
Change from BL at Week 36 Number Analyzed 18 participants 1 participants 18 participants
-0.29  (0.72) -0.72 [1]   (NA) -0.19  (0.45)
[1]
Standard deviation could not be calculated using data from a single participant.
33.Secondary Outcome
Title Safety Summary of the Number of Participants With at Least One Adverse Event During the Treatment Period (up to Week 24), in All Participants
Hide Description This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) within 28 days of the end of the treatment period (i.e., up to Week 24). AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs leading to discontinuation of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once.
Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 89 55 80
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
61
  68.5%
38
  69.1%
54
  67.5%
Ocular AE
30
  33.7%
21
  38.2%
32
  40.0%
Ocular AE in the Study Eye
22
  24.7%
16
  29.1%
22
  27.5%
Related Ocular AE in the Study Eye
1
   1.1%
0
   0.0%
2
   2.5%
Ocular AE in Study Eye Leading to Discontinuation
1
   1.1%
0
   0.0%
0
   0.0%
Serious Ocular AE in the Study Eye
1
   1.1%
0
   0.0%
1
   1.3%
Ocular AE in the Fellow Eye
19
  21.3%
14
  25.5%
18
  22.5%
Systemic AE
51
  57.3%
30
  54.5%
46
  57.5%
Related Systemic AE
0
   0.0%
0
   0.0%
2
   2.5%
Serious Systemic AE
8
   9.0%
6
  10.9%
7
   8.8%
Systemic AE Leading to Discontinuation
0
   0.0%
1
   1.8%
0
   0.0%
Any Related AE
1
   1.1%
0
   0.0%
4
   5.0%
Any Serious AE
9
  10.1%
7
  12.7%
8
  10.0%
Any Related Serious AE
0
   0.0%
0
   0.0%
0
   0.0%
AE with Fatal Outcome
2
   2.2%
1
   1.8%
2
   2.5%
34.Secondary Outcome
Title Safety Summary of the Number of Participants With at Least One Adverse Event During the Post-Treatment Observation Period, in All Participants
Hide Description This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the post-treatment observation period (i.e., from Week 24 up to Week 36). AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs leading to discontinuation of treatment with study drug, and AEs with fatal outcome. Multiple occurrences of the same AE in one individual were counted only once.
Time Frame From Week 24 up to Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 89 55 80
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
31
  34.8%
21
  38.2%
34
  42.5%
Ocular AE
11
  12.4%
7
  12.7%
12
  15.0%
Ocular AE in the Study Eye
9
  10.1%
4
   7.3%
8
  10.0%
Related Ocular AE in the Study Eye
1
   1.1%
0
   0.0%
0
   0.0%
Ocular AE in Study Eye Leading to Discontinuation
0
   0.0%
0
   0.0%
0
   0.0%
Serious Ocular AE in the Study Eye
0
   0.0%
0
   0.0%
1
   1.3%
Ocular AE in the Fellow Eye
6
   6.7%
5
   9.1%
8
  10.0%
Systemic AE
22
  24.7%
15
  27.3%
25
  31.3%
Related Systemic AE
0
   0.0%
0
   0.0%
0
   0.0%
Serious Systemic AE
2
   2.2%
3
   5.5%
4
   5.0%
Systemic AE Leading to Discontinuation
0
   0.0%
0
   0.0%
0
   0.0%
Any Related AE
1
   1.1%
0
   0.0%
0
   0.0%
Any Serious AE
2
   2.2%
3
   5.5%
5
   6.3%
Any Related Serious AE
0
   0.0%
0
   0.0%
0
   0.0%
AE with Fatal Outcome
0
   0.0%
0
   0.0%
0
   0.0%
35.Secondary Outcome
Title Number of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye During the Treatment Period by Highest Intensity, in All Participants
Hide Description The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria.
Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 89 55 80
Measure Type: Count of Participants
Unit of Measure: Participants
Study Eye - Ocular AE of Any Intensity
22
  24.7%
16
  29.1%
22
  27.5%
Study Eye - Mild Ocluar AE
20
  22.5%
15
  27.3%
21
  26.3%
Study Eye - Moderate Ocular AE
2
   2.2%
3
   5.5%
3
   3.8%
Study Eye - Severe Ocular AE
1
   1.1%
0
   0.0%
0
   0.0%
Fellow Eye - Ocular AE of Any Intensity
19
  21.3%
14
  25.5%
18
  22.5%
Fellow Eye - Mild Ocular AE
13
  14.6%
13
  23.6%
14
  17.5%
Fellow Eye - Moderate Ocular AE
7
   7.9%
1
   1.8%
5
   6.3%
Fellow Eye - Severe Ocular AE
0
   0.0%
1
   1.8%
0
   0.0%
36.Secondary Outcome
Title Number of Participants With at Least One Systemic Adverse Event During the Treatment Period by Highest Intensity, in All Participants
Hide Description The investigator assessed adverse event severity according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. Only the most severe intensity was counted for multiple occurrences of the same adverse event per participant at the preferred term level. Severity and seriousness are not synonymous; regardless of severity, some adverse events may have also met seriousness criteria.
Time Frame From Baseline up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants who had received at least one dose of the study drug, whether prematurely withdrawn from the study or not, grouped according to the actual treatment received.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 89 55 80
Measure Type: Count of Participants
Unit of Measure: Participants
Systemic AE of Any Intensity
51
  57.3%
30
  54.5%
46
  57.5%
Mild Systemic AE
34
  38.2%
19
  34.5%
34
  42.5%
Moderate Systemic AE
26
  29.2%
18
  32.7%
22
  27.5%
Severe Systemic AE
9
  10.1%
4
   7.3%
5
   6.3%
37.Secondary Outcome
Title Number of Participants With Abnormal Systolic Blood Pressure Over Time, in All Participants
Hide Description Abnormal systolic blood pressure (supine) was defined as any value outside of the standard reference range, from <70 (low) to >180 (high) millimetres of mercury (mmHg) or a change from baseline of greater than 30 mmHg (decrease or increase). Baseline was defined as the last non-missing predose assessment. Not every abnormal vital sign qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy.
Time Frame Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 26, 28, 32, and 36
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population; the number of participants with an abnormal vital sign (numerator) is reported among the number analyzed (denominator), which represents the number of participants without the abnormal vital sign at baseline and who were evaluable at a given assessment timepoint.
Arm/Group Title Arm A: 0.3 mg Ranibizumab Arm B: 1.5 mg Faricimab Arm C: 6 mg Faricimab
Hide Arm/Group Description:
Participants received 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Participants received 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant met pre-specified criteria they received a single dose of 0.3 mg ranibizumab and exited the study.
Overall Number of Participants Analyzed 89 55 80
Measure Type: Count of Participants
Unit of Measure: Participants
Week 1 - Low Number Analyzed 82 participants 53 participants 71 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 1 - High Number Analyzed 82 participants 53 participants 70 participants
1
   1.2%
3
   5.7%
0
   0.0%
Week 4 - Low Number Analyzed 87 participants 55 participants 80 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 4 - High Number Analyzed 87 participants 55 participants 78 participants
0
   0.0%
0
   0.0%
1
   1.3%
Week 8 - Low Number Analyzed 86 participants 55 participants 76 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 8 - High Number Analyzed 86 participants 55 participants 75 participants
1
   1.2%
0
   0.0%
2
   2.7%
Week 12 - Low Number Analyzed 84 participants 53 participants 75 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 12 - High Number Analyzed 84 participants 53 participants 74 participants
1
   1.2%
0
   0.0%
2
   2.7%
Week 16 - Low Number Analyzed 83 participants 53 participants 75 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 16 - High Number Analyzed 83 participants 53 participants 74 participants
0
   0.0%
1
   1.9%
1
   1.4%
Week 20 - Low Number Analyzed 80 participants 53 participants 73 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 20 - High Number Analyzed 80 participants 53 participants 72 participants
3
   3.8%
2
   3.8%
3
   4.2%
Week 24 - Low Number Analyzed 77 participants 50 participants 67 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 24 - High Number Analyzed 77 participants 50 participants 66 participants
2
   2.6%
2
   4.0%
2
   3.0%
Week 26 - Low Number Analyzed 30 participants 14 participants 28 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 26 - High Number Analyzed 30 participants 14 participants 27 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 28 - Low Number Analyzed 76 participants 49 participants 67 participants
0
   0.0%
0
   0.0%
0
   0.0%
Week 28 - High Number Analyzed 76 participants 49 participants 66 participants