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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04517149
Recruitment Status : Active, not recruiting
First Posted : August 18, 2020
Last Update Posted : January 31, 2023
Sponsor:
Information provided by (Responsible Party):
4D Molecular Therapeutics

Study Description
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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).

Condition or disease Intervention/treatment Phase
X-Linked Retinitis Pigmentosa Biological: 4D-125 IVT Injection Other: Observational Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 9, 2020
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : May 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.
Observational
Natural History
 Other: Observational
Natural History


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

Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04517149


Locations
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United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Vitreo Retinal Associates
Gainesville, Florida, United States, 32607
United States, Michigan
University of Michigan Kellogg Eye Center
Ann Arbor, Michigan, United States, 48105
United States, New York
Columbia University Medical Center/Edward Harkness Eye Institute
New York, New York, United States, 10032
United States, North Carolina
Duke University Eye Center/Dept. of Ophthalmology
Durham, North Carolina, United States, 27710
United States, Oregon
Casey Eye Institute, Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Texas
Retina Foundation of the Southwest
Dallas, Texas, United States, 75231
United States, Utah
University of Utah John A. Moran Eye Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
4D Molecular Therapeutics
Investigators
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Study Director: Schonmei Lee, MD 4D Molecular Therapeutics
More Information
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Responsible Party: 4D Molecular Therapeutics
ClinicalTrials.gov Identifier: NCT04517149    
Other Study ID Numbers: 4D-125-C001
First Posted: August 18, 2020    Key Record Dates
Last Update Posted: January 31, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by 4D Molecular Therapeutics:
XLRP
Gene therapy
Additional relevant MeSH terms:
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Retinitis
Retinitis Pigmentosa
Retinal Diseases
Eye Diseases
 Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn