4D-150 in Patients With Diabetic Macular Edema

September 17, 2025 updated by: 4D Molecular Therapeutics

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

72

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Arecibo, Puerto Rico, X00612
        • Emanuelli Research and Development Center
  • United States
    • Maryland
      • Hagerstown, Maryland, United States, 21740
        • Cumberland Valley Retina Consultants
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Verum Research, LLC
    • Pennsylvania
      • Erie, Pennsylvania, United States, 16507
        • Erie Retina Research
    • Texas
      • Austin, Texas, United States, 78750
        • Austin Clinical Research
    • Virginia
      • Lynchburg, Virginia, United States, 24502
        • Piedmont Eye Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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
  • CST ≥ 350 μm (Spectralis SD-OCT) in the study eye at Screening, confirmed by the independent reading center
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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 Day 1.
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 Day 1.
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 1
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
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 Day 1.
Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters (Part 1)
Time Frame: 60 months
60 months
Annualized number of aflibercept injections in the study eye (Part 2)
Time Frame: 52 weeks
52 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Mean cumulative number of aflibercept injections over time
Time Frame: 52 weeks
52 weeks
Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart at Weeks 52 and 104
Time Frame: 104 weeks
104 weeks
Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) at Weeks 104
Time Frame: 104 weeks
104 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of treatment-emergent adverse events and serious adverse events, including clinically significant changes in safety parameters
Time Frame: 104 weeks
104 weeks
Development of anti-drug antibodies to capsid protein (4D-R100) and the transgene product (aflibercept) and change in antibody titers in subjects receiving 4D-150
Time Frame: 104 weeks
104 weeks
Change in levels of aflibercept protein in aqueous humor and serum overtime
Time Frame: 104 weeks
104 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

4D Molecular Therapeutics

Investigators

  • Study Director: Julie Clark, MD, 4D Molecular Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 9, 2023

Primary Completion (Estimated)

February 28, 2029

Study Completion (Estimated)

February 28, 2029

Study Registration Dates

First Submitted

June 26, 2023

First Submitted That Met QC Criteria

June 26, 2023

First Posted (Actual)

July 5, 2023

Study Record Updates

Last Update Posted (Actual)

September 22, 2025

Last Update Submitted That Met QC Criteria

September 17, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4D-150-C002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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