Neovascular Age-Related Macular Degeneration
Conditions
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).
Interventions
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 87 sites in the United States. A total of 560 participants were screened in the study.
Pre-assignment details
Out of 560 participants, 365 were randomized & treated. Participants were randomized in 1:2:3 to receive REGN910-3 3:2mg, REGN910-3 6:2mg & 2mg intravitreal aflibercept injection (IAI) followed by re-randomization at week 12 in REGN910-3 6:2mg & IAI 2mg arm. Not all participants who completed Week 12 were re-randomized & continued to Week 36.
Participants by arm
| Arm | Count |
|---|---|
| REGN910-3 (3 mg:2 mg) 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. | 59 |
| 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) at Week 16 or Week 20 and Q8 or Q12 through Week 32. | 122 |
| 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. | 183 |
| Total | 364 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Baseline (Day 1) up to Week 12 | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline (Day 1) up to Week 12 | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline (Day 1) up to Week 12 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| From Week 12 up to Week 36 | Adverse Event | 1 | 0 | 0 | 1 | 1 | 0 | 2 | 1 |
| From Week 12 up to Week 36 | Death | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 3 |
| From Week 12 up to Week 36 | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| From Week 12 up to Week 36 | Participant Re-located | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | REGN910-3 (3 mg:2 mg) | REGN910-3 (6 mg:2 mg) | Aflibercept (IAI) 2 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 79.2 years STANDARD_DEVIATION 9.37 | 79.4 years STANDARD_DEVIATION 8.91 | 78.4 years STANDARD_DEVIATION 8.37 | 78.9 years STANDARD_DEVIATION 8.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 115 Participants | 174 Participants | 346 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 58 Participants | 116 Participants | 178 Participants | 352 Participants |
| Sex: Female, Male Female | 41 Participants | 75 Participants | 110 Participants | 226 Participants |
| Sex: Female, Male Male | 18 Participants | 47 Participants | 73 Participants | 138 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 60 | 2 / 122 | 7 / 183 | 3 / 58 |
| other Total, other adverse events | 17 / 60 | 41 / 122 | 51 / 183 | 20 / 58 |
| serious Total, serious adverse events | 11 / 60 | 20 / 122 | 30 / 183 | 8 / 58 |
Outcome results
Primary
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score 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.
Time frame: At Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 | 5.2 Letters correctly read | Standard Deviation 10.51 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 | 5.6 Letters correctly read | Standard Deviation 10.59 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 | 5.4 Letters correctly read | Standard Deviation 9.85 |
p-value: 0.989495% CI: [-2.99, 3.03]ANCOVA
Comparison: Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.p-value: 0.834695% CI: [-2.09, 2.59]ANCOVA
Primary
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score 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.
Time frame: At Week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 5.9 Letters correctly read | Standard Deviation 11.95 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 6.0 Letters correctly read | Standard Deviation 12 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 6.4 Letters correctly read | Standard Deviation 12.24 |
| Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8 | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 6.9 Letters correctly read | Standard Deviation 12.49 |
| Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12 | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 4.2 Letters correctly read | Standard Deviation 12.5 |
| Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 2.9 Letters correctly read | Standard Deviation 12.16 |
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.461195% CI: [-4.41, 2]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.222595% CI: [-5.22, 1.22]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.606395% CI: [-3.97, 2.32]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.042695% CI: [-6.39, -0.11]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.007395% CI: [-7.58, -1.19]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.46995% CI: [-2.01, 4.36]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.126795% CI: [-0.69, 5.54]ANCOVA
Secondary
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) 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.
Time frame: At Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 | -182.2 Microns | Standard Deviation 172.73 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 | -200.0 Microns | Standard Deviation 152.82 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 | -178.6 Microns | Standard Deviation 138.85 |
Comparison: Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.p-value: 0.41395% CI: [-39.5, 16.2]ANCOVA
Comparison: Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.p-value: 0.658795% CI: [-26.2, 16.85]ANCOVA
Secondary
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) 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.
Time frame: At Week 36
Population: FAS secondary randomization set was used. Here Overall Number of Participants Analyzed= Participants who were evaluable for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -174.6 Microns | Standard Deviation 165.22 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -216.6 Microns | Standard Deviation 187.4 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -181.3 Microns | Standard Deviation 148.71 |
| Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8 | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -198.4 Microns | Standard Deviation 155.72 |
| Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12 | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -169.7 Microns | Standard Deviation 129.74 |
| Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -187.3 Microns | Standard Deviation 161.72 |
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.383395% CI: [-21.35, 55.43]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.514195% CI: [-25.84, 51.53]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.078595% CI: [-3.89, 71.67]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.028195% CI: [4.56, 79.98]ANCOVA
p-value: 0.393495% CI: [-21.67, 54.96]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.27995% CI: [-17.13, 59.22]ANCOVA
Comparison: Analysis was performed using ANCOVA model with baseline measurement as a covariate, and treatment group and BCVA stratification variable as fixed factors.p-value: 0.658695% CI: [-45.64, 28.88]ANCOVA
Secondary
Change From Baseline in Choroidal Neovascularization (CNV) Area 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.
Time frame: At Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 | -2.2 mm^2 | Standard Deviation 5.59 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 | -3.5 mm^2 | Standard Deviation 5.34 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 | -3.7 mm^2 | Standard Deviation 6.22 |
p-value: 0.488995% CI: [-1.01, 2.1]ANCOVA
p-value: 0.702795% CI: [-0.99, 1.46]ANCOVA
Secondary
Change From Baseline in Choroidal Neovascularization (CNV) Area 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.
Time frame: At Week 36
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 | -3.7 mm^2 | Standard Deviation 5.04 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 | -4.1 mm^2 | Standard Deviation 6.09 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 | -4.9 mm^2 | Standard Deviation 5.58 |
| Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8 | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 | -4.3 mm^2 | Standard Deviation 6.55 |
| Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12 | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 | -5.1 mm^2 | Standard Deviation 5.6 |
| Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 36 | -5.3 mm^2 | Standard Deviation 5.19 |
p-value: 0.492795% CI: [-2.34, 1.13]ANCOVA
p-value: 0.664595% CI: [-1.36, 2.13]ANCOVA
p-value: 0.309195% CI: [-2.61, 0.83]ANCOVA
p-value: 0.489895% CI: [-2.29, 1.1]ANCOVA
p-value: 0.350495% CI: [-2.5, 0.89]ANCOVA
p-value: 0.263295% CI: [-2.7, 0.74]ANCOVA
p-value: 0.805695% CI: [-1.46, 1.88]ANCOVA
Secondary
Change From Baseline in Total Lesion Area 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.
Time frame: At Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Total Lesion Area at Week 12 | -2.0 mm^2 | Standard Deviation 6.1 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Total Lesion Area at Week 12 | -3.5 mm^2 | Standard Deviation 5.45 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Total Lesion Area at Week 12 | -3.4 mm^2 | Standard Deviation 6.48 |
p-value: 0.506595% CI: [-1.11, 2.25]ANCOVA
p-value: 0.741895% CI: [-1.55, 1.1]ANCOVA
Secondary
Change From Baseline in Total Lesion Area 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.
Time frame: At Week 36
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Change From Baseline in Total Lesion Area at Week 36 | -3.0 mm^2 | Standard Deviation 5.91 |
| REGN910-3 (6 mg:2 mg) | Change From Baseline in Total Lesion Area at Week 36 | -3.9 mm^2 | Standard Deviation 5.79 |
| Aflibercept (IAI) 2 mg | Change From Baseline in Total Lesion Area at Week 36 | -4.7 mm^2 | Standard Deviation 5.35 |
| Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8 | Change From Baseline in Total Lesion Area at Week 36 | -3.9 mm^2 | Standard Deviation 6.67 |
| Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12 | Change From Baseline in Total Lesion Area at Week 36 | -4.7 mm^2 | Standard Deviation 5.43 |
| Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Change From Baseline in Total Lesion Area at Week 36 | -5.3 mm^2 | Standard Deviation 5.2 |
p-value: 0.838395% CI: [-1.99, 1.62]ANCOVA
p-value: 0.91895% CI: [-1.91, 1.72]ANCOVA
p-value: 0.123895% CI: [-3.2, 0.39]ANCOVA
p-value: 0.281995% CI: [-2.73, 0.8]ANCOVA
p-value: 0.258195% CI: [-2.78, 0.75]ANCOVA
p-value: 0.33995% CI: [-2.66, 0.92]ANCOVA
p-value: 0.955895% CI: [-1.69, 1.79]ANCOVA
Other Pre-specified
Proportion of Participants With No Retinal and/or Subretinal Fluid 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.
Time frame: At Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| REGN910-3 (3 mg:2 mg) | Proportion of Participants With No Retinal and/or Subretinal Fluid at Week 12 | 0.49 Proportion of participants |
| REGN910-3 (6 mg:2 mg) | Proportion of Participants With No Retinal and/or Subretinal Fluid at Week 12 | 0.51 Proportion of participants |
| Aflibercept (IAI) 2 mg | Proportion of Participants With No Retinal and/or Subretinal Fluid at Week 12 | 0.44 Proportion of participants |
Other Pre-specified
Proportion of Participants With No Retinal and/or Subretinal Fluid From 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.
Time frame: Baseline through Week 36
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| REGN910-3 (3 mg:2 mg) | Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 | 0.54 Proportion of participants |
| REGN910-3 (6 mg:2 mg) | Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 | 0.49 Proportion of participants |
| Aflibercept (IAI) 2 mg | Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 | 0.53 Proportion of participants |
| Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8 | Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 | 0.42 Proportion of participants |
| Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12 | Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 | 0.53 Proportion of participants |
| Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Proportion of Participants With No Retinal and/or Subretinal Fluid From Baseline Through Week 36 | 0.47 Proportion of participants |
Other Pre-specified
Time to No Retinal and/or Subretinal Fluid 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.
Time frame: Baseline through Week 36
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REGN910-3 (3 mg:2 mg) | Time to No Retinal and/or Subretinal Fluid Through Week 36 | 105.6 Days | Standard Error 11.06 |
| REGN910-3 (6 mg:2 mg) | Time to No Retinal and/or Subretinal Fluid Through Week 36 | 80.9 Days | Standard Error 9.02 |
| Aflibercept (IAI) 2 mg | Time to No Retinal and/or Subretinal Fluid Through Week 36 | 84.9 Days | Standard Error 8.01 |
| Aflibercept 2(IAI) mg Q4 to Aflibercept (IAI) 2 mg Q8 | Time to No Retinal and/or Subretinal Fluid Through Week 36 | 106.4 Days | Standard Error 11.04 |
| Aflibercept (IAI) 2 mg Q4 to Aflibercept (IAI) 2 mg Q12 | Time to No Retinal and/or Subretinal Fluid Through Week 36 | 96.5 Days | Standard Error 11.27 |
| Aflibercept (IAI) 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Time to No Retinal and/or Subretinal Fluid Through Week 36 | 107.1 Days | Standard Error 10.05 |