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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
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
Hide 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
Arm/Group Title REGN910-3 (3 mg:2 mg) REGN910-3 (6 mg:2 mg) Aflibercept (IAI) 2 mg Total
Hide 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
Hide 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
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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]
Show Statistical Analysis 3 Hide 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]
Show Statistical Analysis 4 Hide 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]
Show Statistical Analysis 5 Hide 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]
Show Statistical Analysis 6 Hide 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]
Show Statistical Analysis 7 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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]
Show Statistical Analysis 3 Hide 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]
Show Statistical Analysis 4 Hide 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]
Show Statistical Analysis 5 Hide 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]
Show Statistical Analysis 6 Hide 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]
Show Statistical Analysis 7 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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]
Show Statistical Analysis 3 Hide 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]
Show Statistical Analysis 4 Hide 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]
Show Statistical Analysis 5 Hide 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]
Show Statistical Analysis 6 Hide 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]
Show Statistical Analysis 7 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Show Statistical Analysis 1 Hide 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]
Show Statistical Analysis 2 Hide 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]
Show Statistical Analysis 3 Hide 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]
Show Statistical Analysis 4 Hide 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]
Show Statistical Analysis 5 Hide 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]
Show Statistical Analysis 6 Hide 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]
Show Statistical Analysis 7 Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
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
Hide 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%)    
Show Serious Adverse Events Hide 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
Show Other (Not Including Serious) Adverse Events Hide 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
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
Name/Title: Clinical Trial Management
Organization: Regeneron Pharmaceuticals
Phone: 844-734-6643
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02713204     History of Changes
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