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

January 10, 2024 updated by: 4D Molecular Therapeutics

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

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Florida
      • Gainesville, Florida, United States, 32607
        • Vitreo Retinal Associates
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan Kellogg Eye Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center/Edward Harkness Eye Institute
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Eye Center/Dept. of Ophthalmology
    • Oregon
      • Portland, Oregon, United States, 97239
        • Casey Eye Institute, Oregon Health and Science University
    • Texas
      • Dallas, Texas, United States, 75231
        • Retina Foundation of the Southwest

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.
Experimental: 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.
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
Other: Observational
Natural History

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

4D Molecular Therapeutics

Investigators

  • Study Director: Schonmei Lee, MD, 4D Molecular Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 9, 2020

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

August 14, 2020

First Submitted That Met QC Criteria

August 14, 2020

First Posted (Actual)

August 18, 2020

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 10, 2024

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4D-125-C001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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