A Dose Ranging Study of OPT-302 With Aflibercept for Persistent Diabetic Macular Edema

Study Overview
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Brief Summary
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A two part, multi-center study consisting of a Phase 1b open label, sequential dose escalation followed by a Phase 2a randomized, double-masked, dose expansion evaluating OPT-302 in combination with aflibercept in participants with persistent central-involved Diabetic Macular Edema.

Official Title
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Phase 1b/2a Study of OPT-302 in Combination With Aflibercept for Persistent Central-involved Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Biological: Aflibercept
* Biological: OPT-302
* Other: Sham intravitreal injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of diabetic macular edema (DME) ≤ 2 year Persistent DME despite prior intravitreal anti-VEGF-A therapy with a sub-optimal response Three or more prior anti-VEGF-A therapy intravitreal injections EDTRS BCVA score ≤ 73 and ≥ 24 letters Exclusion Criteria: Ocular disorders or ocular treatments which may interfere with assessment of visual acuity, assessment of toxicity, or fundus photography in the Study Eye HbA1c ≥ 12% and/or recent signs of uncontrolled diabetes Any clinically significant disorder or condition or disease (e.g. cardiovascular, renal conditions) that would make the participant unsuitable for the study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 1b - sequential dose followed by Phase 2a - parallel arm
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302<br>2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 0.3 mg OPT-302 intravitreal injection (0.05 mL) | Biological: Aflibercept<br>* Intravitreal injection<br>* Other names: Eylea;Biological: OPT-302<br>* Intravitreal Injection<br>|
| Experimental: Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302<br>2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL) | Biological: Aflibercept<br>* Intravitreal injection<br>* Other names: Eylea;Biological: OPT-302<br>* Intravitreal Injection<br>|
| Experimental: Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302<br>2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL) | Biological: Aflibercept<br>* Intravitreal injection<br>* Other names: Eylea;Biological: OPT-302<br>* Intravitreal Injection<br>|
| Experimental: Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302<br>2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL) | Biological: Aflibercept<br>* Intravitreal injection<br>* Other names: Eylea;Biological: OPT-302<br>* Intravitreal Injection<br>|
| Sham Comparator: Ph 2a: 2.0 mg aflibercept with sham<br>2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection | Biological: Aflibercept<br>* Intravitreal injection<br>* Other names: Eylea;Other: Sham intravitreal injection<br>* Sham (mock) intravitreal injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Safety and Tolerability will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events and CTC v4.0 (if available, otherwise protocol defined grading were used) | Baseline to Week 12 | 
| Phase 2a: Response Rate as Defined by Proportion of Participants Receiving Combination of OPT-302 and Aflibercept Achieving at Least a 5-letter Gain in BCVA Compared to Baseline at Week 12 According to ETDRS Criteria | BCVA will be measured according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in BCVA | Mean change in Best Corrected Visual Acuity (BCVA). BCVA will be measured according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria | Baseline to Week 12 | 
| Mean Change in CST | Mean change in central subfield thickness (CST) on spectral domain coherence tomography (SD-OCT) | Baseline to Week 12 |