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

NCT ID: NCT05197270

Last Updated: 2025-09-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

215 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-09

Study Completion Date

2031-01-31

Brief Summary

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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.

Detailed Description

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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 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).

Conditions

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Neovascular (Wet) Age-Related Macular Degeneration

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

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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.

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

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.

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

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.

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

4D-150 Dose Expansion Control

Aflibercept at a fixed regimen will be administered.

Group Type ACTIVE_COMPARATOR

Aflibercept IVT

Intervention Type BIOLOGICAL

Commercially available Active Comparator Other Name: Eylea

4D-150 Steroid Optimization

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

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

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.

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

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.

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

4D-150 Population Extension Dose 3

4D-150 will be administered at the assigned dose

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type 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 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

4D-150 Vector Shedding Dose

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

Group Type EXPERIMENTAL

4D-150 IVT

Intervention Type BIOLOGICAL

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

Interventions

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4D-150 IVT

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

Intervention Type BIOLOGICAL

Aflibercept IVT

Commercially available Active Comparator Other Name: Eylea

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

S-1. ≥50 years of age S-2. Diagnosed with macular CNV secondary to AMD S-3. BCVA ETDRS Snellen equivalent between \~20/640 and 20/25 S-5. Currently receiving anti-VEGF and has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening

Exclusion Criteria

\-


* Any condition preventing visual acuity improvement in the study eye
* Prior treatment with photodynamic therapy or retinal laser in the study eye
* History of uveitis in either eye
* Any other pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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4D Molecular Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patricia Isabell Manalastas, MD

Role: STUDY_DIRECTOR

4D Molecular Therapeutics

Locations

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Barnet Delaney Perkins Eye Center

Phoenix, Arizona, United States

Site Status RECRUITING

California Retina Consultants

Oxnard, California, United States

Site Status RECRUITING

Retinal Consultants Medical Group

Sacramento, California, United States

Site Status RECRUITING

Colorado Retina Associates

Lakewood, Colorado, United States

Site Status RECRUITING

Rand Eye Institute

Deerfield Beach, Florida, United States

Site Status RECRUITING

Vitreo Retinal Associates

Gainesville, Florida, United States

Site Status RECRUITING

Florida Eye Associates

Melbourne, Florida, United States

Site Status RECRUITING

Retinal Specialty Institute

Pensacola, Florida, United States

Site Status RECRUITING

Retina Vitreous Associates of Florida

Tampa, Florida, United States

Site Status RECRUITING

University Retina and Macula Associates

Oak Forest, Illinois, United States

Site Status RECRUITING

Retina Partners Midwest

Carmel, Indiana, United States

Site Status RECRUITING

Cumberland Valley Retina Consultants

Hagerstown, Maryland, United States

Site Status RECRUITING

Ophthalmic Consultants of Boston & Boston Eye Surgery and Laser Center

Boston, Massachusetts, United States

Site Status RECRUITING

Sierra Eye Associates

Reno, Nevada, United States

Site Status RECRUITING

Western Carolina Retinal Associates

Asheville, North Carolina, United States

Site Status WITHDRAWN

Verum Research, LLC

Eugene, Oregon, United States

Site Status RECRUITING

Mid Atlantic Retina

Bethlehem, Pennsylvania, United States

Site Status RECRUITING

Palmetto Retina Center, LLC

West Columbia, South Carolina, United States

Site Status RECRUITING

Tennessee Retina

Nashville, Tennessee, United States

Site Status RECRUITING

Austin Clinical Research

Austin, Texas, United States

Site Status RECRUITING

Valley Retina Institute, PA

McAllen, Texas, United States

Site Status RECRUITING

Retina Consultants of Texas

The Woodlands, Texas, United States

Site Status WITHDRAWN

Pacific Northwest Retina LLC

Bellevue, Washington, United States

Site Status WITHDRAWN

Emanuelli Research and Development Center, LLC

Arecibo, Puerto Rico, Puerto Rico

Site Status RECRUITING

Countries

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United States Puerto Rico

Central Contacts

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4DMT Patient Advocacy

Role: CONTACT

(888) 748-8881

Facility Contacts

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Dallin Stuart

Role: primary

Annette Beltran-Almaza

Role: primary

Rashin Sedighi

Role: primary

Lindsay Harrigan

Role: primary

Damian Stega

Role: primary

Jing Zhang

Role: primary

Melissa Dougherty

Role: primary

Vera Watkins, R.N.

Role: primary

Kimberly Velez

Role: primary

Cindy Vallejo

Role: primary

Lorraine White

Role: primary

Emma Melvin

Role: primary

Quinn Hogan

Role: primary

Huma Khan

Role: primary

Lillian Carroll

Role: primary

Leah Kritzwiser

Role: primary

Pamala Tims

Role: primary

Lisa Walden

Role: primary

Ivana Gunderson

Role: primary

Yesenia Salinas

Role: primary

Diane Perez

Role: primary

Other Identifiers

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4D-150-C001

Identifier Type: -

Identifier Source: org_study_id

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