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

4D Molecular Therapeutics (4DMT)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: X-Linked Retinitis Pigmentosa

Treatments: Biological: 4D-125 IVT Injection; Other: Observational

Study type: Interventional

Funder types: Industry

Identifiers

NCT04517149

4D-125-C001

Details and patient eligibility

About

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).

Full 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.

Enrollment: 21 patients

Sex: Male

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 3 patient groups

4D-125 Dose Exploration

Experimental group

Description:

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.

Treatment:

Biological: 4D-125 IVT Injection

4D-125 Dose Expansion

Experimental group

Description:

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.

Treatment:

Biological: 4D-125 IVT Injection

Observational

Other group

Description:

Natural History

Treatment:

Other: Observational