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

Phase 1

Recruiting

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

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, 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).

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: 2024-11
• Last Update Submitted: 2024-11-01
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-11
• Study Completion: 2026-11

Recruitment & Eligibility

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

Inclusion Criteria

• ≥50 years of age
• Diagnosed with macular CNV secondary to AMD
• BCVA ETDRS Snellen equivalent for dose escalation between ~20/32 and ~20/320, or for dose expansion and population extension between ~20/25 and~20/200, for steroid optimization between ~20/25 and ~20/640
• Currently receiving anti-VEGF treatment in the study eye and has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
4D-150 Dose Expansion Control	Aflibercept IVT	Aflibercept at a fixed regimen will be administered.
4D-150 Population Extension Dose 3	4D-150 IVT	4D-150 will be administered at the assigned dose
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 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.

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
Change from baseline in BCVA over time (up to 52 weeks) as assessed using the ETDRS Visual Acuity Chart	52 weeks
Number of supplemental aflibercept injections over 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)	52 weeks

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

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

Vitreo Retinal Associates; 🇺🇸 Gainesville, 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

Retina Partners Midwest; 🇺🇸 Carmel, Indiana, United States

Cumberland Valley Retina Consultants; 🇺🇸 Hagerstown, Maryland, United States

Ophthalmic Consultants of Boston & Boston Eye Surgery and Laser Center; 🇺🇸 Boston, Massachusetts, United States

Sierra Eye Associates; 🇺🇸 Reno, Nevada, United States

Western Carolina Retinal Associates; 🇺🇸 Asheville, North Carolina, United States

Verum Research, LLC; 🇺🇸 Eugene, Oregon, United States

Mid Atlantic Retina; 🇺🇸 Bethlehem, Pennsylvania, United States

Palmetto Retina Center, LLC; 🇺🇸 West Columbia, South Carolina, United States

Tennessee Retina; 🇺🇸 Nashville, Tennessee, United States

Austin Clinical Research; 🇺🇸 Austin, Texas, United States

Valley Retina Institute, PA; 🇺🇸 McAllen, Texas, United States

Retina Consultants of Texas; 🇺🇸 The Woodlands, Texas, United States

Pacific Northwest Retina LLC; 🇺🇸 Bellevue, Washington, United States

Emanuelli Research and Development Center, LLC; 🇵🇷 Arecibo, Puerto Rico