Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

X-Linked Retinitis Pigmentosa Clinical Trial

— HORIZON  

Official title:

A Phase 1/2 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) and a Phase 2 Randomized, Controlled, Masked, Multi-center Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03316560
• Other study ID #: AGTC-RPGR-001 HORIZON
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 16, 2018
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Beacon Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations.

Description:

This protocol includes a non-randomized, open-label, Phase 1/2 study (HORIZON). Approximately 30 participants will be enrolled into the dose escalation study (HORIZON). Each participant will receive the study agent by subretinal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). There are a total of 15 visits over approximately 36 months, and long-term follow-up evaluations annually at years 4 and 5.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. completion date: March 2025
• Est. primary completion date: November 9, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 50 Years

Eligibility

Phase 1/2 Dose Escalation Inclusion Criteria:

• Male subjects with a documented RPGR mutation
• Clinical diagnosis of X-linked retinitis pigmentosa (XLRP)
• Best-corrected visual acuity not better than 78 ETDRS letters (20/32) in the study eye;
• Ability to perform tests of visual and retinal function and structure and ability to comply with other research procedures;
• Detectable baseline mean macular sensitivity, as measured by microperimetry.
• Have detectable Ellipsoid Zone (EZ) line during the pre-treatment period as assessed by OCT and confirmed by the CRC.

Phase 1/2 Dose Escalation Exclusion Criteria:

• Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or increase the risk of surgical complications (for example, glaucoma, corneal or lenticular opacities, diabetic retinopathy, retinal vasculitis);
• Use of anti-coagulant agents that may alter coagulation within 7 days prior to study agent administration;
• Use of systemic corticosteroids or other immunosuppressive medications within 3 months prior to enrollment;
• Any other condition that would prevent a subject from completing follow-up examinations during the course of the study;
• Any other condition or reason that, in the opinion of the investigator, makes the subject unsuitable for the study;
• Previous receipt of any AAV gene therapy product;
• Monocular or having BCVA less than 20/800 in the fellow eye

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa
• X-Linked Retinitis Pigmentosa

Intervention

Biological:
• rAAV2tYF-GRK1-RPGR
Adeno-associated virus vector expressing a human RPGR gene

Locations

Country	Name	City	State
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Casey Eye Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Beacon Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and proportion of Adverse Events	Number and proportion of participants experiencing Grade 3 or higher local (ocular) or systemic treatment-emergent adverse events that occur during the 36 months after study agent administration; number and proportion of participants experiencing treatment-emergent AEs, including treatment-emergent serious AEs;	Day 0 - Month 36
Primary	Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters.		Day 0 - Month 36
Secondary	Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye		Day 0 - Month 36
Secondary	Changes from baseline in visual acuity		Day 0 - Month 36
Secondary	Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT)		Day 0 - Month 36
Secondary	Changes from baseline in quality of life questionnaire responses		Day 0 - Month 36
Secondary	Change from baseline in visual function by light-adapted perimetry		Day 0 - Month 36
Secondary	Change from baseline in fundus imaging		Day 0 - Month 36
Secondary	Change from baseline in full-field light sensitivity threshold (FST)		Day 0 - Month 36
Secondary	Changes from baseline in visual function by dark-adapted full field perimetry (for subjects treated peripherally)		Day 0 - Month 36