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

NCT05197270 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 4D-150-C001
• Study Type: interventional
• Target: 215
• Locations: 2 countries
• Sites: 25

Brief Summary

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.

Conditions

Neovascular (Wet) Age-Related Macular Degeneration

Keywords

Age-related macular degeneration; AMD; Exudative AMD; Exudative age-related macular degeneration; Neovascular AMD; Neovascular age-related macular degeneration; Wet age-related macular degeneration; Wet macular degeneration; Wet AMD; wAMD; Retinal gene therapy; Intravitreal gene therapy; Genetic Medicine; Ocular Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in safety parameters

  52 weeks

Secondary Outcomes (6)

• Time to receiving the first supplemental aflibercept injection

  52 weeks

• Percentage of subjects requiring supplemental aflibercept injections over 52 weeks

  52 weeks

• Number of supplemental aflibercept injections over 52 weeks

  52 weeks

• Change from baseline in BCVA over time (up to 52 weeks) as assessed using the ETDRS Visual Acuity Chart

  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)

  52 weeks

Study Arms (10)

4D-150 Dose Escalation up to 4 dose levels

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 Dose Expansion Dose 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 Dose Expansion Dose 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 Dose Expansion Control

ACTIVE COMPARATOR

Aflibercept at a fixed regimen will be administered.

Biological: Aflibercept IVT

4D-150 Steroid Optimization

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 Population Extension Dose 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 Population Extension Dose 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 Population Extension Dose 3

EXPERIMENTAL

4D-150 will be administered at the assigned dose

Biological: 4D-150 IVT

4D-150 Contralateral Eye Dose

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 Vector Shedding Dose

EXPERIMENTAL

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Biological: 4D-150 IVT

Interventions

4D-150 IVT BIOLOGICAL

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

4D-150 Contralateral Eye Dose; 4D-150 Dose Escalation up to 4 dose levels; 4D-150 Dose Expansion Dose 1; 4D-150 Dose Expansion Dose 2; 4D-150 Population Extension Dose 1; 4D-150 Population Extension Dose 2; 4D-150 Population Extension Dose 3; 4D-150 Steroid Optimization; 4D-150 Vector Shedding Dose

Aflibercept IVT BIOLOGICAL

Commercially available Active Comparator Other Name: Eylea

4D-150 Dose Expansion Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥50 years of age
• Diagnosed with CNV secondary to AMD (confirmed by reading center)
• BCVA ≥34 ETDRS letters (\~20/200) in the contralateral eye, and BCVA in the study eye:
• 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):
• Study eye amenable to IVT injection
• Ability to perform tests of visual and retinal function and structure, and ability to comply with other protocol-specified procedures
• 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
• 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
• Medical records available to document history of anti-VEGF therapy (dates, drugs, and dosage) for a minimum of 12 months prior to Screening
• Provide written informed consent.
• Contralateral Eye Sub-study-Specific Criteria:
• 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.
• 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)
• 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)

Sponsors & Collaborators

• 4D Molecular Therapeutics: lead

Study Sites (25)

Barnet Delaney Perkins Eye Center

Phoenix, Arizona, 85016, United States

RECRUITING

California Retina Consultants

Oxnard, California, 93036, United States

RECRUITING

Retinal Consultants Medical Group

Sacramento, California, 95841, United States

RECRUITING

Colorado Retina Associates

Lakewood, Colorado, 80288, United States

RECRUITING

Rand Eye Institute

Deerfield Beach, Florida, 33064, United States

SUSPENDED

Retina Vitreous Consultants, LLP DBA Retina Group of Florida

Fort Lauderdale, Florida, 33308, United States

ACTIVE NOT RECRUITING

Vitreo Retinal Associates

Gainesville, Florida, 32607, United States

RECRUITING

Florida Eye Associates

Melbourne, Florida, 32901, United States

RECRUITING

Retinal Specialty Institute

Pensacola, Florida, 32503, United States

RECRUITING

Retina Vitreous Associates of Florida

Tampa, Florida, 33607, United States

RECRUITING

University Retina and Macula Associates

Oak Forest, Illinois, 60452, United States

RECRUITING

Retina Partners Midwest

Carmel, Indiana, 46290, United States

RECRUITING

Cumberland Valley Retina Consultants

Hagerstown, Maryland, 21740, United States

RECRUITING

Ophthalmic Consultants of Boston & Boston Eye Surgery and Laser Center

Boston, Massachusetts, 02114, United States

RECRUITING

Sierra Eye Associates

Reno, Nevada, 89502, United States

RECRUITING

Western Carolina Retinal Associates

Asheville, North Carolina, 28803, United States

WITHDRAWN

Verum Research, LLC

Eugene, Oregon, 97401, United States

RECRUITING

Mid Atlantic Retina

Bethlehem, Pennsylvania, 18017, United States

RECRUITING

Palmetto Retina Center, LLC

West Columbia, South Carolina, 29169, United States

RECRUITING

Tennessee Retina

Nashville, Tennessee, 37203, United States

RECRUITING

Austin Clinical Research

Austin, Texas, 78750, United States

RECRUITING

Valley Retina Institute, PA

McAllen, Texas, 78503, United States

RECRUITING

Retina Consultants of Texas

The Woodlands, Texas, 77384, United States

WITHDRAWN

Pacific Northwest Retina LLC

Bellevue, Washington, 98004, United States

WITHDRAWN

Emanuelli Research and Development Center, LLC

Arecibo, Puerto Rico, 00612, Puerto Rico

RECRUITING

MeSH Terms

Conditions

Macular Degeneration; Wet Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Officials

• Demi Dang, MD

  4D Molecular Therapeutics

  STUDY DIRECTOR

Central Study Contacts

4DMT Patient Advocacy

CONTACT

(888) 748-8881; clinicaltrials@4DMT.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Dose Escalation will be open-label. During Dose Expansion, outcome assessors will be masked to treatment assignment. Other site personnel (including investigator) and subjects will be unmasked to treatment assignment but will be masked to 4D-150 dose level. The Sponsor and its representatives and the site dose preparer/pharmacist will be unmasked to treatment assignment. Steroid Optimization and Population Extension will be open-label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Dose Escalation, the safety and tolerability of multiple dose levels of 4D-150 will be examined following an open-label, 3+3 dose escalation design (n=3-5 per dose level). In Dose Expansion, subjects (n=50) will be randomized to receive one of 2 dose levels of 4D-150 (n=20 for each dose level) based on results from Dose Escalation, or aflibercept (n=10). In Steroid Optimization (n=up to 96) and Population Extension (n=up to 45) Cohorts, subjects will be assigned sequentially to receive 4D-150 at doses cleared by the DSMC. Contralateral sub-study: Up to 20 subjects from the 4D-150-C001 trial who have previously received 4D-150 in study eye-1 will be enrolled and administered a single open-label IVT injection of 4D-150 in the contralateral eye. Vector Shedding sub-study: Approximately 15 subjects will receive an open-label IVT injection of 4D-150 to evaluate vector shedding.

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 19, 2022
• Study Start: December 9, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): January 1, 2031
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); US (24)