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

Phase 1

Active, not recruiting

• Conditions: X-Linked Retinitis Pigmentosa
• Interventions: Other: Observational; Biological: 4D-125 IVT Injection

• Registration Number: NCT04517149
• Lead Sponsor: 4D Molecular Therapeutics

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).

Detailed Description

This Phase 1/2 study will gather data in an observational phase Natural History Cohort to further characterize and evaluate natural disease progression in male patients with genetically-confirmed X-linked retinitis pigmentosa (XLRP) caused by mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR). The study will also evaluate the safety and tolerability, as assessed by frequency and severity of ocular and systemic adverse events, as well as preliminary clinical efficacy of a single intravitreal (IVT) injection of 4D-125 at two dose levels in this patient population in one or both eyes (the contralateral eye dose provided the subject is eligible and provides consent).

4D-125 has been developed as a gene replacement therapy for XLRP. After receiving 4D-125, patients will be followed for 24 months with continued safety follow-up and 36 additional months of long-term follow-up. Secondary endpoints will assess preliminary efficacy measures over time after 4D-125 administration.

Study Timeline

• Study Start: 2020-06-09
• Study First Submitted: 2020-08-14
• Study First Submitted QC: 2020-08-14
• Study First Posted: 2020-08-18
• Status Verified: 2023-07
• Last Update Submitted: 2024-01-10
• Last Update Posted: 2024-01-12
• Primary Completion: 2026-06
• Study Completion: 2029-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 21

Inclusion Criteria

• Male, ≥ 6 years of age at the time of informed consent
• Hemizygous non-syndromic RPGR mutation confirmed by genetic testing

Interventional Key Inclusion Criteria:

• 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)

Key Exclusion Criteria (all cohorts)

• 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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Observational	Observational	Natural History
4D-125 Dose Exploration	4D-125 IVT Injection	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.
4D-125 Dose Expansion	4D-125 IVT Injection	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.

Primary Outcome Measures

Name	Time	Method
Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters	24 months to 60 Months

Trial Locations

Locations (7)

Columbia University Medical Center/Edward Harkness Eye Institute; 🇺🇸 New York, New York, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

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

University of Michigan Kellogg Eye Center; 🇺🇸 Ann Arbor, Michigan, United States

Duke University Eye Center/Dept. of Ophthalmology; 🇺🇸 Durham, North Carolina, United States

Casey Eye Institute, Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States