4D-150 in Patients With Diabetic Macular Edema

Study Overview
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Brief Summary
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Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME).

Detailed Description
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This Phase 2 trial is a prospective, multicenter, randomized, active-controlled, double-masked dose-ranging trial to evaluate the safety and efficacy of 4D-150 in adults with DME. The trial will be conducted in two parts: Dose Confirmation and Dose Expansion.

Official Title
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A Phase 2 Randomized, Active-Controlled, Double-masked Trial of Intravitreal 4D-150 Gene Therapy in Adults With Diabetic Macular Edema (SPECTRA)

Conditions
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Diabetic Macular Edema, Diabetic Retinopathy

Intervention / Treatment
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* Biological: 4D-150 IVT
* Biological: Aflibercept IVT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age Type I or Type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea; diagnosis of DME must be within 2 years of Screening Demonstrate clinical response to on-study aflibercept injection in the study eye. Decreased visual acuity attributable primarily to DME BCVA in the study eye between 25 and 83 ETDRS letters, inclusive ( 20/320 and 20/25, respectively) at Screening Study eye amenable to IVT injection Sufficient clear ocular media, pupil dilation and fixation in the study eye to permit adequate imaging; ability to perform tests of visual and retinal function and structure; and ability to comply with other protocol-specified procedures Provide written informed consent Exclusion Criteria: Macular edema in the study eye considered to be secondary to a cause other than DME Systemic anti-VEGF treatment (e.g. sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 3 months (or at least 5 half-lives, whichever is longer) prior to 4D-150 administration (Day 1) Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye Any concurrent ocular condition in the study eye that is likely to require surgical intervention (e.g. cataract surgery) during the 2 year (104 week) study duration Note: Other inclusion/exclusion criteria apply.

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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In Dose Confirmation (Part 1), subjects (n=12-18) will be sequentially assigned to one of two open-label dose levels of 4D-150 (n=6-9 per dose level). In Dose Expansion (Part 2), subjects (n=54) will be randomized to receive one of two dose levels of 4D-150 (n=18 per dose level) based on results from Dose Confirmation, or aflibercept control (n=18). Subjects will be masked to treatment arm in Dose Expansion (Part 2).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4D-150 Part 1 Dose Confirmation Dose Level 1<br>4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. | Biological: 4D-150 IVT<br>* 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.<br>|
| Experimental: 4D-150 Part 1 Dose Confirmation Dose Level 2<br>4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. | Biological: 4D-150 IVT<br>* 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.<br>|
| Experimental: 4D-150 Part 2 Dose Expansion Dose Level 1<br>4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. | Biological: 4D-150 IVT<br>* 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.<br>|
| Experimental: 4D-150 Part 2 Dose Expansion Dose Level 2<br>4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1. | Biological: 4D-150 IVT<br>* 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.<br>|
| Active Comparator: 4D-150 Part 2 Dose Expansion Control<br>Aflibercept at a fixed regimen will be administered. | Biological: Aflibercept IVT<br>* Commercially available Active Comparator<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized number of aflibercept injections in the study eye |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean cumulative number of aflibercept injections over time |  | 52 weeks | 
| Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart |  | 104 weeks | 
| Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) |  | 104 weeks | 
| Percentage of subjects with a ≥2 and ≥3-Step Diabetic Retinopathy Severity (DRS) improvement from baseline on the ETDRS-DRSS |  | 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinal gene therapy, Intravitreal gene therapy, DME, SPECTRA