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

Phase 1

Completed

• Conditions: Diabetic Macular Edema
• Interventions: Biological: Aflibercept; Biological: OPT-302; Other: Sham intravitreal injection

• Registration Number: NCT03397264
• Lead Sponsor: Opthea Limited

Brief Summary

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.

Detailed Description

Study OPT-302-1003 was designed as a 2-part, multicenter study consisting of a Phase 1b open-label, sequential dose escalation followed by a Phase 2a randomized, parallel-group, sham-controlled, double-masked, dose-expansion evaluating intravitreal OPT-302 in combination with aflibercept in participants with persistent central-involved diabetic macula edema.

Study Timeline

• Study First Submitted: 2018-01-01
• Study First Submitted QC: 2018-01-05
• Study First Posted: 2018-01-11
• Study Start: 2018-01-16
• Primary Completion: 2020-03-26
• Study Completion: 2020-06-11
• Results First Submitted: 2022-03-21
• Results First Submitted QC: 2022-05-30
• Results First Posted: 2022-06-22
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 153

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302	Aflibercept	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 0.3 mg OPT-302 intravitreal injection (0.05 mL)
Ph 1b: 2.0 mg aflibercept with 0.3 mg OPT-302	OPT-302	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 0.3 mg OPT-302 intravitreal injection (0.05 mL)
Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302	OPT-302	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302	OPT-302	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 1b: 2.0 mg aflibercept with 1.0 mg OPT-302	Aflibercept	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 1.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 2a: 2.0 mg aflibercept with sham	Sham intravitreal injection	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection
Ph 1b: 2.0 mg aflibercept with 2.0 mg OPT-302	Aflibercept	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302	Aflibercept	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 2a: 2.0 mg aflibercept with 2.0 mg OPT-302	OPT-302	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by 2.0 mg OPT-302 intravitreal injection (0.05 mL)
Ph 2a: 2.0 mg aflibercept with sham	Aflibercept	2.0 mg aflibercept intravitreal injection (0.05 mL) followed by sham intravitreal injection

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Baseline to Week 12	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)
Phase 2a: Response Rate Defined as Proportion of Participants Receiving OPT-302 With Aflibercept Achieving at Least a 5-letter Gain in BCVA at Week 12	Baseline to Week 12	Change from baseline in Best Corrected Visual Acuity (BCVA) will be measured at Week 12 according to Early Treatment Diabetic Retinopathy Score (ETDRS) criteria

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Opthea Investigational Site; 🇱🇻 Riga, Latvia