4D-125 in Patients With X-Linked Retinitis Pigmentosa (XLRP)

NCT04517149 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 4D-125-C001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase 1/2 multicenter study with two parallel parts: an observational natural history cohort and an open-label, prospective interventional trial in males with non-syndromic X-linked retinitis pigmentosa (XLRP) due to mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR).

Conditions

X-Linked Retinitis Pigmentosa

Keywords

XLRP; Gene therapy

Outcome Measures

Primary Outcomes (1)

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

  24 months to 60 Months

Study Arms (3)

4D-125 Dose Exploration

EXPERIMENTAL

Dose 1 and Dose 2 4D-125 will be administered at the assigned dose level as a single dose, IVT injection on Day 1. The contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent.

Biological: 4D-125 IVT Injection

4D-125 Dose Expansion

EXPERIMENTAL

4D-125 will be administered at the assigned dose level as a single dose, IVT injection on Day 1 in both adults and pediatric participants. For adult participants only, the contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent.

Biological: 4D-125 IVT Injection

Observational

OTHER

Natural History

Other: Observational

Interventions

4D-125 IVT Injection BIOLOGICAL

4D-125 drug product developed for gene therapy, which comprises an AAV capsid variant (4D-R100) carrying a codon-optimized human Retinitis Pigmentosa GTPase Regulator transgene.

4D-125 Dose Expansion; 4D-125 Dose Exploration

Observational OTHER

Natural History

Observational

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, ≥ 6 years of age at the time of informed consent
• Hemizygous non-syndromic RPGR mutation confirmed by genetic testing
• Male, ≥12 years of age
• Hemizygous non-syndromic RPGR mutation confirmed by genetic testing
• Phase 1 Dose Exploration: At least one eye amenable to IVT injection and BCVA ≤ 78 ETDRS letters (\~20/32) and ≥ 34 ETDRS letters (\~20/200)
• Phase 2 Dose Expansion: At least one eye amenable to IVT injection AND both eyes must have BCVA ≥ 34 ETDRS letters (\~20/200)

You may not qualify if:

• Patient has previously received any AAV treatment
• Pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints

Sponsors & Collaborators

• 4D Molecular Therapeutics: lead

Study Sites (8)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Vitreo Retinal Associates

Gainesville, Florida, 32607, United States

Location

University of Michigan Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Columbia University Medical Center/Edward Harkness Eye Institute

New York, New York, 10032, United States

Location

Duke University Eye Center/Dept. of Ophthalmology

Durham, North Carolina, 27710, United States

Location

Casey Eye Institute, Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

University of Utah John A. Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Interventions

Watchful Waiting

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Schonmei Lee, MD

  4D Molecular Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Phase 1, up to 2 dose exploration cohorts will be enrolled; each cohort will initially recruit up to 3 patients to receive a single uniocular IVT injection of 4D-125 in a standard 3+3 design. The cohort will be expanded in the event of a dose limiting toxicity (DLT). Any cohort may be expanded by an additional 3 subjects (to a maximum of 12 patients) to provide additional safety information and/or to confirm the selected dose for expansion. Once the dose level has been selected, the Phase 2 Dose Expansion Cohort will be opened to dose an additional 6-12 adult patients, and includes a pediatric sub-population of up to 6 patients. For adult participants only, the contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent.

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 18, 2020
• Study Start: June 9, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)