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

NCT06333249 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AGTC-RPGR-001 SKYLINE
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 6

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.

Conditions

X-Linked Retinitis Pigmentosa

Keywords

XLRP; retinal degeneration; RPGR; adeno-associated virus; gene therapy; AAV

Outcome Measures

Primary Outcomes (1)

• The difference in the proportion of responding eyes between treated and control eyes in the low dose group and high dose group at 12 months, as measured by MAIA microperimetry, where response is defined as a 7dB or more improvement in at least 5 loci.

  Day 0 - Month 12

Secondary Outcomes (11)

• Proportion of responding eyes in treated eyes versus control eyes in the low dose group and the high dose group at Month 12 where responder is defined as an ORA-VNC mobility test score improvement of 2 or more luminance levels.

  Day 0 - Month 12

• Proportion of responding eyes in treated versus control eyes in the low dose group and the high dose group at Month 12, as measured by MAIA microperimetry, where responder is defined as a 7 dB or more improvement in at least 5 loci within bleb.

  Day 0 - Month 12

• Proportion of responding eyes in treated vs control eyes in the low dose group and the high dose group at Month 12, measured by MAIA microperimetry where responder is defined as 7 dB or more improvement in at least 5 loci within the central 16 loci

  Day 0 - Month 12

• Difference in mean change from baseline in the central 36 loci (C36) mean sensitivity, as measured by MAIA microperimetry, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.

  Day 0 - Month 12

• Difference in mean change from baseline in "within bleb" mean sensitivity, as measured by MAIA microperimetry, in treated eyes versus control eyes in the low dose group and high dose group at Month 12.

  Day 0 - Month 12

Study Arms (2)

Low Dose Group

EXPERIMENTAL

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.

Biological: rAAV2tYF-GRK1-RPGR

High Dose Group

EXPERIMENTAL

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.

Biological: rAAV2tYF-GRK1-RPGR

Interventions

rAAV2tYF-GRK1-RPGR BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

High Dose Group; Low Dose Group

Eligibility Criteria

• Age: 8 Years - 50 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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):
• Have history of oral or genital herpes and unable and/or unwilling to utilize prophylactic antiviral medication.
• Have a history of ocular herpes.
• 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 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.

Sponsors & Collaborators

• Beacon Therapeutics: lead

Study Sites (6)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Boston Children's Hosptial

Boston, Massachusetts, 02115, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• 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.

  PMID: 40547876 DERIVED

MeSH Terms

Conditions

Retinal Degeneration

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Phase 2 study is a masked study; therefore, neither the investigator nor the subject will know the dose assignment. Both the subject and the investigator will know which eye received treatment. Masking will continue until the Month 12 data analysis is performed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The purpose of the Phase 2 study is to evaluate the efficacy, safety, and tolerability of two doses of AGTC-501 in male subjects between 8 - 50 years of age (inclusive) with XLRP genetically confirmed by at least one pathogenic variant in the RPGR gene. Approximately 12 subjects who meet the inclusion criteria, will be randomized in a 1:1 ratio to 1 of 2 treatment groups. Each subject will receive the assigned dose of AGTC-501 in the study eye; no treatment will be administered in the fellow eye. As treatment outcomes in pediatric vs. adult subjects may differ, randomization to dose groups will be stratified by age. Each subject will receive a central subretinal injection of AGTC-501 at the assigned dose in the central macula of the study eye.

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: March 27, 2024
• Study Start: April 13, 2021
• Primary Completion: April 11, 2023
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 12, 2024

Record last verified: 2024-08

Locations

US (6)