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

X-Linked Retinitis Pigmentosa Clinical Trial

Official title:

An Open-label, Phase 1/2 Trial of Gene Therapy 4D-125 in Males With X-linked Retinitis Pigmentosa (XLRP) Caused by Mutations in the RPGR Gene

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04517149
• Other study ID #: 4D-125-C001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 9, 2020
• Est. completion date: May 2029

Study information

• Verified date: July 2023
• Source: 4D Molecular Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: May 2029
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

Natural History Key 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

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa
• X-Linked Retinitis Pigmentosa

Intervention

Biological:
• 4D-125 IVT Injection
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.

Other:
• Observational
Natural History

Locations

Country	Name	City	State
United States	University of Michigan Kellogg Eye Center	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Duke University Eye Center/Dept. of Ophthalmology	Durham	North Carolina
United States	Vitreo Retinal Associates	Gainesville	Florida
United States	Columbia University Medical Center/Edward Harkness Eye Institute	New York	New York
United States	Casey Eye Institute, Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
4D Molecular Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters		24 months to 60 Months