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

NCT ID: NCT03316560

Last Updated: 2024-05-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-16
• Study Completion Date: 2025-03-31

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.

Conditions

X-Linked Retinitis Pigmentosa

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: Phase 1/2 Dose Escalation

Male subjects at least 18 y/o treated with Dose 1 of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 2: Phase 1/2 Dose Escalation

Male subjects at least 18 y/o treated with Dose 2 of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 3 Phase 1/2 Dose Escalation

Group 3 male subjects at least 18 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 4 Phase 1/2 Dose Escalation

Group 4 male subjects at least 6 y/o treated with Dose 3 of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 5 Phase 1/2 Dose Escalation

Male subjects at least 18 y/o treated with Dose 5 of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Group 6 Phase 1/2 Dose Escalation

Male subjects at least 18 y/o treated with Dose 6 of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Interventions

rAAV2tYF-GRK1-RPGR

Adeno-associated virus vector expressing a human RPGR gene

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Beacon Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Duke University

Durham, North Carolina, United States

Cincinnati Eye Institute

Cincinnati, Ohio, United States

Casey Eye Institute

Portland, Oregon, United States

Retina Foundation of the Southwest

Dallas, Texas, United States

Countries

United States

References

Wang CY, Chen L, Lin TY, Huang SP. Systematic Identification of Candidate Genes for Inherited Retinal Disease Gene Therapy Integrating Worldwide IRD Cohort and Single-Cell Analysis. J Ophthalmol. 2025 Jun 12;2025:7014745. doi: 10.1155/joph/7014745. eCollection 2025.

Reference Type: DERIVED

PMID: 40547876 (View on PubMed)

Alibhai AY, De Pretto LR, Yaghy A, Woo KM, Dos Santos Xilau NR, Siddiqui H, Pandiscio CA, Homer A, Curtiss D, Waheed NK. Comparing the Thin Plate Spline and Gaussian Interpolation Methods in Generating Hill of Visions for X-Linked Retinitis Pigmentosa Patients. Transl Vis Sci Technol. 2024 Dec 2;13(12):26. doi: 10.1167/tvst.13.12.26.

Reference Type: DERIVED

PMID: 39680391 (View on PubMed)

Other Identifiers

AGTC-RPGR-001 HORIZON

Identifier Type: -

Identifier Source: org_study_id