A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP

Phase 2

Recruiting

• Conditions: X-Linked Retinitis Pigmentosa
• Interventions: Biological: rAAV2tYF-GRK1-hRPGRco; Drug: Control

• Registration Number: NCT04850118
• Lead Sponsor: Beacon Therapeutics

Brief Summary

This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501/laruparetigene zovaparvovec )) to an untreated control group in male participants with X-linked retinitis pigmentosa caused by RPGR mutations.

Detailed Description

This study is a randomized, controlled, masked, multi-center study evaluating and comparing 2 doses of AGTC-501 to an untreated control group. A single subretinal injection of AGTC-501 Dose 1 or Dose 2 will be administered in participants in 2 treatment groups while participants in the untreated control group will be followed and evaluated, after which they will be evaluated to determine eligibility to receive treatment with AGTC-501 Dose 2.

Approximately 75 eligible male participants between 12 and 50 years of age (inclusive) will be randomized in a 1:1:1 ratio to 1 of 3 groups.

Study Timeline

• Study First Submitted: 2021-04-05
• Study First Submitted QC: 2021-04-14
• Study First Posted: 2021-04-20
• Study Start: 2024-03-14
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2025-08
• Study Completion: 2029-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 75

Inclusion Criteria

1. Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Participants who provide assent must have a parent, guardian, or legal representative provide written informed consent.

2. Be between 12 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).

3. Be male (XY chromosome) and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene.

4. Have a clinical diagnosis of XLRP.

5. Be able and willing, as assessed by the Investigator, to follow study instructions, complete study assessments, comply with the protocol, and attend study visits for the duration of the study.

   Ocular Inclusion Criteria (Study Eye):

6. Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200)

7. Have a LLVA ≤64 letters (approximately Snellen 20/50) in the study eye

8. Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant's reliability, and fixation, in the study eye per the Investigator's discretion.

9. Have an LLD of > 10 letters in the study eye

10. Have detectable baseline mean macular sensitivity measured by MAIA microperimetry, between 1-12 decibels (dB) in the study eye, as determined by the Investigator and confirmed by the CRC with fixation loss ≤20% at each screening visit.

11. Have a detectable sub-foveal EZ line in the study eye as assessed by spectral domain-optical coherence tomography (SD-OCT) and confirmed by the CRC.

General

Exclusion Criteria

1. Have other known disease-causing mutations documented in the participant'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.

2. For participants 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.

3. Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.

4. Have used anti-coagulant agents that may alter coagulation

5. Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening. Corticosteroids used on an as-needed basis administered by insufflation, inhalation or local administration to the skin

6. If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.

7. Are currently participating or recently participated in any other research

8. Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.

9. Have significant media opacity impacting evaluation of the retina or vitreous. administration.

10. Had intraocular surgery within 90 days of study treatment administration.

11. Have any active ocular/intraocular infection or inflammation

12. Have a history of corticosteroid-induced raised IOP of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.

13. Have any artificial retinal implant or prosthesis.

14. Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality SD-OCT images.

15. Have any history of rhegmatogenous retinal detachment.

16. Have myopia (spherical equivalent) exceeding -10 diopters (or axial length of >30 mm if the Principal Investigator [PI] deems it appropriate to measure) or presence of pathologic myopia in the study eye.

17. Have passed the Low Contrast Ora-VNC mobility course at ≤0.35 lux light level in either eye or binocularly at any screening visit.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Dose	rAAV2tYF-GRK1-hRPGRco	Male participants 12-50 years of age treated by subretinal injection with the of AGTC-501
Group 3: Control	Control	Male participants 12-50 years of age in the untreated control group. Participants in the control group will be followed for a minimum of 24 months. After all participants have reached Month 12, participants in the control group will be given the option to receive the study drug in the fellow eye, if eligible.
Group 2: Dose	rAAV2tYF-GRK1-hRPGRco	Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501

Primary Outcome Measures

Name	Time	Method
The proportion of participants with a ≥15 letter increase from baseline in LLVA	Day 0 - Month 12	LLVA(Low Luminance Visual Acuity) will be determined by adding a neutral density filter to the refraction using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart

Secondary Outcome Measures

Name	Time	Method
Change from baseline in LLVA (First Key Secondary Endpoint)	Day 0 - Month 12	Functional vision will be determined by adding a neutral density filter to the refraction using standard ETDRS (Early Treatment of Diabetic Retinopathy) visual acuity or tumbling "E" chart
Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Second Key Secondary Endpoint) microperimetry	Day 0 - Month 12	As assessed by MAIA (Macular Integrity Assessment) microperimetry - assess photoreceptor function under low-light
Change from baseline in full-field stimulus threshold (FST) (Third Key Secondary Endpoint)	Day 0 - Month 12	Full-field stimulus threshold (FST) measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived

Trial Locations

Locations (24)

Retina Macula Institute of Arizona; 🇺🇸 Scottsdale, Arizona, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

University of Florida Health Jacksonville, Department of Ophthalmology; 🇺🇸 Jacksonville, Florida, United States

Bascom Palmer Eye Institute- University of Miami; 🇺🇸 Miami, Florida, United States

Midwest Eye Institute (Retina Partners Midwest); 🇺🇸 Carmel, Indiana, United States

Wilmer Eye Institute at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Ophthalmic Consultants of Boston; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Duke Eye Center; 🇺🇸 Durham, North Carolina, United States

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

Cole Eye Institute - Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

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

The Center for Advanced Retinal & Ocular Therapeutics University of Pennsylvania Perelman School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Mid Atlantic Retina; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Retina Consultants of Texas; 🇺🇸 Bellaire, Texas, United States

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

Baylor Eye Institute; 🇺🇸 Houston, Texas, United States

Retina Consultants of San Antonio Texas; 🇺🇸 San Antonio, Texas, United States

Sydney Eye Hospital; 🇦🇺 Sydney, New South Wales, Australia

Royal Victorian Eye & Ear Hospital; 🇦🇺 East Melbourne, Victoria, Australia

Moorfields Eye Hospital; 🇬🇧 London, United Kingdom

The Retina Clinic London, Institute of Ophthalmology, University College London; 🇬🇧 London, United Kingdom

Oxford Eye Hospital; 🇬🇧 Oxford, United Kingdom