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

• ClinicalTrials.gov Identifier: NCT05197270
• Recruitment Status: Recruiting
• First Posted: January 19, 2022
• Last Update Posted: February 16, 2024
• Sponsor: 4D Molecular Therapeutics
• Information provided by (Responsible Party): 4D Molecular Therapeutics

Tracking Information

• First Submitted Date: January 5, 2022
• First Posted Date: January 19, 2022
• Last Update Posted Date: February 16, 2024
• Actual Study Start Date: December 9, 2021
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 5, 2022): 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 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 5, 2022)

• Time to receiving the first supplemental aflibercept injection [ Time Frame: 52 weeks ]
• Percentage of subjects requiring supplemental aflibercept injections over 52 weeks [ Time Frame: 52 weeks ]
• Number of supplemental aflibercept injections over 52 weeks [ Time Frame: 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 ]
• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration
• Official Title: 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
• 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 Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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 40) and Population Extension (n=up to 45) Cohorts, subjects will be assigned sequentially to receive 4D-150 at doses cleared by the DSMC.

Masking: Single (Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment

• Condition: Neovascular (Wet) Age-Related Macular Degeneration

Intervention

• Biological: 4D-150 IVT
  4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept
• Biological: Aflibercept IVT
  Commercially available Active Comparator Other Name: Eylea

Study Arms

• 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.
  Intervention: Biological: 4D-150 IVT
• 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.
  Intervention: Biological: 4D-150 IVT
• 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.
  Intervention: Biological: 4D-150 IVT
• Active Comparator: 4D-150 Dose Expansion Control
  Aflibercept at a fixed regimen will be administered.
  Intervention: Biological: Aflibercept IVT
• Experimental: 4D-150 Steroid Optimization
  4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
  Intervention: Biological: 4D-150 IVT
• 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.
  Intervention: Biological: 4D-150 IVT
• 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.
  Intervention: Biological: 4D-150 IVT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 29, 2023): 150
• Original Estimated Enrollment (submitted: January 5, 2022): 65
• Estimated Study Completion Date: November 2025
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: 4DMT Patient Advocacy; (888) 748-8881; clinicaltrials@4DMT.com

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT05197270
• Other Study ID Numbers: 4D-150-C001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: 4D Molecular Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: 4D Molecular Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chyong Nien, MD; 4D Molecular Therapeutics

• PRS Account: 4D Molecular Therapeutics
• Verification Date: August 2023