Anti-angiOpoeitin 2 Plus Anti-vascular eNdothelial Growth Factor as a therapY for Neovascular Age Related Macular Degeneration: Evaluation of a fiXed Combination Intravitreal Injection (ONYX)

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ClinicalTrials.gov Identifier: NCT02713204

Recruitment Status : Completed

First Posted : March 18, 2016

Results First Posted : May 7, 2019

Last Update Posted : May 7, 2019

Sponsor:

Information provided by (Responsible Party):

Regeneron Pharmaceuticals

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Neovascular Age-Related Macular Degeneration
Interventions	Drug: REGN910-3 Drug: Intravitreal Aflibercept Injection (IAI)
Enrollment	365

Participant Flow

Recruitment Details	The study was conducted at 87 sites in the United States. A total of 560 participants were screened in the study.
Pre-assignment Details	Out of 560 participants, 365 were randomized & treated. Participants were randomized in 1:2:3 to receive REGN910-3 3:2mg, REGN910-3 6:2mg & 2mg intravitreal aflibercept injection (IAI) followed by re-randomization at week 12 in REGN910-3 6:2mg & IAI 2mg arm. Not all participants who completed Week 12 were re-randomized & continued to Week 36.


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept 2 mg	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8	Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12	Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description	Participants were administered intravitreal injection of REGN910-3 (3 milligram [mg]:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive IAI Q8 beginning at week 16 through week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Period Title: Baseline (Day 1) up to Week 12
Started	60	122	183	0	0	0	0	0
Completed	59	121	181	0	0	0	0	0
Not Completed	1	1	2	0	0	0	0	0
Reason Not Completed
Adverse Event	1	0	1	0	0	0	0	0
Withdrawal by Subject	0	0	1	0	0	0	0	0
Lost to Follow-up	0	1	0	0	0	0	0	0
Period Title: From Week 12 up to Week 36
Started	58	0	0	57	62	60	62	58
Completed	57	0	0	53	60	59	60	54
Not Completed	1	0	0	4	2	1	2	4
Reason Not Completed
Adverse Event	1	0	0	1	1	0	2	1
Death	0	0	0	1	0	1	0	3
Lost to Follow-up	0	0	0	2	0	0	0	0
Participant Re-located	0	0	0	0	1	0	0	0

Baseline Characteristics

Arm/Group Title		REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept (IAI) 2 mg	Total
Arm/Group Description		Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Total of all reporting groups
Arm/Group Description		Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 16 or Week 20 and Q8 or Q12 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Total of all reporting groups
Overall Number of Baseline Participants		59	122	183	364
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	59 participants	122 participants	183 participants	364 participants
		79.2 (9.37)	79.4 (8.91)	78.4 (8.37)	78.9 (8.71)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	59 participants	122 participants	183 participants	364 participants
	Female	41 69.5%	75 61.5%	110 60.1%	226 62.1%
	Male	18 30.5%	47 38.5%	73 39.9%	138 37.9%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	59 participants	122 participants	183 participants	364 participants
	Hispanic or Latino	2 3.4%	7 5.7%	9 4.9%	18 4.9%
	Not Hispanic or Latino	57 96.6%	115 94.3%	174 95.1%	346 95.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	59 participants	122 participants	183 participants	364 participants
White		58	116	178	352
Black or African American		0	1	1	2
Asian		1	3	2	6
American Indian or Alaska Native		0	1	0	1
Native Hawaiian or Other Pacific Islander		0	1	0	1
Other		0	0	2	2

Outcome Measures

1.Primary Outcome


Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12
Description	Visual function of the study eye was assessed using the Early Treatmen...
Description	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Best Corrected Visual Acuity (BCVA) score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received any study drug, had baseline measurement of BCVA & at least 1 post-baseline assessment of BCVA. Last observation carried forward (LOCF) method was used to impute missing data. Here "Overall Number of Participants Analyzed" = Participants who were evaluable for this outcome measure.


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept (IAI) 2 mg
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	59	122	183
Mean (Standard Deviation) Unit of Measure: Letters correctly read
	5.2 (10.51)	5.6 (10.59)	5.4 (9.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.

Statistical Test of Hypothesis	P-Value	0.9894
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95% -2.99 to 3.03
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8346
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95% -2.09 to 2.59
	Estimation Comments	[Not Specified]

2.Primary Outcome


Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36
Description	Visual function of the study eye was assessed using the Early Treatmen...
Description	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 36.
Time Frame	At Week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12	Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	57	62	60	62	58
Mean (Standard Deviation) Unit of Measure: Letters correctly read
	5.9 (11.95)	6.0 (12.00)	6.4 (12.24)	6.9 (12.49)	4.2 (12.50)	2.9 (12.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4611
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.20
	Confidence Interval	(2-Sided) 95% -4.41 to 2.00
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	Threshold for significance at 0.05 level.

Statistical Test of Hypothesis	P-Value	0.2225
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95% -5.22 to 1.22
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6063
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95% -3.97 to 2.32
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0426
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-3.25
	Confidence Interval	(2-Sided) 95% -6.39 to -0.11
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0073
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-4.39
	Confidence Interval	(2-Sided) 95% -7.58 to -1.19
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4690
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95% -2.01 to 4.36
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1267
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95% -0.69 to 5.54
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12
Description	Central Sub-field Retinal Thickness (CST) was assessed using Spectral ...
Description	Central Sub-field Retinal Thickness (CST) was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from last observation carried forward (LOCF) post-baseline value at Week 12.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept (IAI) 2 mg
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	59	122	182
Mean (Standard Deviation) Unit of Measure: Microns
	-182.2 (172.73)	-200.0 (152.82)	-178.6 (138.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4130
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-11.57
	Confidence Interval	(2-Sided) 95% -39.5 to 16.20
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6587
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-4.88
	Confidence Interval	(2-Sided) 95% -26.2 to 16.85
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36
Description	CST was assessed using spectral domain optical coherence tomography (S...
Description	CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 36.
Time Frame	At Week 36

Outcome Measure Data

Analysis Population Description

FAS secondary randomization set was used. Here "Overall Number of Participants Analyzed"= Participants who were evaluable for this endpoint.


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12	Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	57	62	59	62	58
Mean (Standard Deviation) Unit of Measure: Microns
	-174.6 (165.22)	-216.6 (187.40)	-181.3 (148.71)	-198.4 (155.72)	-169.7 (129.74)	-187.3 (161.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3833
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	17.04
	Confidence Interval	(2-Sided) 95% -21.35 to 55.43
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5141
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	12.85
	Confidence Interval	(2-Sided) 95% -25.84 to 51.53
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0785
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	33.89
	Confidence Interval	(2-Sided) 95% -3.89 to 71.67
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0281
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	42.27
	Confidence Interval	(2-Sided) 95% 4.56 to 79.98
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3934
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	16.65
	Confidence Interval	(2-Sided) 95% -21.67 to 54.96
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2790
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	21.05
	Confidence Interval	(2-Sided) 95% -17.13 to 59.22
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6586
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-8.38
	Confidence Interval	(2-Sided) 95% -45.64 to 28.88
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12
Description	Choroidal neovascularization (CNV) was evaluated using fluorescein ang...
Description	Choroidal neovascularization (CNV) was evaluated using fluorescein angiography (FA).CNV area values measured in square millimeters (mm^2); lower values represent better outcomes.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept (IAI) 2 mg
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	115	171
Mean (Standard Deviation) Unit of Measure: mm^2
	-2.2 (5.59)	-3.5 (5.34)	-3.7 (6.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4889
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95% -1.01 to 2.10
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7027
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95% -0.99 to 1.46
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36
Description	Choroidal neovascularization (CNV) was evaluated using fluorescein ang...
Description	Choroidal neovascularization (CNV) was evaluated using fluorescein angiography (FA).CNV area values measured in square millimeters (mm^2); lower values represent better outcomes.
Time Frame	At Week 36

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12	Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 beginning at Week 16 through Week 32	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	56	62	59	62	58
Mean (Standard Deviation) Unit of Measure: mm^2
	-3.7 (5.04)	-4.1 (6.09)	-4.9 (5.58)	-4.3 (6.55)	-5.1 (5.60)	-5.3 (5.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4927
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95% -2.34 to 1.13
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6645
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95% -1.36 to 2.13
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3091
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95% -2.61 to 0.83
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4898
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95% -2.29 to 1.10
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3504
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95% -2.50 to 0.89
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2632
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95% -2.70 to 0.74
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8056
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95% -1.46 to 1.88
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Change From Baseline in Total Lesion Area at Week 12
Description	Total lesion area was evaluated using fluorescein angiography (FA). Le...
Description	Total lesion area was evaluated using fluorescein angiography (FA). Lesion area values measured in square millimeters (mm^2); lower values represent better outcomes.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept (IAI) 2 mg
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	115	171
Mean (Standard Deviation) Unit of Measure: mm^2
	-2.0 (6.10)	-3.5 (5.45)	-3.4 (6.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5065
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95% -1.11 to 2.25
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7418
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95% -1.55 to 1.10
	Estimation Comments	[Not Specified]

8.Secondary Outcome


Title	Change From Baseline in Total Lesion Area at Week 36
Description	Total lesion area was evaluated using fluorescein angiography (FA). Le...
Description	Total lesion area was evaluated using fluorescein angiography (FA). Lesion area values measured in square millimeters (mm^2); lower values represent better outcomes.
Time Frame	At Week 36

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12	Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	56	62	59	62	58
Mean (Standard Deviation) Unit of Measure: mm^2
	-3.0 (5.91)	-3.9 (5.79)	-4.7 (5.35)	-3.9 (6.67)	-4.7 (5.43)	-5.3 (5.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (3 mg:2 mg), Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8383
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95% -1.99 to 1.62
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.9180
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95% -1.91 to 1.72
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1238
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.41
	Confidence Interval	(2-Sided) 95% -3.20 to 0.39
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2819
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95% -2.73 to 0.80
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2581
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95% -2.78 to 0.75
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8, REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3390
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95% -2.66 to 0.92
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.9558
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95% -1.69 to 1.79
	Estimation Comments	[Not Specified]

9.Other Pre-specified Outcome


Title	Proportion of Participants With No Retinal and/or Subretinal Fluid at Week 12
Description	Retinal and/or subretinal fluid was assessed using intraretinal fluid ...
Description	Retinal and/or subretinal fluid was assessed using intraretinal fluid (IRF) cystoid edema and subretinal fluid (SRF) in the center subfield on optical coherence tomography (OCT). If answers were "no" to both measurements, there was no retinal and/or subretinal fluid (Dry); if "yes" to any of the 2 measurements, there was retinal and/or subretinal fluid (Not Dry); other than the previous 2 cases, retinal and/or subretinal fluid was undetermined.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg)	Aflibercept (IAI) 2 mg
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	57	122	179
Measure Type: Number Unit of Measure: Proportion of participants
	0.49	0.51	0.44

10.Other Pre-specified Outcome


Title	Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36
Description	Retinal and/or subretinal fluid was assessed using intraretinal fluid ...
Description	Retinal and/or subretinal fluid was assessed using intraretinal fluid (IRF) cystoid edema and subretinal fluid (SRF) in the center subfield on OCT. If answers were "no" to both measurements, there was no retinal and/or subretinal fluid (Dry); if "yes" to any of the 2 measurements, there was retinal and/or subretinal fluid (Not Dry); other than the previous 2 cases, retinal and/or subretinal fluid was undetermined.
Time Frame	Baseline through Week 36

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12	Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	57	57	62	59	62	55
Measure Type: Number Unit of Measure: Proportion of participants
	0.54	0.49	0.53	0.42	0.53	0.47

11.Other Pre-specified Outcome


Title	Time to No Retinal and/or Subretinal Fluid Through Week 36
Description	Kaplan-Meier estimated time to no retinal and/or subretinal fluid thro...
Description	Kaplan-Meier estimated time to no retinal and/or subretinal fluid through week 36 (days). Retinal and/or subretinal fluid was assessed using intraretinal fluid (IRF) cystoid edema and subretinal fluid (SRF). If answers were "no" to both measurements, there was no retinal and/or subretinal fluid (Dry); if "yes" to any of the 2 measurements, there was retinal and/or subretinal fluid (Not Dry); other than the previous 2 cases, retinal and/or subretinal fluid was undetermined.
Time Frame	Baseline through Week 36

Outcome Measure Data

Analysis Population Description


Arm/Group Title	REGN910-3 (3 mg:2 mg)	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8	REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q8	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12	Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm/Group Description:	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...	Participants were administered intr...
Arm/Group Description:	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 beginning at Week 16 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q12 beginning at Week 20 through Week 32.	Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.
Overall Number of Participants Analyzed	58	57	62	60	62	58
Mean (Standard Error) Unit of Measure: Days
	105.6 (11.06)	80.9 (9.02)	84.9 (8.01)	106.4 (11.04)	96.5 (11.27)	107.1 (10.05)

Adverse Events

Time Frame	Timeframe for AE reporting
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that are AEs that developed/worsened during the study (Baseline through Week 36).

Arm/Group Title	REGN910-3 3 mg:2 mg		REGN910-3 6 mg:2 mg		IAI 2 mg		IAI 2mg to REGN910-3
Arm/Group Description	Participants were administered intr...		Participants were administered intr...		Participants were administered intr...		Participants were administered intr...
Arm/Group Description	Participants were administered intravitreal injection of REGN910-3 (3 mg:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 through Week 32.		Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32.		Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32.		Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32. Data in this arm include only the 58 participants that switched to high dose at week 16. Data from these 58 participants are also included in the Aflibercept (IAI) 2 mg arm (n = 183).
All-Cause Mortality
	REGN910-3 3 mg:2 mg		REGN910-3 6 mg:2 mg		IAI 2 mg		IAI 2mg to REGN910-3
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	1/60 (1.67%)		2/122 (1.64%)		7/183 (3.83%)		3/58 (5.17%)
Serious Adverse Events Serious Adverse Events
	REGN910-3 3 mg:2 mg		REGN910-3 6 mg:2 mg		IAI 2 mg		IAI 2mg to REGN910-3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/60 (18.33%)		20/122 (16.39%)		30/183 (16.39%)		8/58 (13.79%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Cardiac disorders
Acute myocardial infarction ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	2/183 (1.09%)	2	0/58 (0.00%)	0
Atrioventricular block ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Cardiac failure ^† 1	1/60 (1.67%)	1	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Cardiac failure congestive ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Cardio-Respiratory arrest ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Coronary artery disease ^† 1	1/60 (1.67%)	1	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Pericardial effusion ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Supraventricular tachycardia ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Ear and labyrinth disorders
Vertigo ^† 1	1/60 (1.67%)	1	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Eye disorders
Corneal oedema ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Dry age-related macular degeneration ^† 1	1/60 (1.67%)	1	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Iritis ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Macular hole ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Retinal degeneration ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Retinal detachment ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Visual acuity reduced ^† 1	1/60 (1.67%)	1	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Gastrointestinal disorders
Ascites ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Intestinal mass ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
General disorders
Chest pain ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Infections and infestations
Arthritis infective ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Cellulitis ^† 1	2/60 (3.33%)	2	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Diverticulitis intestinal haemorrhagic ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Endophthalmitis ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Escherichia sepsis ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Medical device site joint infection ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Pneumonia ^† 1	3/60 (5.00%)	3	0/122 (0.00%)	0	2/183 (1.09%)	2	0/58 (0.00%)	0
Sepsis ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	2/183 (1.09%)	2	0/58 (0.00%)	0
Staphylococcal infection ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Urosepsis ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Injury, poisoning and procedural complications
Eschar ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Fall ^† 1	1/60 (1.67%)	1	2/122 (1.64%)	2	1/183 (0.55%)	2	0/58 (0.00%)	0
Femoral neck fracture ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Hip fracture ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	2/183 (1.09%)	2	1/58 (1.72%)	1
Pelvic fracture ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Rib fracture ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	2/183 (1.09%)	2	0/58 (0.00%)	0
Sternal fracture ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Metabolism and nutrition disorders
Hypoglycaemia ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	1/183 (0.55%)	1	1/58 (1.72%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	1/60 (1.67%)	1	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Breast cancer ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Invasive ductal breast carcinoma ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Lung adenocarcinoma stage iv ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Metastases to bone ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	2/183 (1.09%)	2	1/58 (1.72%)	1
Metastases to liver ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Oesophageal adenocarcinoma ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Prostate cancer metastatic ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Nervous system disorders
Carotid arteriosclerosis ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Cerebral infarction ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Cerebrovascular accident ^† 1	0/60 (0.00%)	0	2/122 (1.64%)	2	1/183 (0.55%)	1	0/58 (0.00%)	0
Ischaemic stroke ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Presyncope ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Transient ischaemic attack ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	1/183 (0.55%)	1	1/58 (1.72%)	1
Calculus bladder ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
Chronic kidney disease ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	2/183 (1.09%)	2	1/58 (1.72%)	1
Reproductive system and breast disorders
Genital prolapse ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease ^† 1	0/60 (0.00%)	0	2/122 (1.64%)	2	1/183 (0.55%)	1	0/58 (0.00%)	0
Pleural effusion ^† 1	1/60 (1.67%)	1	0/122 (0.00%)	0	0/183 (0.00%)	0	0/58 (0.00%)	0
Pulmonary fibrosis ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Vascular disorders
Aortic stenosis ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	1/58 (1.72%)	1
Hypertension ^† 1	0/60 (0.00%)	0	1/122 (0.82%)	1	0/183 (0.00%)	0	0/58 (0.00%)	0
Orthostatic hypotension ^† 1	0/60 (0.00%)	0	0/122 (0.00%)	0	1/183 (0.55%)	1	0/58 (0.00%)	0
1 Term from vocabulary, MedDRA (20.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	REGN910-3 3 mg:2 mg		REGN910-3 6 mg:2 mg		IAI 2 mg		IAI 2mg to REGN910-3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/60 (28.33%)		41/122 (33.61%)		51/183 (27.87%)		20/58 (34.48%)
Cardiac disorders
Atrial fibrillation ^† 1	3/60 (5.00%)	3	2/122 (1.64%)	2	4/183 (2.19%)	5	1/58 (1.72%)	2
Eye disorders
Dry eye ^† 1	2/60 (3.33%)	2	7/122 (5.74%)	8	4/183 (2.19%)	4	1/58 (1.72%)	1
Neovascular age-related macular degeneration ^† 1	4/60 (6.67%)	4	5/122 (4.10%)	5	5/183 (2.73%)	5	0/58 (0.00%)	0
Retinal haemorrhage ^† 1	0/60 (0.00%)	0	2/122 (1.64%)	2	12/183 (6.56%)	14	6/58 (10.34%)	7
Vitreous detachment ^† 1	3/60 (5.00%)	4	7/122 (5.74%)	7	4/183 (2.19%)	4	1/58 (1.72%)	1
Infections and infestations
Upper respiratory tract infection ^† 1	4/60 (6.67%)	4	2/122 (1.64%)	2	3/183 (1.64%)	3	2/58 (3.45%)	2
Urinary tract infection ^† 1	0/60 (0.00%)	0	7/122 (5.74%)	7	6/183 (3.28%)	7	1/58 (1.72%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis ^† 1	1/60 (1.67%)	1	1/122 (0.82%)	1	3/183 (1.64%)	3	3/58 (5.17%)	3
Vascular disorders
Hypertension ^† 1	4/60 (6.67%)	4	13/122 (10.66%)	15	17/183 (9.29%)	18	8/58 (13.79%)	9
1 Term from vocabulary, MedDRA (20.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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 investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Clinical Trial Management
Organization:	Regeneron Pharmaceuticals
Phone:	844-734-6643
EMail:	clinicaltrials@regeneron.com

Layout table for additonal information

Responsible Party:	Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02713204
Other Study ID Numbers:	R910-3-AMD-1517
First Submitted:	March 14, 2016
First Posted:	March 18, 2016
Results First Submitted:	October 3, 2018
Results First Posted:	May 7, 2019
Last Update Posted:	May 7, 2019

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