ONYX: 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

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02713204
• Collaborator: (none)
• Enrollment: 365
• Locations: 87
• Arms: 3
• Actual Duration (Months): 18.1
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of the study is to compare the efficacy of intravitreal (IVT)-administered REGN910-3 compared to intravitreal aflibercept injection (IAI).

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-Related Macular Degeneration	Drug: REGN910-3; Drug: Intravitreal Aflibercept Injection (IAI)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 365 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Masked, Active-Controlled Phase 2 Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal REGN910-3 in Patients With Neovascular Age-Related Macular Degeneration
• Actual Study Start Date: Mar 31, 2016
• Actual Primary Completion Date: Oct 3, 2017
• Actual Study Completion Date: Oct 3, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: REGN910-3 (3 mg: 2 mg) 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 up to Week 32.	Drug: REGN910-3
Experimental: REGN910-3 (6 mg:2 mg) 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.	Drug: REGN910-3
Experimental: Aflibercept (IAI) 2 mg 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.	Drug: REGN910-3; Drug: Intravitreal Aflibercept Injection (IAI); Other Names: EYLEA® (aflibercept) Injection BAY86-5321

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 [At Week 12]

   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.

2. Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 [At Week 36]

   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.

Secondary Outcome Measures

1. Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 [At Week 12]

   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.

2. Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 [At Week 36]

   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.

3. Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 [At Week 12]

   Choroidal neovascularization (CNV) was evaluated using fluorescein angiography (FA).CNV area values measured in square millimeters (mm^2); lower values represent better outcomes.

4. Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 [At Week 36]

   Choroidal neovascularization (CNV) was evaluated using fluorescein angiography (FA).CNV area values measured in square millimeters (mm^2); lower values represent better outcomes.

5. Change From Baseline in Total Lesion Area at Week 12 [At Week 12]

   Total lesion area was evaluated using fluorescein angiography (FA). Lesion area values measured in square millimeters (mm^2); lower values represent better outcomes.

6. Change From Baseline in Total Lesion Area at Week 36 [At Week 36]

   Total lesion area was evaluated using fluorescein angiography (FA). Lesion area values measured in square millimeters (mm^2); lower values represent better outcomes.

Other Outcome Measures

1. Proportion of Participants With No Retinal and/or Subretinal Fluid at Week 12 [At Week 12]

   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.

2. Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 [Baseline through Week 36]

   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.

3. Time to No Retinal and/or Subretinal Fluid Through Week 36 [Baseline through Week 36]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Men or women ≥50 years of age with active subfoveal CNV secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye as assessed by a central reading center

2. BCVA ETDRS letter score of 73 to 24 (Snellen equivalent of 20/40 to 20/320) in the study eye.

3. Willing and able to comply with clinic visits and study-related procedures.

4. Provide signed informed consent.

Key Exclusion Criteria:

1. Evidence of CNV due to any cause other than AMD in either eye

2. Prior IVT anti-VEGF in the study eye

3. Evidence of DME or diabetic retinopathy (defined as more than 1 microaneurysm) in either eye in diabetic patients

4. Any history of macular hole of stage 2 and above in the study eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regeneron Investigational Site	Mobile	Alabama	United States
2	Regeneron Investigational Site 1	Phoenix	Arizona	United States
3	Regeneron Investigational Site 2	Phoenix	Arizona	United States
4	Regeneron Investigational Site 3	Phoenix	Arizona	United States
5	Regeneron Investigational Site 1	Tucson	Arizona	United States
6	Regeneron Investigational Site 2	Tucson	Arizona	United States
7	Regeneron Investigational Site	Arcadia	California	United States
8	Regeneron Investigational Site	Bakersfield	California	United States
9	Regeneron Investigational Site	Beverly Hills	California	United States
10	Regeneron Investigational Site	Encino	California	United States
11	Regeneron Investigational Site 1	Los Angeles	California	United States
12	Regeneron Investigational Site 2	Los Angeles	California	United States
13	Regeneron Investigational Site	Mountain View	California	United States
14	Regeneron Investigational Site	Oceanside	California	United States
15	Regeneron Investigational Site 1	Palm Desert	California	United States
16	Regeneron Investigational Site 2	Palm Desert	California	United States
17	Regeneron Investigational Site	Palo Alto	California	United States
18	Regeneron Investigational Site	Poway	California	United States
19	Regeneron Investigational Site	Redlands	California	United States
20	Regeneron Investigational Site	Sacramento	California	United States
21	Regeneron Investigational Site	Santa Maria	California	United States
22	Regeneron Investigational Site	New London	Connecticut	United States
23	Regeneron Investigational Site	Altamonte Springs	Florida	United States
24	Regeneron Investigational Site	Fort Lauderdale	Florida	United States
25	Regeneron Investigational Site	Lakeland	Florida	United States
26	Regeneron Investigational Site	Largo	Florida	United States
27	Regeneron Investigational Site	Miami	Florida	United States
28	Regeneron Investigational Site	Naples	Florida	United States
29	Regeneron Investigational Site	Palm Beach	Florida	United States
30	Regeneron Investigational Site	Tallahassee	Florida	United States
31	Regeneron Investigational Site	Winter Haven	Florida	United States
32	Regeneron Investigational Site	Augusta	Georgia	United States
33	Regeneron Investigational Site	Decatur	Georgia	United States
34	Regeneron Investigational Site	'Aiea	Hawaii	United States
35	Regeneron Investigational Site 1	Chicago	Illinois	United States
36	Regeneron Investigational Site 2	Chicago	Illinois	United States
37	Regeneron Investigational Site	Lemont	Illinois	United States
38	Regeneron Investigational Site	Oak Forest	Illinois	United States
39	Regeneron Investigational Site	Oak Park	Illinois	United States
40	Regeneron Investigational Site	Urbana	Illinois	United States
41	Regeneron Investigational Site	New Albany	Indiana	United States
42	Regeneron Investigational Site	Des Moines	Iowa	United States
43	Regeneron Investigational Site	Metairie	Louisiana	United States
44	Regeneron Investigational Site 1	Baltimore	Maryland	United States
45	Regeneron Investigational Site 2	Baltimore	Maryland	United States
46	Regeneron Investigational Site	Chevy Chase	Maryland	United States
47	Regeneron Investigational Site 1	Boston	Massachusetts	United States
48	Regeneron Investigational Site 2	Boston	Massachusetts	United States
49	Regeneron Investigational Site	Jackson	Michigan	United States
50	Regeneron Investigational Site	Minneapolis	Minnesota	United States
51	Regeneron Investigational Site	Saint Louis	Missouri	United States
52	Regeneron Investigational Site	Las Vegas	Nevada	United States
53	Regeneron Investigational Site	Portsmouth	New Hampshire	United States
54	Regeneron Investigational Site	Edison	New Jersey	United States
55	Regeneron Investigational Site	Teaneck	New Jersey	United States
56	Regeneron Investigational Site	Albuquerque	New Mexico	United States
57	Regeneron Investigational Site	Albany	New York	United States
58	Regeneron Investigational Site	Bloomfield	New York	United States
59	Regeneron Investigational Site	Great Neck	New York	United States
60	Regeneron Investigational Site	Hauppauge	New York	United States
61	Regeneron Investigational Site	Rochester	New York	United States
62	Regeneron Investigational Site	Syracuse	New York	United States
63	Regeneron Investigational Site	Asheville	North Carolina	United States
64	Regeneron Investigational Site	Charlotte	North Carolina	United States
65	Regeneron Investigational Site	Durham	North Carolina	United States
66	Regeneron Investigational Site	Cleveland	Ohio	United States
67	Regeneron Investigational Site	Dublin	Ohio	United States
68	Regeneron Investigational Site	Portland	Oregon	United States
69	Regeneron Investigational Site	Camp Hill	Pennsylvania	United States
70	Regeneron Investigational Site	Huntingdon	Pennsylvania	United States
71	Regeneron Investigational Site	Ladson	South Carolina	United States
72	Regeneron Investigational Site	Rapid City	South Dakota	United States
73	Regeneron Investigational Site	Germantown	Tennessee	United States
74	Regeneron Investigational Site	Knoxville	Tennessee	United States
75	Regeneron Investigational Site	Nashville	Tennessee	United States
76	Regeneron Investigational Site	Abilene	Texas	United States
77	Regeneron Investigational Site 1	Austin	Texas	United States
78	Regeneron Investigational Site 2	Austin	Texas	United States
79	Regeneron Investigational Site	Dallas	Texas	United States
80	Regeneron Investigational Site 1	Fort Worth	Texas	United States
81	Regeneron Investigational Site 2	Fort Worth	Texas	United States
82	Regeneron Investigational Site	Harlingen	Texas	United States
83	Regeneron Investigational Site	Houston	Texas	United States
84	Regeneron Investigational Site	The Woodlands	Texas	United States
85	Regeneron Investigational Site	Willow Park	Texas	United States
86	Regeneron Investigational Site	Salt Lake City	Utah	United States
87	Regeneron Investigational Site	Madison	Wisconsin	United States

Sponsors and Collaborators

• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - May 31, 2017
• Statistical Analysis Plan - Oct 19, 2017

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02713204
• Other Study ID Numbers: R910-3-AMD-1517
• First Posted: Mar 18, 2016
• Last Update Posted: May 7, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Macular Degeneration; Wet Macular Degeneration; Aflibercept

Study Results

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 Detail	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 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
Period Title: Baseline (Day 1) up to Week 12
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

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 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 Participants	59	122	183	364
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	79.2 (9.37)	79.4 (8.91)	78.4 (8.37)	78.9 (8.71)
Sex: Female, Male (Count of 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) (Count of 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%
Race/Ethnicity, Customized (Number) [Number]
White	58 98.3%	116 95.1%	178 97.3%	352 96.7%
Black or African American	0 0%	1 0.8%	1 0.5%	2 0.5%
Asian	1 1.7%	3 2.5%	2 1.1%	6 1.6%
American Indian or Alaska Native	0 0%	1 0.8%	0 0%	1 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.8%	0 0%	1 0.3%
Other	0 0%	0 0%	2 1.1%	2 0.5%

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 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 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.
Measure Participants	59	122	183
Mean (Standard Deviation) [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
	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
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -2.99 to 3.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.8346
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95%; -2.09 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 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.
Measure Participants	58	57	62	60	62	58
Mean (Standard Deviation) [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
Statistical Test of Hypothesis	p-Value	0.4611
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.20
	Confidence Interval	(2-Sided) 95%; -4.41 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 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	Threshold for significance at 0.05 level.
Statistical Test of Hypothesis	p-Value	0.2225
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -5.22 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 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
Statistical Test of Hypothesis	p-Value	0.6063
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95%; -3.97 to 2.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0426
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-3.25
	Confidence Interval	(2-Sided) 95%; -6.39 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0073
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-4.39
	Confidence Interval	(2-Sided) 95%; -7.58 to -1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	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
Statistical Test of Hypothesis	p-Value	0.4690
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; -2.01 to 4.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg, 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
Statistical Test of Hypothesis	p-Value	0.1267
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95%; -0.69 to 5.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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

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 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.
Measure Participants	59	122	182
Mean (Standard Deviation) [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
Statistical Test of Hypothesis	p-Value	0.4130
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-11.57
	Confidence Interval	(2-Sided) 95%; -39.5 to 16.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.6587
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-4.88
	Confidence Interval	(2-Sided) 95%; -26.2 to 16.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 (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 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.
Measure Participants	58	57	62	59	62	58
Mean (Standard Deviation) [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 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
Statistical Test of Hypothesis	p-Value	0.3833
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	17.04
	Confidence Interval	(2-Sided) 95%; -21.35 to 55.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 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
Statistical Test of Hypothesis	p-Value	0.5141
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	12.85
	Confidence Interval	(2-Sided) 95%; -25.84 to 51.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 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
Statistical Test of Hypothesis	p-Value	0.0785
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	33.89
	Confidence Interval	(2-Sided) 95%; -3.89 to 71.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
Statistical Test of Hypothesis	p-Value	0.0281
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	42.27
	Confidence Interval	(2-Sided) 95%; 4.56 to 79.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3934
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	16.65
	Confidence Interval	(2-Sided) 95%; -21.67 to 54.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	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
Statistical Test of Hypothesis	p-Value	0.2790
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	21.05
	Confidence Interval	(2-Sided) 95%; -17.13 to 59.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg, 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
Statistical Test of Hypothesis	p-Value	0.6586
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-8.38
	Confidence Interval	(2-Sided) 95%; -45.64 to 28.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12
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

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 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.
Measure Participants	58	115	171
Mean (Standard Deviation) [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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4889
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; -1.01 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7027
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.99 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36
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

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) 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 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.
Measure Participants	58	56	62	59	62	58
Mean (Standard Deviation) [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 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4927
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.34 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6645
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; -1.36 to 2.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3091
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -2.61 to 0.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg, Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4898
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.29 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 Aflibercept (IAI) 2 mg Q12
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3504
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -2.50 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2632
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.98
	Confidence Interval	(2-Sided) 95%; -2.70 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg, Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8056
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -1.46 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Total Lesion Area at Week 12
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

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 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.
Measure Participants	58	115	171
Mean (Standard Deviation) [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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5065
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; -1.11 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7418
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -1.55 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Total Lesion Area at Week 36
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

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) 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 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.
Measure Participants	58	56	62	59	62	58
Mean (Standard Deviation) [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 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8383
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -1.99 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9180
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -1.91 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1238
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.41
	Confidence Interval	(2-Sided) 95%; -3.20 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg, Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2819
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -2.73 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 Aflibercept (IAI) 2 mg Q12
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2581
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -2.78 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	REGN910-3 (6 mg:2 mg), Aflibercept (IAI) 2 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3390
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -2.66 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9558
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -1.69 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 (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

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 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.
Measure Participants	57	122	179
Number [Proportion of participants]	0.49 0.8%	0.51 0.4%	0.44 0.2%

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 (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

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) 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 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.
Measure Participants	57	57	62	59	62	55
Number [Proportion of participants]	0.54 0.9%	0.49 0.4%	0.53 0.3%	0.42 0.1%	0.53 NaN	0.47 NaN

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 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

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) 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 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.
Measure Participants	58	57	62	60	62	58
Mean (Standard Error) [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 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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/60 (1.7%)		2/122 (1.6%)		7/183 (3.8%)		3/58 (5.2%)
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 (18.3%)		20/122 (16.4%)		30/183 (16.4%)		8/58 (13.8%)
Blood and lymphatic system disorders
Anaemia	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/60 (0%)	0	0/122 (0%)	0	2/183 (1.1%)	2	0/58 (0%)	0
Atrioventricular block	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Cardiac failure	1/60 (1.7%)	1	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Cardiac failure congestive	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Cardio-Respiratory arrest	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Coronary artery disease	1/60 (1.7%)	1	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Pericardial effusion	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Supraventricular tachycardia	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Ear and labyrinth disorders
Vertigo	1/60 (1.7%)	1	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Eye disorders
Corneal oedema	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Dry age-related macular degeneration	1/60 (1.7%)	1	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Iritis	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Macular hole	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Retinal degeneration	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Retinal detachment	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Visual acuity reduced	1/60 (1.7%)	1	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Gastrointestinal disorders
Ascites	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Intestinal mass	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
General disorders
Chest pain	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Infections and infestations
Arthritis infective	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Cellulitis	2/60 (3.3%)	2	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Diverticulitis intestinal haemorrhagic	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Endophthalmitis	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Escherichia sepsis	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Medical device site joint infection	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Pneumonia	3/60 (5%)	3	0/122 (0%)	0	2/183 (1.1%)	2	0/58 (0%)	0
Sepsis	0/60 (0%)	0	0/122 (0%)	0	2/183 (1.1%)	2	0/58 (0%)	0
Staphylococcal infection	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Urosepsis	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Injury, poisoning and procedural complications
Eschar	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Fall	1/60 (1.7%)	1	2/122 (1.6%)	2	1/183 (0.5%)	2	0/58 (0%)	0
Femoral neck fracture	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Hip fracture	0/60 (0%)	0	0/122 (0%)	0	2/183 (1.1%)	2	1/58 (1.7%)	1
Pelvic fracture	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Rib fracture	0/60 (0%)	0	1/122 (0.8%)	1	2/183 (1.1%)	2	0/58 (0%)	0
Sternal fracture	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/60 (0%)	0	1/122 (0.8%)	1	1/183 (0.5%)	1	1/58 (1.7%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/60 (1.7%)	1	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Breast cancer	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Invasive ductal breast carcinoma	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Lung adenocarcinoma stage iv	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Metastases to bone	0/60 (0%)	0	0/122 (0%)	0	2/183 (1.1%)	2	1/58 (1.7%)	1
Metastases to liver	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Oesophageal adenocarcinoma	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Prostate cancer metastatic	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Nervous system disorders
Carotid arteriosclerosis	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Cerebral infarction	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Cerebrovascular accident	0/60 (0%)	0	2/122 (1.6%)	2	1/183 (0.5%)	1	0/58 (0%)	0
Ischaemic stroke	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Presyncope	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Transient ischaemic attack	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/60 (0%)	0	1/122 (0.8%)	1	1/183 (0.5%)	1	1/58 (1.7%)	1
Calculus bladder	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Chronic kidney disease	0/60 (0%)	0	0/122 (0%)	0	2/183 (1.1%)	2	1/58 (1.7%)	1
Reproductive system and breast disorders
Genital prolapse	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/60 (0%)	0	2/122 (1.6%)	2	1/183 (0.5%)	1	0/58 (0%)	0
Pleural effusion	1/60 (1.7%)	1	0/122 (0%)	0	0/183 (0%)	0	0/58 (0%)	0
Pulmonary fibrosis	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Vascular disorders
Aortic stenosis	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	1/58 (1.7%)	1
Hypertension	0/60 (0%)	0	1/122 (0.8%)	1	0/183 (0%)	0	0/58 (0%)	0
Orthostatic hypotension	0/60 (0%)	0	0/122 (0%)	0	1/183 (0.5%)	1	0/58 (0%)	0
Other (Not Including 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	17/60 (28.3%)		41/122 (33.6%)		51/183 (27.9%)		20/58 (34.5%)
Cardiac disorders
Atrial fibrillation	3/60 (5%)	3	2/122 (1.6%)	2	4/183 (2.2%)	5	1/58 (1.7%)	2
Eye disorders
Dry eye	2/60 (3.3%)	2	7/122 (5.7%)	8	4/183 (2.2%)	4	1/58 (1.7%)	1
Neovascular age-related macular degeneration	4/60 (6.7%)	4	5/122 (4.1%)	5	5/183 (2.7%)	5	0/58 (0%)	0
Retinal haemorrhage	0/60 (0%)	0	2/122 (1.6%)	2	12/183 (6.6%)	14	6/58 (10.3%)	7
Vitreous detachment	3/60 (5%)	4	7/122 (5.7%)	7	4/183 (2.2%)	4	1/58 (1.7%)	1
Infections and infestations
Upper respiratory tract infection	4/60 (6.7%)	4	2/122 (1.6%)	2	3/183 (1.6%)	3	2/58 (3.4%)	2
Urinary tract infection	0/60 (0%)	0	7/122 (5.7%)	7	6/183 (3.3%)	7	1/58 (1.7%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/60 (1.7%)	1	1/122 (0.8%)	1	3/183 (1.6%)	3	3/58 (5.2%)	3
Vascular disorders
Hypertension	4/60 (6.7%)	4	13/122 (10.7%)	15	17/183 (9.3%)	18	8/58 (13.8%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.