4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration

February 10, 2026 updated by: 4D Molecular Therapeutics

A Phase 1/2 Dose-Escalation and Randomized, Controlled, Masked Expansion Trial of Intravitreal 4D-150 Gene Therapy in Adults With Neovascular (Wet) Age-Related Macular Degeneration

Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment.

Substudies will evaluate the safety and tolerability of 4D-150 contralateral eye dosing and characterize vector shedding.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This Phase 1/2 trial is a prospective, multicenter, Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment who have demonstrated a clinical response consistent with anti-VEGF activity. The trial consists of Dose Escalation, Dose Expansion, Steroid Optimization, and[DD1.1][JA1.2] Population Extension Cohorts.

After receiving one time administration of 4D-150 by intravitreal injection (IVT), subjects will undergo assessments at monthly intervals for 24 months to assess safety and efficacy outcomes. Only subjects that received 4D-150 will then enter a long-term follow-up (LTFU) period to assess long-term safety of 4D-150 gene therapy and duration of clinical activity through year 5 (60 months).

Eligible subjects who received 4D-150 in the study eye may participate in a sub-study to evaluate one-time IVT administration of 4D-150 to the contralateral ("fellow") eye.

Additional subjects will be enrolled in a separate sub-study to characterize the vector shedding profile of one-time administration of IVT 4D-150.

In both sub-studies, subjects will undergo regular assessments to assess safety and tolerability through Week 52 and then will enter long-term follow-up for safety evaluation through year 5 (60 months).

Study Type

Interventional

Enrollment (Estimated)

215

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Contact

Study Locations

  • Puerto Rico
    • Puerto Rico
      • Arecibo, Puerto Rico, Puerto Rico, 00612
        • Recruiting
        • Emanuelli Research and Development Center, LLC
        • Principal Investigator:
          • Andres Emanuelli, MD
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Barnet Delaney Perkins Eye Center
        • Principal Investigator:
          • Suhail Alam, M.D.
        • Contact:
    • California
      • Oxnard, California, United States, 93036
      • Sacramento, California, United States, 95841
        • Recruiting
        • Retinal Consultants Medical Group
        • Principal Investigator:
          • Joel Pearlman, M.D., Ph.D.
        • Contact:
    • Colorado
      • Lakewood, Colorado, United States, 80288
        • Recruiting
        • Colorado Retina Associates
        • Principal Investigator:
          • Murtaza Adam, MD
        • Contact:
    • Florida
      • Deerfield Beach, Florida, United States, 33064
        • Suspended
        • Rand Eye Institute
      • Fort Lauderdale, Florida, United States, 33308
        • Active, not recruiting
        • Retina Vitreous Consultants, LLP DBA Retina Group of Florida
      • Gainesville, Florida, United States, 32607
        • Recruiting
        • Vitreo Retinal Associates
        • Contact:
        • Principal Investigator:
          • Christine Kay, M.D.
      • Melbourne, Florida, United States, 32901
      • Pensacola, Florida, United States, 32503
        • Recruiting
        • Retinal Specialty Institute
        • Contact:
        • Principal Investigator:
          • Sunil Gupta, M.D.
      • Tampa, Florida, United States, 33607
        • Recruiting
        • Retina Vitreous Associates of Florida
        • Principal Investigator:
          • David Eichenbaum, M.D.
        • Contact:
    • Illinois
      • Oak Forest, Illinois, United States, 60452
        • Recruiting
        • University Retina and Macula Associates
        • Principal Investigator:
          • Veeral Sheth, M.D.
        • Contact:
    • Indiana
      • Carmel, Indiana, United States, 46290
        • Recruiting
        • Retina Partners Midwest
        • Contact:
        • Principal Investigator:
          • Raj Maturi, MD
    • Maryland
      • Hagerstown, Maryland, United States, 21740
        • Recruiting
        • Cumberland Valley Retina Consultants
        • Principal Investigator:
          • Allen Hu, M.D.
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Ophthalmic Consultants of Boston & Boston Eye Surgery and Laser Center
        • Principal Investigator:
          • Jeffrey Heier, MD
        • Contact:
    • Nevada
      • Reno, Nevada, United States, 89502
    • North Carolina
      • Asheville, North Carolina, United States, 28803
        • Withdrawn
        • Western Carolina Retinal Associates
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Verum Research, LLC
        • Principal Investigator:
          • Albert Edwards, MD
        • Contact:
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Recruiting
        • Palmetto Retina Center, LLC
        • Contact:
        • Principal Investigator:
          • John Wells, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Tennessee Retina
        • Principal Investigator:
          • Carl Awh, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78750
      • McAllen, Texas, United States, 78503
        • Recruiting
        • Valley Retina Institute, PA
        • Contact:
        • Principal Investigator:
          • Victor Gonzalez, M.D.
      • The Woodlands, Texas, United States, 77384
        • Withdrawn
        • Retina Consultants of Texas
    • Washington
      • Bellevue, Washington, United States, 98004
        • Withdrawn
        • Pacific Northwest Retina LLC

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

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  • 50 years of age

Individuals eligible to participate in the trial must meet the following inclusion criteria:

  1. ≥50 years of age
  2. Diagnosed with CNV secondary to AMD (confirmed by reading center)
  3. BCVA ≥34 ETDRS letters (~20/200) in the contralateral eye, and BCVA in the study eye:
  4. Central subfield thickness (CST) and/or presence of subretinal or intraretinal fluid requiring continued anti-VEGF therapy in the study eye, as assessed by SD-OCT; and confirmed by a reading center):
  5. Study eye amenable to IVT injection
  6. Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures

  7. Currently receiving anti-VEGF treatment (e.g. ranibizumab, aflibercept, faricimab or bevacizumab) in the study eye AND has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening:

    Note: Day -7 aflibercept will be administered ≥ 4 weeks from last IVT anti-VEGF

  8. Subjects receiving 4D-150 agree to use a barrier method (e.g. condom) during intercourse for 6 months after administration of 4D-150 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period
  9. Medical records available to document history of anti-VEGF therapy (dates, drugs, and dosage) for a minimum of 12 months prior to Screening
  10. Provide written informed consent.

Contralateral Eye Sub-study-Specific Criteria:

  1. Received 4D-150 in study eye-1 at least 6 months prior to Contralateral Substudy Screening Visit NOTE: Subjects who received 4D-150 in study eye-1 as part of the Shedding Substudy are also eligible to participate in the Contralateral Eye Substudy only after biological samples from all matrices were at or below the limit of quantitation for vector genomes in at least 3 consecutive measurements AND at least 6 months has passed since 4D-150 administration to study eye-1.
  2. Macular neovascularization (MNV) secondary to AMD in study eye-2 as assessed on historical images at any time by SD-OCT (required) and FA when available or fundus photography when available or at screening based on SD-OCT, FA and fundus photography (confirmed by the reading center)
  3. History of at least 1 anti-VEGF injection in study eye-2 within 6 months prior to Screening (last anti-VEGF injection must be at least 28 days prior to Screening) AND has demonstrated a clinical response consistent with anti-VEGF activity by historical OCT at any time point prior to screening with confirmed response by the reading center (Screening OCT can be confirmatory)
  4. BCVA between 25 and 83 ETDRS letters, inclusive (20/320 20/25 Snellen) in study eye-2
  5. Study eye-2 amenable to IVT injection
  6. BCVA ≥34 ETDRS letters (~20/200) in the previously treated study eye-1
  7. Ability to comply with protocol-specified procedures and visits, in the Investigator's judgment
  8. Agree to use a barrier method (e.g. condom) during intercourse for 6 months after administration of 4D-150 to study eye-2 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period
  9. Provide written informed consent.

Shedding Substudy-specific Inclusion Criteria:

  1. ≥50 years of age
  2. Diagnosed with MNV secondary to AMD as assessed on historical images at any time by spectral domain optical coherence tomography (SD-OCT) (required) and fluorescein angiography when available or fundus photography when available or at screening based on SD-OCT, FA and fundus photography (confirmed by Reading Center)
  3. Best corrected visual acuity (BCVA) between 10 and 83 ETDRS letters, inclusive (~20/640 and 20/25, respectively) in the study eye at Screening
  4. BCVA ≥34 ETDRS letters (~20/200) in the contralateral eye
  5. Currently receiving anti-VEGF treatment (e.g. ranibizumab, aflibercept, faricimab or bevacizumab) in the study eye; minimum of 1 injection within the last 6 months (last anti-VEGF injection must be at least 28 days prior to screening) AND has demonstrated a clinical response consistent with anti-VEGF activity by historical OCT at any time prior to screening with confirmed response by the reading center (Screening OCT can be confirmatory)
  6. Study eye amenable to IVT injection
  7. Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures, in the Investigator's judgment
  8. Agree to use a barrier method (e.g. condom) during intercourse for 6 months after administration of 4D-150 to prevent fluid transmission; sexually active males should not father a child or donate sperm during this period
  9. Provide written informed consent.

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: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 4D-150 Dose Escalation up to 4 dose levels
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 Dose Expansion Dose 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 Dose Expansion Dose 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
Active Comparator: 4D-150 Dose Expansion Control
Aflibercept at a fixed regimen will be administered.
Biological: Aflibercept IVT
Commercially available Active Comparator Other Name: Eylea
Experimental: 4D-150 Steroid Optimization
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 Population Extension Dose 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 Population Extension Dose 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 Population Extension Dose 3
4D-150 will be administered at the assigned dose
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 Contralateral Eye Dose
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 Vector Shedding Dose
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 treatment emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in safety parameters
Time Frame: 52 weeks
52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to receiving the first supplemental aflibercept injection
Time Frame: 52 weeks
52 weeks
Percentage of subjects requiring supplemental aflibercept injections over 52 weeks
Time Frame: 52 weeks
52 weeks
Number of supplemental aflibercept injections over 52 weeks
Time Frame: 52 weeks
52 weeks
Change from baseline in BCVA over time (up to 52 weeks) as assessed using the ETDRS Visual Acuity Chart
Time Frame: 52 weeks
52 weeks
Change from baseline in central subfield thickness (CST) over time (up to 52 weeks) measured by spectral domain optical coherence tomography (SD-OCT)
Time Frame: 52 weeks
52 weeks
Percent Change in Annualized Mean Number of anti-VEGF IVT injections before and after the 4D-150 injection
Time Frame: Before and after the 4D-150 injection (or Day 1 for the aflibercept only arm)
Percent change in annualized mean number of anti-VEGF IVT injections before and after the 4D-150 injection (or Day 1 for the aflibercept only arm)
Before and after the 4D-150 injection (or Day 1 for the aflibercept only arm)

Collaborators and Investigators

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

Sponsor

4D Molecular Therapeutics

Investigators

  • Study Director: Demi Dang, 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)

December 9, 2021

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

January 1, 2031

Study Registration Dates

First Submitted

January 5, 2022

First Submitted That Met QC Criteria

January 5, 2022

First Posted (Actual)

January 19, 2022

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4D-150-C001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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