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

Study Overview
=================
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).

Official Title
-----------------
A Randomized, Double-Masked, Active-Controlled Phase 2 Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal REGN910-3 in Patients With Neovascular Age-Related Macular Degeneration

Conditions
-----------------
Neovascular Age-Related Macular Degeneration

Intervention / Treatment
-----------------
* Drug: REGN910-3
* Drug: Intravitreal Aflibercept Injection (IAI)


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: 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 BCVA ETDRS letter score of 73 to 24 (Snellen equivalent of 20/40 to 20/320) in the study eye. Willing and able to comply with clinic visits and study-related procedures. Provide signed informed consent. Key Exclusion Criteria: Evidence of CNV due to any cause other than AMD in either eye Prior IVT anti-VEGF in the study eye Evidence of DME or diabetic retinopathy (defined as more than 1 microaneurysm) in either eye in diabetic patients Any history of macular hole of stage 2 and above in the study eye

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN910-3 (3 mg: 2 mg)<br>Participants were administered intravitreal injection of REGN910-3 (3 milligram [mg]:2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32. | Drug: REGN910-3<br> <br> |
| Experimental: REGN910-3 (6 mg:2 mg)<br>Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) Q8 or Q12 (beginning at Week 16 or Week 20) through Week 32. | Drug: REGN910-3<br> <br> |
| Experimental: Aflibercept (IAI) 2 mg<br>Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI Q8 or Q12 (beginning at Week 16 or 20) or REGN910-3 (6 mg:2 mg) Q8 beginning at Week 16 through Week 32. | Drug: REGN910-3<br> <br> Drug: Intravitreal Aflibercept Injection (IAI)<br> <br> * Other names: BAY86-5321;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 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. | At Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 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. | At Week 36 | 
| 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. | At Week 12 | 
| 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. | At Week 36 | 
| 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. | At Week 12 | 
| 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. | At Week 36 |