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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-09

Study Completion Date

2029-05-31

Brief Summary

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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).

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Detailed Description

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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.

Conditions

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X-Linked Retinitis Pigmentosa

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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4D-125 Dose Exploration

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.

Group Type EXPERIMENTAL

4D-125 IVT Injection

Intervention Type 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 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.

Group Type EXPERIMENTAL

4D-125 IVT Injection

Intervention Type 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.

Observational

Natural History

Group Type OTHER

Observational

Intervention Type OTHER

Natural History

Interventions

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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.

Intervention Type BIOLOGICAL

Observational

Natural History

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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

Minimum Eligible Age

12 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No