Diabetic Macular Edema
Conditions
Brief summary
The primary objective of the study was to compare the efficacy of intravitreal (IVT)-administered REGN910-3 compared to intravitreal aflibercept injection (IAI) in improving best corrected visual acuity (BCVA) in participants with diabetic macular edema (DME).
Interventions
DRUGREGN910-3
Co-formulation for intravitreal (IVT) injection consisting of REGN910 (nesvacumab) and REGN3 (aflibercept)
Sponsors
Bayer
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus who have clinically significant DME with central involvement in the study eye 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 macular edema due to any cause other than diabetes mellitus in either eye 2. IVT anti-VEGF in the study eye within 12 weeks of the screening visit 3. Panretinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of screening Note: Other inclusion/
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 12 | Baseline, 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. |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | Baseline, Week 36 | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 36. |
Secondary
| 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 12 | Baseline, 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 LOCF post-baseline value at Week 12. |
| Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | Baseline, 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. |
| Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | Baseline, Week 12 | The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative). |
| Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | Baseline, Week 36 | The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 70 sites in US. A total of 438 participants were screened in the study.
Pre-assignment details
Out of 438 participants, 302 were randomized & treated in study. Participants were randomized in 1:2:3 to receive REGN910-3 3:2mg, REGN910-3 6:2mg & 2mg intravitreal aflibercept injection 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 milligram (mg):2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32 | 50 |
| 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. | 100 |
| Aflibercept 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 or REGN910-3 (6 mg:2 mg) at week 16 or 20 and Q8 through week 32. | 152 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Baseline (Day 1) up to Week 12 | Death | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline (Day 1) up to Week 12 | Lost to Follow-up | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Baseline (Day 1) up to Week 12 | Other Unspecified | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Baseline (Day 1) up to Week 12 | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Baseline (Day 1) up to Week 12 | Withdrawal by Subject | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| From Week 12 up to Week 36 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
| From Week 12 up to Week 36 | Death | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| From Week 12 up to Week 36 | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| From Week 12 up to Week 36 | Physician Decision | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| From Week 12 up to Week 36 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | REGN910-3 (3 mg: 2 mg) | REGN910-3 (6 mg:2 mg) | Aflibercept 2 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 9.12 | 62.5 years STANDARD_DEVIATION 10.36 | 59.5 years STANDARD_DEVIATION 10.2 | 61.0 years STANDARD_DEVIATION 10.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 21 Participants | 26 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 78 Participants | 125 Participants | 247 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 8 Participants | 19 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) White | 37 Participants | 87 Participants | 121 Participants | 245 Participants |
| Sex: Female, Male Female | 21 Participants | 49 Participants | 68 Participants | 138 Participants |
| Sex: Female, Male Male | 29 Participants | 51 Participants | 84 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 50 | 0 / 100 | 4 / 152 |
| other Total, other adverse events | 18 / 50 | 42 / 100 | 55 / 152 |
| serious Total, serious adverse events | 6 / 50 | 18 / 100 | 31 / 152 |
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: Baseline, 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 | 6.8 Letters correctly read | Standard Deviation 7.3 |
| 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 | 8.5 Letters correctly read | Standard Deviation 6.89 |
| Aflibercept 2 mg | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12 | 8.8 Letters correctly read | Standard Deviation 9.71 |
p-value: 0.1368ANCOVA
Comparison: Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.p-value: 0.9716ANCOVA
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: Baseline, Week 36
Population: FAS secondary randomization set = all participants in full analysis set (FAS) who had completed study through week 12, received any study drug after secondary randomization or after Week 12, had BCVA assessment at Week 12 \& had at least 1 post-Week 16 BCVA assessment. Overall Number of Participants Analyzed=Participants evaluable for this endpoint.
| 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 | 9.8 Letters correctly read | Standard Deviation 9.92 |
| 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 | 10.3 Letters correctly read | Standard Deviation 8.2 |
| Aflibercept 2 mg | Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36 | 8.5 Letters correctly read | Standard Deviation 7.74 |
| Aflibercept 2 mg Q4 to Aflibercept 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 | 8.7 Letters correctly read | Standard Deviation 10.65 |
| Aflibercept 2 mg Q4 to Aflibercept 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 | 10.0 Letters correctly read | Standard Deviation 10.37 |
| Aflibercept 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 | 11.9 Letters correctly read | Standard Deviation 12.01 |
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: 0.166595% CI: [-0.9, 5.2]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: 0.222395% CI: [-1.16, 4.95]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: 0.794395% CI: [-2.54, 3.32]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: 0.665595% CI: [-2.35, 3.67]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: 0.127895% CI: [-0.67, 5.33]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: 0.3159-1.51% CI: [-4.47, 1.45]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: 0.853795% CI: [-3.18, 2.63]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 LOCF post-baseline value at Week 12.
Time frame: Baseline, 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 | -169.4 Microns | Standard Deviation 155.86 |
| 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 | -184.0 Microns | Standard Deviation 143.69 |
| Aflibercept 2 mg | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12 | -174.6 Microns | Standard Deviation 160.36 |
Comparison: Analysis was performed using analysis of covariance (ANCOVA) model with baseline measurement as a covariate and treatment group as fixed factors.p-value: 0.110595% CI: [-54.46, 5.61]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: 0.0183ANCOVA
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: Baseline, 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 | -210.4 Microns | Standard Deviation 164.06 |
| 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 | -223.4 Microns | Standard Deviation 145.35 |
| Aflibercept 2 mg | Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36 | -193.7 Microns | Standard Deviation 158.29 |
| Aflibercept 2 mg Q4 to Aflibercept 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 | -161.9 Microns | Standard Deviation 125.99 |
| Aflibercept 2 mg Q4 to Aflibercept 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 | -210.6 Microns | Standard Deviation 202.15 |
| Aflibercept 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 | -203.7 Microns | Standard Deviation 163.08 |
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: 0.004ANCOVA
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: 0.036595% CI: [-78.46, -2.57]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: 0.045495% CI: [-73.53, -0.77]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: 0.926695% CI: [-35.54, 39.03]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: 0.411695% CI: [-52.58, 21.59]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: 0.857495% CI: [-33.42, 40.14]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: 0.035195% CI: [-75.06, -2.73]ANCOVA
Secondary
Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative).
Time frame: Baseline, 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) | Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 13.3 Percentage of participants |
| REGN910-3 (6 mg:2 mg) | Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 21.3 Percentage of participants |
| Aflibercept 2 mg | Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 15.2 Percentage of participants |
Comparison: Analysis was performed using analysis of Cochran-Mantel-Haenszel model.p-value: 0.761795% CI: [-13.5, 9.8]Cochran-Mantel-Haenszel
Comparison: Analysis was performed using analysis of Cochran-Mantel-Haenszel model.p-value: 0.2268Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative).
Time frame: Baseline, Week 36
Population: FAS secondary randomization set was used. Overall Number of Participants Analyzed = Participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| REGN910-3 (3 mg: 2 mg) | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 26.7 Percentage of participants |
| REGN910-3 (6 mg:2 mg) | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 34.1 Percentage of participants |
| Aflibercept 2 mg | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 34.0 Percentage of participants |
| Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8 | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 26.1 Percentage of participants |
| Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12 | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 25.5 Percentage of participants |
| Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8 | Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline | 35.4 Percentage of participants |
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.889695% CI: [-20.4, 17.7]Cochran-Mantel-Haenszel
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.502195% CI: [-12.6, 25.5]Cochran-Mantel-Haenszel
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.527395% CI: [-12.8, 24.7]Cochran-Mantel-Haenszel
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.868395% CI: [-19.7, 16.6]Cochran-Mantel-Haenszel
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.354695% CI: [-9.8, 27.4]Cochran-Mantel-Haenszel
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.980195% CI: [-19, 19.5]Cochran-Mantel-Haenszel
Comparison: Difference with Confidence Interval was calculated using Mantel-Haenszel weighting scheme adjusted by BCVA stratification variable.p-value: 0.352895% CI: [-9.9, 27.4]Cochran-Mantel-Haenszel