NCT05930561

Brief Summary

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

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P50-P75 for phase_2

Timeline
35mo left

Started Aug 2023

Longer than P75 for phase_2

Geographic Reach
2 countries

6 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress49%
Aug 2023Feb 2029

First Submitted

Initial submission to the registry

June 26, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 5, 2023

Completed
1 month until next milestone

Study Start

First participant enrolled

August 9, 2023

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2029

Last Updated

September 22, 2025

Status Verified

September 1, 2025

Enrollment Period

5.6 years

First QC Date

June 26, 2023

Last Update Submit

September 17, 2025

Conditions

Diabetic Macular EdemaDiabetic Retinopathy

Keywords

Retinal gene therapyIntravitreal gene therapyDMESPECTRA

Outcome Measures

Primary Outcomes (2)

  • Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters (Part 1)

    60 months

  • Annualized number of aflibercept injections in the study eye (Part 2)

    52 weeks

Secondary Outcomes (3)

  • Mean cumulative number of aflibercept injections over time

    52 weeks

  • Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart at Weeks 52 and 104

    104 weeks

  • Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) at Weeks 104

    104 weeks

Other Outcomes (3)

  • Incidence and severity of treatment-emergent adverse events and serious adverse events, including clinically significant changes in safety parameters

    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

    104 weeks

  • Change in levels of aflibercept protein in aqueous humor and serum overtime

    104 weeks

Study Arms (5)

4D-150 Part 1 Dose Confirmation Dose Level 1

EXPERIMENTAL

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 Part 1 Dose Confirmation Dose Level 2

EXPERIMENTAL

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 Part 2 Dose Expansion Dose Level 1

EXPERIMENTAL

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 Part 2 Dose Expansion Dose Level 2

EXPERIMENTAL

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 Part 2 Dose Expansion Control

ACTIVE COMPARATOR

Aflibercept at a fixed regimen will be administered.

Biological: Aflibercept IVT

Interventions

4D-150 IVTBIOLOGICAL

4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.

4D-150 Part 1 Dose Confirmation Dose Level 14D-150 Part 1 Dose Confirmation Dose Level 24D-150 Part 2 Dose Expansion Dose Level 14D-150 Part 2 Dose Expansion Dose Level 2
Aflibercept IVTBIOLOGICAL

Commercially available Active Comparator

Also known as: Eylea
4D-150 Part 2 Dose Expansion Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

Location

Verum Research, LLC

Eugene, Oregon, 97401, United States

Location

Erie Retina Research

Erie, Pennsylvania, 16507, United States

Location

Austin Clinical Research

Austin, Texas, 78750, United States

Location

Piedmont Eye Center

Lynchburg, Virginia, 24502, United States

Location

Emanuelli Research and Development Center

Arecibo, X00612, Puerto Rico

Location

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal DiseasesEye DiseasesDiabetic AngiopathiesVascular DiseasesCardiovascular DiseasesDiabetes ComplicationsDiabetes MellitusEndocrine System Diseases

Study Officials

  • Julie Clark, MD

    4D Molecular Therapeutics

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
No masking in Dose Confirmation (Part 1). In Dose Expansion (Part 2), participants and outcomes assessors will be masked to the treatment arm for the duration of the trial.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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).
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 26, 2023

First Posted

July 5, 2023

Study Start

August 9, 2023

Primary Completion (Estimated)

February 28, 2029

Study Completion (Estimated)

February 28, 2029

Last Updated

September 22, 2025

Record last verified: 2025-09

Locations

PR(1)US(5)