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A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration (Archway)

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: NCT03677934
Recruitment Status : Completed
First Posted : September 19, 2018
Results First Posted : March 25, 2022
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Neovascular Age-Related Macular Degeneration
Interventions Drug: PDS Implant filled with 100 mg/mL Ranibizumab
Drug: Intravitreal Injections of 10 mg/mL Ranibizumab
Enrollment 415
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Period Title: Overall Study
Started 248 167
Completed 234 154
Not Completed 14 13
Reason Not Completed
Adverse Event             1             1
Death             8             4
Lost to Follow-up             3             0
Non-Compliance With Study Drug             1             0
Physician Decision             0             1
Withdrawal by Subject             1             7
Arm/Group Title PDS Implant Arm Intravitreal Arm Total
Hide Arm/Group Description Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter. Total of all reporting groups
Overall Number of Baseline Participants 248 167 415
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 248 participants 167 participants 415 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
26
  10.5%
17
  10.2%
43
  10.4%
>=65 years
222
  89.5%
150
  89.8%
372
  89.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 248 participants 167 participants 415 participants
75.2  (8.11) 74.8  (7.63) 75.0  (7.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 248 participants 167 participants 415 participants
Female
145
  58.5%
100
  59.9%
245
  59.0%
Male
103
  41.5%
67
  40.1%
170
  41.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 248 participants 167 participants 415 participants
Hispanic or Latino
7
   2.8%
8
   4.8%
15
   3.6%
Not Hispanic or Latino
240
  96.8%
159
  95.2%
399
  96.1%
Unknown or Not Reported
1
   0.4%
0
   0.0%
1
   0.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 248 participants 167 participants 415 participants
American Indian or Alaska Native
1
   0.4%
2
   1.2%
3
   0.7%
Asian
1
   0.4%
0
   0.0%
1
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   1.2%
1
   0.6%
4
   1.0%
White
240
  96.8%
161
  96.4%
401
  96.6%
More than one race
1
   0.4%
0
   0.0%
1
   0.2%
Unknown or Not Reported
2
   0.8%
3
   1.8%
5
   1.2%
1.Primary Outcome
Title Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters
Hide Description

The primary efficacy endpoint is the change in BCVA score from baseline averaged over Weeks 36 and 40 with BCVA assessed using the ETDRS chart at a starting distance of 4 meters. ETDRS = Early Treatment Diabetic Retinopathy Study.

The primary objective is to determine the NI and equivalence between the two treatment groups, as measured by the primary efficacy endpoint with a NI margin of 4.5 letters and equivalence margins of ± 4.5 letters.

A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

Time Frame Baseline, and the average of Week 36 and Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Mean (95.03% Confidence Interval)
Unit of Measure: letters
0.2
(-0.7 to 1.1)
0.5
(-0.6 to 1.6)
2.Secondary Outcome
Title Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64
Hide Description [Not Specified]
Time Frame Baseline, Week60, Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Mean (95.03% Confidence Interval)
Unit of Measure: letters
-0.4
(-1.5 to 0.7)
-0.8
(-2.2 to 0.6)
3.Secondary Outcome
Title Change From Baseline in BCVA Score Over Time
Hide Description [Not Specified]
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Mean (Standard Deviation)
Unit of Measure: letters
Week 4 Number Analyzed 246 participants 165 participants
-4.3  (0.47) -0.4  (0.58)
Week 8 Number Analyzed 247 participants 163 participants
-1.7  (0.41) 0.1  (0.51)
Week 12 Number Analyzed 244 participants 161 participants
-0.4  (0.39) 0.6  (0.48)
Week 16 Number Analyzed 244 participants 163 participants
-0.6  (0.41) 0.2  (0.5)
Week 20 Number Analyzed 242 participants 163 participants
-0.3  (0.42) 0.1  (0.52)
Week 24 Number Analyzed 245 participants 163 participants
-0.6  (0.47) 0.8  (0.57)
Week 28 Number Analyzed 243 participants 162 participants
-0.1  (0.47) 0.5  (0.57)
Week 32 Number Analyzed 241 participants 161 participants
0.2  (0.49) 0.9  (0.60)
Week 36 Number Analyzed 242 participants 160 participants
0.2  (0.47) 0.3  (0.58)
Week 40 Number Analyzed 240 participants 161 participants
0.2  (0.51) 0.7  (0.63)
Week 44 Number Analyzed 234 participants 157 participants
-0.1  (0.53) 0.6  (0.65)
Week 48 Number Analyzed 237 participants 154 participants
0.0  (0.53) -0.2  (0.65)
Week 52 Number Analyzed 209 participants 144 participants
0.1  (0.54) -0.8  (0.67)
Week 56 Number Analyzed 203 participants 150 participants
0.1  (0.56) -0.5  (0.67)
Week 60 Number Analyzed 209 participants 154 participants
-0.5  (0.58) -0.8  (0.71)
Week 64 Number Analyzed 224 participants 152 participants
-0.3  (0.59) -0.7  (0.72)
Week 68 Number Analyzed 230 participants 153 participants
-0.5  (0.64) -0.3  (0.79)
Week 72 Number Analyzed 242 participants 153 participants
-0.3  (0.64) 0.1  (0.79)
Week 76 Number Analyzed 224 participants 149 participants
-1.0  (0.68) 0.2  (0.83)
Week 80 Number Analyzed 232 participants 154 participants
-0.7  (0.64) -0.2  (0.79)
Week 84 Number Analyzed 225 participants 153 participants
-0.8  (0.62) 0.3  (0.77)
Week 88 Number Analyzed 227 participants 152 participants
-1.3  (0.62) 0.0  (0.76)
Week 92 Number Analyzed 218 participants 148 participants
-0.9  (0.63) -1.0  (0.78)
Week 96 Number Analyzed 225 participants 151 participants
-1.1  (0.68) -1.3  (0.84)
4.Secondary Outcome
Title Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse at the Average Over Week 36 and Week 40
Hide Description [Not Specified]
Time Frame Baseline, and the average of Week 36 and Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Number (95.03% Confidence Interval)
Unit of Measure: Percentage of participants
1.2
(0.0 to 2.6)
1.8
(0.0 to 3.9)
5.Secondary Outcome
Title Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time
Hide Description [Not Specified]
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Unit of Measure: Percentage of Participants
2.7 5.3
6.Secondary Outcome
Title Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better at the Average Over Week 36 and Week 40
Hide Description [Not Specified]
Time Frame Baseline, and the average of Week 36 and Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Number (95.03% Confidence Interval)
Unit of Measure: Percentage of participants
80.7
(76.9 to 84.5)
82.1
(77.5 to 86.7)
7.Secondary Outcome
Title Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time
Hide Description [Not Specified]
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Unit of Measure: Percentage of participants
75.6 78.1
8.Secondary Outcome
Title Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
Hide Description [Not Specified]
Time Frame Baseline, and the average of Week 36 and Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Number (95.03% Confidence Interval)
Unit of Measure: Percentage of participants
Loss of Visual Function <10 letters
95.1
(92.4 to 97.8)
95.1
(91.8 to 98.4)
Loss of Visual Function <5 letters
85.0
(80.5 to 89.4)
88.3
(83.4 to 93.3)
9.Secondary Outcome
Title Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time
Hide Description [Not Specified]
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Unit of Measure: Percentage of participants
<10 letters 88.9 84.1
< 5 letters 75.1 73.5
10.Secondary Outcome
Title Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40
Hide Description [Not Specified]
Time Frame Baseline up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Number (95.03% Confidence Interval)
Unit of Measure: Percentage of participants
57.8
(51.8 to 63.7)
58.9
(51.4 to 66.4)
11.Secondary Outcome
Title Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time
Hide Description [Not Specified]
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Unit of Measure: Percentage of Participants
52.4 55.6
12.Secondary Outcome
Title Change From Baseline in Center Point Thickness (CPT) at Week 36
Hide Description [Not Specified]
Time Frame Baseline to Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
Adult patients with nAMD diagnosed within 9 months and receiving at least 4 anti-VEGF intravitreal injections (with the last injection being ranibizumab), responsive to prior anti-VEGF treatment. 14 participants (7 participants in each arm) discontinued before Week 36 or the CPT value was missing (or not able to be measured on image) for the week 36 visit.
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Mean (Standard Deviation)
Unit of Measure: microns
Baseline Value Number Analyzed 248 participants 167 participants
176.9  (3.48) 177.4  (3.84)
Week 36 Number Analyzed 241 participants 160 participants
5.4  (2.91) 2.6  (3.56)
13.Secondary Outcome
Title Change From Baseline in CPT Over Time
Hide Description [Not Specified]
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Mean (Standard Deviation)
Unit of Measure: microns
Baseline Value Number Analyzed 248 participants 165 participants
176.9  (3.48) 177.4  (3.84)
Week 4 Number Analyzed 245 participants 164 participants
0.2  (2.05) 2.1  (2.51)
Week 8 Number Analyzed 247 participants 162 participants
0.3  (2.17) 3.0  (2.66)
Week 12 Number Analyzed 244 participants 161 participants
5.3  (2.87) 0.3  (3.52)
Week 16 Number Analyzed 244 participants 163 participants
6.0  (3.45) 7.3  (4.23)
Week 20 Number Analyzed 243 participants 162 participants
6.5  (2.7) 1.3  (3.31)
Week 24 Number Analyzed 243 participants 163 participants
6.7  (2.5) -0.8  (3.06)
Week 28 Number Analyzed 241 participants 162 participants
-0.4  (2.5) 1.6  (3.07)
Week 32 Number Analyzed 239 participants 162 participants
4.5  (2.69) 2.3  (3.29)
Week 36 Number Analyzed 241 participants 160 participants
5.4  (2.91) 2.7  (3.56)
Week 40 Number Analyzed 238 participants 161 participants
9.0  (3.37) 5.1  (4.13)
Week 44 Number Analyzed 232 participants 158 participants
7.3  (3.13) 3.4  (3.84)
Week 48 Number Analyzed 237 participants 153 participants
8.9  (3.55) 6.4  (4.36)
Week 52 Number Analyzed 209 participants 142 participants
3.2  (3.43) 6.6  (4.2)
Week 56 Number Analyzed 201 participants 151 participants
2.7  (3.36) 3.3  (4.10)
Week 60 Number Analyzed 209 participants 153 participants
3.9  (3.39) 2.5  (4.12)
Week 64 Number Analyzed 224 participants 152 participants
5.5  (3.54) 3.6  (4.34)
Week 68 Number Analyzed 228 participants 153 participants
8.4  (3.48) 2.1  (4.27)
Week 72 Number Analyzed 238 participants 152 participants
8.1  (3.35) 0.9  (4.14)
Week 76 Number Analyzed 221 participants 150 participants
3.4  (3.61) 0.1  (4.44)
Week 80 Number Analyzed 230 participants 153 participants
6.1  (3.56) -2.7  (4.38)
Week 84 Number Analyzed 224 participants 154 participants
8.4  (3.87) -2.0  (4.76)
Week 88 Number Analyzed 225 participants 151 participants
9.8  (3.88) -0.6  (4.77)
Week 92 Number Analyzed 217 participants 147 participants
10.3  (3.57) -1.3  (4.39)
Week 96 Number Analyzed 222 participants 151 participants
9.9  (3.64) -1.3  (4.48)
14.Secondary Outcome
Title Percentage of Participants in the PDS Implant Arm Who Undergo Supplemental Treatment With Intravitreal Ranibizumab 0.5 mg Before the First, Second, Third, and Fourth Fixed Refill-Exchange Intervals
Hide Description [Not Specified]
Time Frame Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Overall Number of Participants Analyzed 246
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1 to Week 24 Number Analyzed 246 participants
Need for supplemental treatment
4
   1.6%
No need for supplemental treatment
242
  98.4%
Week 25 to Week 48 Number Analyzed 241 participants
Need for supplemental treatment
13
   5.4%
No need for supplemental treatment
228
  94.6%
Week 49 to Week 72 Number Analyzed 231 participants
Need for supplemental treatment
12
   5.2%
No need for supplemental treatment
219
  94.8%
Week 73 to Week 96 Number Analyzed 225 participants
Need for supplemental treatment
12
   5.3%
No need for supplemental treatment
213
  94.7%
15.Secondary Outcome
Title Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study
Hide Description [Not Specified]
Time Frame Week 16 to Week 92
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population comprising all patients who are randomized and receive the study treatment, with patients grouped according to treatment actually received
Arm/Group Title PDS Implant Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Overall Number of Participants Analyzed 246
Measure Type: Number
Unit of Measure: Percentage of Participants
2 supplemental treatments 4.1
3 supplemental treatments 0.8
5 supplemental treatments 0.4
16.Secondary Outcome
Title Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs
Hide Description [Not Specified]
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Count of Participants
Unit of Measure: Participants
Ocular Events: Study Eye
242
  97.6%
87
  52.1%
Ocular Events: Fellow Eye
124
  50.0%
65
  38.9%
Non-Ocular Events
213
  85.9%
121
  72.5%
17.Secondary Outcome
Title Percentage of Participants With Adverse Events of Special Interest
Hide Description Percentage of Participants with Adverse Events of Special Interest
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprising all patients who receive the study treatment, with patients grouped according to treatment actually received.
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 248 167
Measure Type: Count of Participants
Unit of Measure: Participants
Adverse Events of Special Interest in Study Eye
64
  25.8%
18
  10.8%
Adverse Events of Special Interest in Fellow Eye
21
   8.5%
6
   3.6%
Non-Ocular Adverse Events of Special Interest
0
   0.0%
0
   0.0%
18.Secondary Outcome
Title Observed Serum Ranibizumab Concentrations at Specified Timepoints
Hide Description [Not Specified]
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Overall Number of Participants Analyzed 39 46
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Randomization Number Analyzed 39 participants 45 participants
0.125
(115%)
0.117
(78.5%)
Week 24 prerefill-exchange Number Analyzed 36 participants 44 participants
0.397
(71.1%)
0.0592
(180%)
Week 28 Number Analyzed 28 participants 35 participants
0.564
(40.7%)
0.0581
(178%)
Week 48 prerefill-exchange Number Analyzed 28 participants 39 participants
0.289
(90.6%)
0.0594
(146%)
Week 52 Number Analyzed 19 participants 35 participants
0.499
(41.7%)
0.0531
(123%)
Week 72 prerefill-exchange Number Analyzed 29 participants 30 participants
0.257
(73.7%)
0.0376
(152%)
Week 76 Number Analyzed 19 participants 32 participants
0.291
(247%)
0.0500
(127%)
Week 96 Number Analyzed 33 participants 41 participants
0.191
(154%)
0.0680
(157%)
19.Secondary Outcome
Title Estimated PK Parameter Values AUC0-6M
Hide Description AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
Arm/Group Title PDS Implant Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: day.ng/mL
59.42  (21.11)
20.Secondary Outcome
Title Estimated PK Parameter Value t1/2 After PDS Implant Insertion
Hide Description Apparent terminal half-life
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
Arm/Group Title PDS Implant Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: day
442.29  (276.92)
21.Secondary Outcome
Title Estimated PK Parameter Value Cmin
Hide Description Cmin = Minimum Serum Concentration
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
Arm/Group Title PDS Implant Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.31  (0.08)
22.Secondary Outcome
Title Estimated PK Parameter Value Cmax
Hide Description Cmax = Maximum Serum Concentration
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population excluding patients receiving intravitreal injections of ranibizumab in the study eye post PDS implant (including supplemental treatment), patients with fellow eye ranibizumab or bevacizumab treatment, or prior bevacizumab treatment in either eye.
Arm/Group Title PDS Implant Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.47  (0.16)
23.Secondary Outcome
Title Baseline Prevalence and Incidence of Treatment-Emergent ADA
Hide Description [Not Specified]
Time Frame Randomization to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The Biomarker Analysis Population consists of patients who are in the Safety Population and have sufficient data to enable assessment of potential changes in biomarkers in response to treatment during the conduct of this study. The analysis will group patients according to treatment actually received
Arm/Group Title PDS Implant Arm Intravitreal Arm
Hide Arm/Group Description:
Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter
Overall Number of Participants Analyzed 248 167
Measure Type: Number
Unit of Measure: Participants
Patients with a positive sample at time of entry into the study Number Analyzed 243 participants 162 participants
5 8
Patients with no positive samples at time of entry into the study Number Analyzed 243 participants 162 participants
238 154
Post-baseline Patients Positive for ADA Number Analyzed 247 participants 165 participants
38 21
Treatment-induced ADA Number Analyzed 247 participants 165 participants
33 15
Treatment-enhanced ADA Number Analyzed 247 participants 165 participants
0 2
Treatment unaffected or reduced Number Analyzed 247 participants 165 participants
5 6
Patients negative for ADA at all times in the study Number Analyzed 247 participants 165 participants
209 144
Time Frame Baseline up to 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intravitreal Arm PDS Implant Arm
Hide Arm/Group Description Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter. Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
All-Cause Mortality
Intravitreal Arm PDS Implant Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   5/167 (2.99%)      8/248 (3.23%)    
Hide Serious Adverse Events
Intravitreal Arm PDS Implant Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/167 (23.35%)      78/248 (31.45%)    
Blood and lymphatic system disorders     
Anaemia  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Cardiac disorders     
Coronary artery disease  1  1/167 (0.60%)  1 3/248 (1.21%)  3
Atrial fibrillation  1  2/167 (1.20%)  2 1/248 (0.40%)  1
Acute myocardial infarction  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Angina unstable  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Aortic valve incompetence  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Arteriosclerosis coronary artery  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Bradycardia  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Cardiac arrest  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Cardiac failure  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Cardiac failure acute  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Cardiac failure congestive  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Myocardial infarction  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Ear and labyrinth disorders     
Vertigo positional  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Eye disorders     
Vitreous haemorrhage  1  1/167 (0.60%)  1 2/248 (0.81%)  2
Conjunctival erosion  1  0/167 (0.00%)  0 3/248 (1.21%)  4
Retinal tear  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Visual acuity reduced  1  0/167 (0.00%)  0 1/248 (0.40%)  4
Cataract cortical  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Conjunctival bleb  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Corneal disorder  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Retinal pigment epithelial tear  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Rhegmatogenous retinal detachment  1  0/167 (0.00%)  0 2/248 (0.81%)  3
Choroidal detachment  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Necrotising retinitis  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Visual impairment  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Retinal artery occlusion  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Retinal haemorrhage  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Scleral thinning  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  1/167 (0.60%)  1 2/248 (0.81%)  2
Pancreatitis  1  1/167 (0.60%)  1 3/248 (1.21%)  3
Hiatus hernia  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Mesenteric vein thrombosis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Small intestinal obstruction  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Vomiting  1  0/167 (0.00%)  0 1/248 (0.40%)  1
General disorders     
Asthenia  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Chest pain  1  3/167 (1.80%)  3 0/248 (0.00%)  0
Death  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Mucosal inflammation  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Non-cardiac chest pain  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Systemic inflammatory response syndrome  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Hepatobiliary disorders     
Cholecystitis  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Cholelithiasis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Portal vein thrombosis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Cholecystitis acute  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Gallbladder rupture  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Infections and infestations     
Endophthalmitis  1  1/167 (0.60%)  1 4/248 (1.61%)  5
Pneumonia  1  1/167 (0.60%)  1 7/248 (2.82%)  7
Sepsis  1  2/167 (1.20%)  2 3/248 (1.21%)  3
Urinary tract infection  1  1/167 (0.60%)  1 6/248 (2.42%)  6
Diverticulitis  1  0/167 (0.00%)  0 2/248 (0.81%)  2
Cellulitis  1  2/167 (1.20%)  2 0/248 (0.00%)  0
Arthritis infective  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Bacteraemia  1  1/167 (0.60%)  1 0/248 (0.00%)  0
COVID-19  1  0/167 (0.00%)  0 1/248 (0.40%)  1
COVID-19 pneumonia  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Influenza  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Kidney infection  1  1/167 (0.60%)  2 0/248 (0.00%)  0
Metapneumovirus pneumonia  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Pneumonia bacterial  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Post procedural infection  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Septic arthritis staphylococcal  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Septic shock  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Injury, poisoning and procedural complications     
Conjunctival retraction  1  0/167 (0.00%)  0 3/248 (1.21%)  3
Facial bones fracture  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Acetabulum fracture  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Contusion  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Hip fracture  1  0/167 (0.00%)  0 2/248 (0.81%)  2
Overdose  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Rib fracture  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Road traffic accident  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Metabolism and nutrition disorders     
Dehydration  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Hyponatraemia  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Lactic acidosis  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  0/167 (0.00%)  0 3/248 (1.21%)  4
Rhabdomyolysis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Rotator cuff syndrome  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Arthralgia  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Muscular weakness  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Non-small cell lung cancer  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Pancreatic carcinoma  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Pancreatic carcinoma stage I  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Penile squamous cell carcinoma  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Skin cancer  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Small intestine adenocarcinoma  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Squamous cell carcinoma of pharynx  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Colon cancer metastatic  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Endometrial adenocarcinoma  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Hepatic cancer  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Nervous system disorders     
Cerebrovascular accident  1  1/167 (0.60%)  1 4/248 (1.61%)  4
Syncope  1  3/167 (1.80%)  3 0/248 (0.00%)  0
Disturbance in attention  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Dizziness  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Ischaemic stroke  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Parkinson's disease  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Temporal lobe epilepsy  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Transient ischaemic attack  1  0/167 (0.00%)  0 2/248 (0.81%)  2
Product Issues     
Device dislocation  1  0/167 (0.00%)  0 3/248 (1.21%)  3
Renal and urinary disorders     
Acute kidney injury  1  1/167 (0.60%)  1 1/248 (0.40%)  1
Nephrolithiasis  1  0/167 (0.00%)  0 2/248 (0.81%)  2
Renal embolism  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Renal infarct  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Ureterolithiasis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Reproductive system and breast disorders     
Prostatitis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Prostatomegaly  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/167 (0.60%)  1 3/248 (1.21%)  3
Chronic obstructive pulmonary disease  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Surgical and medical procedures     
Hip arthroplasty  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Vascular disorders     
Aortic stenosis  1  1/167 (0.60%)  1 0/248 (0.00%)  0
Haematoma  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Hypertension  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Hypotension  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Aortic aneurysm  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Arteriosclerosis  1  0/167 (0.00%)  0 1/248 (0.40%)  1
Thrombosis  1  0/167 (0.00%)  0 1/248 (0.40%)  1
1
Term from vocabulary, MedDRA v23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intravitreal Arm PDS Implant Arm
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   58/167 (34.73%)      225/248 (90.73%)    
Eye disorders     
Conjunctival haemorrhage  1  12/167 (7.19%)  14 178/248 (71.77%)  193
Conjunctival hyperaemia  1  3/167 (1.80%)  4 66/248 (26.61%)  71
Iritis  1  1/167 (0.60%)  1 50/248 (20.16%)  55
Eye pain  1  8/167 (4.79%)  8 25/248 (10.08%)  28
Vitreous floaters  1  4/167 (2.40%)  4 23/248 (9.27%)  24
Vitreous detachment  1  8/167 (4.79%)  11 17/248 (6.85%)  19
Punctate keratitis  1  4/167 (2.40%)  6 17/248 (6.85%)  25
Vitreous haemorrhage  1  3/167 (1.80%)  4 13/248 (5.24%)  14
Neovascular age-related macular degeneration  1  15/167 (8.98%)  15 20/248 (8.06%)  20
Foreign body sensation in eyes  1  2/167 (1.20%)  2 18/248 (7.26%)  20
Hypotony of eye  1  0/167 (0.00%)  0 15/248 (6.05%)  15
Conjunctival bleb  1  0/167 (0.00%)  0 16/248 (6.45%)  16
Infections and infestations     
Nasopharyngitis  1  14/167 (8.38%)  15 13/248 (5.24%)  14
Nervous system disorders     
Headache  1  4/167 (2.40%)  4 14/248 (5.65%)  14
1
Term from vocabulary, MedDRA v23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
EMail: global-roche-genentech-trials@gene.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03677934    
Other Study ID Numbers: GR40548
First Submitted: September 11, 2018
First Posted: September 19, 2018
Results First Submitted: November 18, 2021
Results First Posted: March 25, 2022
Last Update Posted: October 4, 2022