Study of Intravitreal (IVT) REGN910-3 and IVT REGN910 in Patients With Either Neovascular (Wet) Age Related Macular Degeneration (AMD) or Diabetic Macular Edema (DME)

Study Overview
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Brief Summary
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The primary objective of the study is to investigate the safety and tolerability of intravitreal (IVT) REGN910-3 and IVT REGN910 in patients with neovascular age-related macular degeneration (AMD), and separately in patients with diabetic macular edema (DME).

Official Title
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An Open-Label, Dose-Escalation Study of the Safety and Tolerability of Intravitreal (IVT) REGN910-3 and IVT REGN910 in Patients With Either Neovascular AMD or DME

Conditions
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Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: For patients with AMD: Active subfoveal choroidal neovascularization (CNV) secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by FA or OCT in the study eye, as determined by the investigator Men or women ≥50 years and older For patients with DME: Patients with clinically significant DME with central involvement (≥300 μm in the central subfield on spectral domain OCT) Men or women ≥18 years and older Key Exclusion Criteria: For patients with neovascular AMD: Evidence of choroidal neovascularization (CNV) due to any cause other than AMD in either eye Evidence of diabetic retinopathy (DR) or DME in either eye For patients with DME: Evidence of neovascular AMD or CNV due to any cause in either eye Prior IAI in either eye IVT bevacizumab, ranibizumab, or pegaptanib sodium in the study eye within 8 weeks of day 1 or an AE with any of these previous treatments that would preclude administration of drug in this study Any prior treatment with angiopoietin inhibitors Any prior systemic (IV) anti-VEGF administration History of vitreoretinal surgery in the study eye Pan retinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of the screening visit Previous use of intraocular or periocular corticosteroids in the study eye within 4 months of screening (The inclusion/ exclusion criteria provided above are not intended to contain all considerations relevant to a subject's potential participation in this clinical trial).

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohorts 1 through 4<br>Participants in cohorts 1 through 4 will receive IVT REGN910-3 and IAI | Drug: REGN910-3<br> <br> Drug: Intravitreal Aflibercept Injection (IAI)<br> <br> * Other names: EYLEA®;|
| Experimental: Cohort 5<br>Participants in cohort 5 will receive IVT REGN910 and IAI | Drug: REGN910<br> <br> Drug: Intravitreal Aflibercept Injection (IAI)<br> <br> * Other names: EYLEA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of TEAEs through week 24 in patients treated with IVT REGN910-3 and IVT REGN910 TEAEs through week 24 in patients treated with IVT REGN910-3 and IVT REGN910 | Change from baseline to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile | PK profile may include, but is not limited to, the following: AUCall - area under the curve (AUC) computed from time zero to the time of the last concentration AUCall/Dose - AUCall-to-dose ratio AUClast - AUC computed from time zero to the time of the last positive concentration AUClast/Dose - AUClast-to-dose ratio Cmax - the peak concentration Cmax/Dose - Cmax-to-dose ratio | Baseline to week 24 | 
| Development of Anti-drug antibodies (ADA) after IVT injection of REGN910-3 |  | Baseline to week 24 |