Study of Intravitreal REGN2176-3 in Participants With Neovascular (Wet) Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The primary objective of the study was to explore the effect of REGN2176-3 on the Early Treatment Diabetic Retinopathy Scale (ETDRS) best-corrected visual acuity (BCVA) in participants with neovascular age-related macular degeneration (AMD), compared to intravitreal aflibercept injection (IAI) monotherapy. The secondary objectives of the study were the following: To explore the effect of 2 dose levels of IVT REGN2176-3 on anatomical changes of CNV in participants with nAMD compared to IAI monotherapy (at week 12) To evaluate if short-term treatment with REGN2176-3 followed by IAI monotherapy offered the same or additional benefit compared to continuous treatment with REGN2176-3. Also to determine if there was benefit in initiating IAI treatment prior to REGN2176-3 compared to continuous treatment with IAI. To assess the safety and tolerability of IVT REGN2176-3 in participants with nAMD

Official Title
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A Phase 2, Double-Masked, Randomized, Controlled, Multiple-Dose, Regimen-Ranging Study of the Efficacy and Safety of Intravitreal REGN2176-3 in Patients With Neovascular Age-Related Macular Degeneration

Conditions
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Neovascular Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: REGN2176-3
* Drug: Intravitreal Aflibercept Injection (IAI)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Men or women ≥50 years of age Active subfoveal CNV secondary to AMD as evidenced by FA in the study eye, as determined by the reading center, including juxtafoveal lesions that affect the fovea BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye at the screening visit Provide signed informed consent Key Exclusion Criteria: Any prior treatment with anti-VEGF treatment in the study eye Any prior treatment (ie, systemic or ocular treatment) with PDGF or PDGFR inhibitors Dense fibrotic scar or atrophy in the study eye involving the center of the fovea Presence of retinal pigment epithelial tears or rips involving the macula in the study eye Prior vitrectomy in the study eye Any history of macular hole of stage 2 and above in the study eye Any intraocular or periocular surgery within 3 months of day 1 in the study eye, except lid surgery History of corneal transplant in the study eye Evidence of diabetic retinopathy or diabetic macular edema in either eye Positive serum human chorionic gonadotropin/urine pregnancy test at the screening or baseline visit

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN2176-3 (1 mg: 2 mg)<br>Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52. | Drug: REGN2176-3<br> <br> |
| Experimental: REGN2176-3 (3 mg: 2 mg)<br>Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52. | Drug: REGN2176-3<br> <br> |
| Experimental: Intravitreal Aflibercept Injection (IAI) 2 mg<br>IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52. | Drug: Intravitreal Aflibercept Injection (IAI)<br> <br> * Other names: Eylea®;|
| Experimental: REGN2176-3 (3 mg: 2 mg) to IAI 2 mg<br>Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly with IAI 2 mg up to Week 28, then criteria based re-dosing from Week 28-52. | Drug: Intravitreal Aflibercept Injection (IAI)<br> <br> * Other names: Eylea®;|
| Experimental: IAI 2 mg to REGN2176-3 (3 mg:2 mg)<br>IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly with REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) up to Week 28, then criteria based re-dosing from Week 28-52. | Drug: REGN2176-3<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye at Week 12 | 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 12. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 12, as Measured by Optical Coherence Tomography (OCT) | 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. | Baseline, Week 12 | 
| Percentage of Participants With Complete Resolution of Intraretinal and Subretinal Fluid From Baseline at Week 12 Measured by Optical Coherence Tomography (OCT) | 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. | Week 12 | 
| Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 Measured by Fluorescein Angiography (FA) | The anatomical state of the retinal vasculature of the study eye and the fellow eye was evaluated by funduscopic examination, fundus photography and FA to evaluate the total lesion area, CNV area, classic CNV area, and fluorescein leakage. CNV area values measured in square millimeters, each disc area was equivalent to 2.54 mm^2 on the retina; lower values represent better outcomes. | Baseline, Week 12 | 
| Change From Baseline in Total Lesion Size at Week 12 Measured by Fluorescein Angiography (FA) | Total Lesion Size was assessed by Fluorescein Angiography. | Baseline, Week 12 | 
| Percentage of Participants Who Gained At Least 15 Letters in BCVA From Baseline at Week 12, Measured by 4-meter Early Treatment Diabetic Retinopathy Scale (ETDRS) | 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. This outcome assessed the percentage of participants who gained 15 or more letters of visual acuity at Week 12 compared with baseline. | Week 12 | 
| Percent Change From Baseline in Subretinal Hyperreflectivity Material (SHM) at Week 12 Measured by Optical Coherence Tomography (OCT) | SHM 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. | Baseline, Week 12 | 
| Change From Baseline in Central Retinal/Lesion Thickness at Week 12 Measured by Optical Coherence Tomography (OCT) | 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. | Baseline, Week 12 |