4D-150 in Patients With Diabetic Macular Edema

Sponsor

4D Molecular Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05930561

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema Diabetic Retinopathy	Biological: 4D-150 IVT Biological: Aflibercept IVT	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In Dose Confirmation, subjects (n=18) will be randomized to receive one of two dose levels of 4D-150 (n=6 per dose level) or aflibercept control (n=6). In Dose Expansion, 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).In Dose Confirmation, subjects (n=18) will be randomized to receive one of two dose levels of 4D-150 (n=6 per dose level) or aflibercept control (n=6). In Dose Expansion, 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).

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Participants and outcomes assessors will be masked to treatment arm for the duration of the trial.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 30, 2023

Anticipated Primary Completion Date :

Feb 29, 2028

Anticipated Study Completion Date :

Jul 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4D-150 Part 1 Dose Confirmation Dose Level 1 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day1.	Biological: 4D-150 IVT 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
Experimental: 4D-150 Part 1 Dose Confirmation Dose Level 2 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day1.	Biological: 4D-150 IVT 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
Active Comparator: 4D-150 Part 1 Dose Confirmation Control Aflibercept will be administered PRN.	Biological: Aflibercept IVT Commercially available Active Comparator Other Names: Eylea
Experimental: 4D-150 Part 2 Dose Expansion Dose Level 1 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day1.	Biological: 4D-150 IVT 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
Experimental: 4D-150 Part 2 Dose Expansion Dose Level 2 4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day1.	Biological: 4D-150 IVT 4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
Active Comparator: 4D-150 Part 2 Dose Expansion Control Aflibercept at a fixed regimen will be administered.	Biological: Aflibercept IVT Commercially available Active Comparator Other Names: Eylea

Outcome Measures

Primary Outcome Measures

Annualized number of aflibercept injections in the study eye [52 weeks]

Secondary Outcome Measures

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]

Other Outcome Measures

Incidence and severity of treatment-emergent adverse events and serious adverse events, including clinically significant changes in safety parameters [104 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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 6 months or at least 5 half-lives (whichever is longer) prior to Screening
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