A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE)

NCT ID: NCT06333249

Last Updated: 2024-08-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-13
• Study Completion Date: 2027-02-28

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

Approximately 12 participants, who were not part of the Phase 1/2 (HORIZON) study, will be enrolled into the dose expansion portion of the study. These participants will be randomized in a 1:1 ratio to 1 of 2 treatment groups (i.e., Group 1 [low dose] and Group 2 [high dose]). Each participant will receive the assigned dose of AGTC-501 in one eye on a single occasion.

Conditions

X-Linked Retinitis Pigmentosa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Low Dose Group

Male subjects at least 8 y/o treated with a lower dose (Dose 2 in RPGR-001 Horizon Phase 1/2 study) of rAAV2tYF-GRK1-RPGR study drug.

Group Type: EXPERIMENTAL

rAAV2tYF-GRK1-RPGR

Intervention Type: BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

High Dose Group

Male subjects at least 8 y/o treated with a higher dose (Dose 5 in RPGR-001 Horizon Phase 1/2 study) 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

• Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Subjects who provide assent must have a parent, guardian, or legal representative provide written informed consent.
• Be between 8 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
• Be male and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene
• Have a clinical diagnosis of XLRP.
• Have a BCVA no better than 75 letters and no worse than 35 letters based on an ETDRS chart at each screening visit.
• Be able to perform all tests of visual and retinal function and structure in both eyes based on the subject's reliability, and fixation, per the investigator's discretion.
• Have detectable baseline mean macular sensitivity measured by (MAIA) microperimetry, as determined by the investigator and confirmed by the Central Reading Center (CRC).
• Have detectable EZ line in both eyes as assessed by SD-OCT and confirmed by the CRC.

Exclusion Criteria

• Have other known disease-causing mutations documented in the subject's medical history or identified through a retinal dystrophy gene panel, that in the opinion of the investigator would interfere with the potential therapeutic effect of the study agent or the quality of the assessments.
• For subjects with herpes simplex virus (HSV):

1. Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.

2. Have a history of ocular herpes.

3. Have active oral or genital herpes or are currently receiving treatment for HSV infection.

• Have complicating systemic diseases (e.g., medical conditions causing immunosuppression, active systemic infection) that would preclude the gene transfer or ocular surgery.
• Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
• Have used anti-coagulant agents that may alter coagulation
• Have received any vaccination/immunization within 28 days prior to screening and/or during screening with the exception of the influenza vaccine, which is only exclusionary if they have received the influenza vaccine within 28 days prior to randomization.
• Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening.
• Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.

• Have pre-existing eye conditions that would preclude the planned surgery, interfere with the interpretation of study endpoints, or increase the risk of surgical complications
• Have significant media opacity impacting evaluation of the retina or vitreous.
• Had intraocular surgery within 90 days of study treatment administration.
• Have any active ocular/intraocular infection or inflammation
• Have a history of steroid-induced raised IOP of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
• Have any artificial retinal implant or prosthesis.
• Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality OCT images.
• Have any history of rhegmatogenous retinal detachment.
• Have myopia (spherical equivalent) exceeding -10 diopters (or axial length of >30 mm if PI deems it appropriate to measure) or presence of pathologic myopia in the study eye.
• Have passed the Low Contrast Ora-VNC™ mobility course in either eye or binocularly at any screening visit.

• Minimum Eligible Age: 8 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

University of Florida

Jacksonville, Florida, United States

Boston Children's Hosptial

Boston, Massachusetts, United States

Cincinnati Eye Institute

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, 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)

Other Identifiers

AGTC-RPGR-001 SKYLINE

Identifier Type: -

Identifier Source: org_study_id