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

Phase 1

Recruiting

• Conditions: Neovascular (Wet) Age-Related Macular Degeneration
• Interventions: Biological: 4D-150 IVT; Biological: Aflibercept IVT

• Registration Number: NCT05197270
• Lead Sponsor: 4D Molecular Therapeutics

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.

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 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 Timeline

• Study Start: 2021-12-09
• Study First Submitted: 2022-01-05
• Study First Submitted QC: 2022-01-05
• Study First Posted: 2022-01-19
• Status Verified: 2025-06
• Last Update Submitted: 2025-09-09
• Last Update Posted: 2025-09-15
• Primary Completion: 2027-03
• Study Completion: 2031-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 215

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

Shedding Sub-study-specific

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
4D-150 Dose Escalation up to 4 dose levels	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Dose Expansion Dose 1	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Dose Expansion Dose 2	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Dose Expansion Control	Aflibercept IVT	Aflibercept at a fixed regimen will be administered.
4D-150 Steroid Optimization	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Population Extension Dose 1	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Population Extension Dose 2	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Population Extension Dose 3	4D-150 IVT	4D-150 will be administered at the assigned dose
4D-150 Contralateral Eye Dose	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
4D-150 Vector Shedding Dose	4D-150 IVT	4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Primary Outcome Measures

Name	Time	Method
Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in safety parameters	52 weeks

Secondary Outcome Measures

Name	Time	Method
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
Percent Change in Annualized Mean Number of anti-VEGF IVT injections before and after the 4D-150 injection	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)

Trial Locations

Locations (24)

Barnet Delaney Perkins Eye Center; 🇺🇸 Phoenix, Arizona, United States

California Retina Consultants; 🇺🇸 Oxnard, California, United States

Retinal Consultants Medical Group; 🇺🇸 Sacramento, California, United States

Colorado Retina Associates; 🇺🇸 Lakewood, Colorado, United States

Rand Eye Institute; 🇺🇸 Deerfield Beach, Florida, United States

Vitreo Retinal Associates; 🇺🇸 Gainesville, Florida, United States

Florida Eye Associates; 🇺🇸 Melbourne, Florida, United States

Retinal Specialty Institute; 🇺🇸 Pensacola, Florida, United States

Retina Vitreous Associates of Florida; 🇺🇸 Tampa, Florida, United States

University Retina and Macula Associates; 🇺🇸 Oak Forest, Illinois, United States

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