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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04517149
Other study ID # 4D-125-C001
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date June 9, 2020
Est. completion date May 2029

Study information

Verified date July 2023
Source 4D Molecular Therapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 21
Est. completion date May 2029
Est. primary completion date June 2026
Accepts healthy volunteers No
Gender Male
Age group 12 Years and older
Eligibility 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 Design


Intervention

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

Locations

Country Name City State
United States University of Michigan Kellogg Eye Center Ann Arbor Michigan
United States University of Colorado Aurora Colorado
United States Retina Foundation of the Southwest Dallas Texas
United States Duke University Eye Center/Dept. of Ophthalmology Durham North Carolina
United States Vitreo Retinal Associates Gainesville Florida
United States Columbia University Medical Center/Edward Harkness Eye Institute New York New York
United States Casey Eye Institute, Oregon Health and Science University Portland Oregon

Sponsors (1)

Lead Sponsor Collaborator
4D Molecular Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters 24 months to 60 Months
See also
  Status Clinical Trial Phase
Completed NCT04926129 - Natural History of the Progression of X-Linked Retinitis Pigmentosa
Recruiting NCT05926583 - A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa Phase 3
Enrolling by invitation NCT06275620 - A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN) Phase 2
Completed NCT03116113 - A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112 Phase 1/Phase 2
Recruiting NCT04850118 - A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP Phase 2/Phase 3
Enrolling by invitation NCT03584165 - Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa Phase 3
Active, not recruiting NCT04312672 - Long-term Follow-up Gene Therapy Study for RPGR- XLRP
Completed NCT04868916 - An Observational Study of Japanese Participants With X-linked Retinitis Pigmentosa
Completed NCT03252847 - Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR) Phase 1/Phase 2
Recruiting NCT05874310 - Gene Therapy for Subjects With RPGR Mutation-associated X-linked Retinitis Pigmentosa Early Phase 1
Active, not recruiting NCT04671433 - Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene Phase 3
Active, not recruiting NCT04794101 - Follow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene Phase 3
Completed NCT03314207 - Clinical Evaluation of Patients With X-linked Retinitis Pigmentosa (XLRP)
Active, not recruiting NCT03316560 - Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations Phase 1/Phase 2
Active, not recruiting NCT06333249 - A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE) Phase 2