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

Phase 1

Active, not recruiting

• Conditions: X-Linked Retinitis Pigmentosa
• Interventions: Biological: rAAV2tYF-GRK1-RPGR

• Registration Number: NCT03316560
• Lead Sponsor: Beacon Therapeutics

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2017-10-10
• Study First Submitted QC: 2017-10-17
• Study First Posted: 2017-10-20
• Study Start: 2018-04-16
• Primary Completion: 2023-11-09
• Disposition First Posted: 2024-02-20
• Status Verified: 2024-05
• Disposition First Submitted: 2024-05-08
• Last Update Submitted: 2024-05-16
• Last Update Posted: 2024-05-20
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 29

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 2: Phase 1/2 Dose Escalation	rAAV2tYF-GRK1-RPGR	Male subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug.
Group 5 Phase 1/2 Dose Escalation	rAAV2tYF-GRK1-RPGR	Male subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug.
Group 6 Phase 1/2 Dose Escalation	rAAV2tYF-GRK1-RPGR	Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.
Group 3 Phase 1/2 Dose Escalation	rAAV2tYF-GRK1-RPGR	Group 3 male subjects at least 18 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.
Group 4 Phase 1/2 Dose Escalation	rAAV2tYF-GRK1-RPGR	Group 4 male subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.
Group 1: Phase 1/2 Dose Escalation	rAAV2tYF-GRK1-RPGR	Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.

Primary Outcome Measures

Name	Time	Method
Number and proportion of Adverse Events	Day 0 - Month 36	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;
Number and proportion of participants experiencing abnormal clinically relevant hematology or clinical chemistry parameters.	Day 0 - Month 36

Secondary Outcome Measures

Name	Time	Method
Changes from baseline in retinal structure as assessed by spectral-domain optical coherence tomography (SD-OCT)	Day 0 - Month 36
Change from baseline in visual function by light-adapted perimetry	Day 0 - Month 36
Change from baseline in full-field light sensitivity threshold (FST)	Day 0 - Month 36
Changes from baseline in visual function as measured by mesopic microperimetry in the treated eye compared to the untreated eye	Day 0 - Month 36
Changes from baseline in quality of life questionnaire responses	Day 0 - Month 36
Changes from baseline in visual function by dark-adapted full field perimetry (for subjects treated peripherally)	Day 0 - Month 36
Changes from baseline in visual acuity	Day 0 - Month 36
Change from baseline in fundus imaging	Day 0 - Month 36

Trial Locations

Locations (4)

Casey Eye Institute; 🇺🇸 Portland, Oregon, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Cincinnati Eye Institute; 🇺🇸 Cincinnati, Ohio, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States