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

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ClinicalTrials.gov Identifier: NCT04517149
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : June 15, 2021
Sponsor:
Information provided by (Responsible Party):
4D Molecular Therapeutics

Tracking Information
First Submitted Date  ICMJE August 14, 2020
First Posted Date  ICMJE August 18, 2020
Last Update Posted Date June 15, 2021
Actual Study Start Date  ICMJE June 9, 2020
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2021)		 Primary outcome measure [ Time Frame: 24 months ]
Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2020)		 Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]
Incidence and severity of TEAEs and SAEs, including clinically significant changes in safety parameters.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 4D-125 in Patients With X-Linked Retinitis Pigmentosa (XLRP)
Official Title  ICMJE 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
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 retinitis pigmentosa GTPase regulator (RPGR).
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.

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. Secondary endpoints will assess preliminary efficacy measures at 12 months after 4D-125 administration.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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 9 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 patients.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE X-Linked Retinitis Pigmentosa
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: 4D-125 Dose Exploration

    Dose 1 and Dose 2

    4D-125 will be administered at the assigned dose level as a single dose, uniocular IVT injection on Day 1.

    Intervention: Biological: 4D-125 IVT Injection
  • Experimental: 4D-125 Dose Expansion
    4D-125 will be administered at the assigned dose level as a single dose, uniocular IVT injection on Day 1.
    Intervention: Biological: 4D-125 IVT Injection
  • Observational
    Natural History
    Intervention: Other: Observational
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 27, 2021)		 43
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2020)		 37
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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, ≥18 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Olivia Lam 510-902-2065 clinicaltrials@4DMT.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04517149
Other Study ID Numbers  ICMJE 4D-125-C001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party 4D Molecular Therapeutics
Study Sponsor  ICMJE 4D Molecular Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert Kim, MD 4D Molecular Therapeutics
PRS Account 4D Molecular Therapeutics
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP