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

A Randomized, Controlled, Masked, Multi-center Study Evaluating the Efficacy, Safety, and Tolerability of Two Doses of AGTC-501 Compared to an Untreated Control Group in Male Participants With X-linked Retinitis Pigmentosa

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.

Study Overview

• Status: Active, not recruiting
• Conditions: X-Linked Retinitis Pigmentosa
• Intervention / Treatment: Biological: rAAV2tYF-GRK1-hRPGRco; Drug: Control

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 Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Sydney Eye Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Royal Victorian Eye & Ear Hospital
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A3J1
      • McGill University Health Centre - Glen Site
• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital
  • London, United Kingdom, W1G7LB
    • The Retina Clinic London, Institute of Ophthalmology, University College London
  • Oxford, United Kingdom, OX39DU
    • Oxford Eye Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85255
      • Retina Macula Institute of Arizona
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Jacksonville, Department of Ophthalmology
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute- University of Miami
  • Indiana
    • Carmel, Indiana, United States, 46290
      • Midwest Eye Institute (Retina Partners Midwest)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Eye Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Cleveland, Ohio, United States, 44195
      • Cole Eye Institute - Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute, OHSU
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
    • Philadelphia, Pennsylvania, United States, 19104
      • The Center for Advanced Retinal & Ocular Therapeutics University of Pennsylvania Perelman School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15219
      • University of Pittsburgh
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest
    • Houston, Texas, United States, 77030
      • Baylor Eye Institute
    • San Antonio, Texas, United States, 78240
      • Retina Consultants of San Antonio Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

General 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Dose; Male participants 12-50 years of age treated by subretinal injection with the of AGTC-501	Biological: rAAV2tYF-GRK1-hRPGRco; Adeno-associated virus vector expressing a human RPGR gene; Other Names: AGTC-501
Active Comparator: Group 2: Dose; Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501	Biological: rAAV2tYF-GRK1-hRPGRco; Adeno-associated virus vector expressing a human RPGR gene; Other Names: AGTC-501
Other: Group 3: 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.	Drug: Control; Untreated Control Group 3; Other Names: Untreated Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with a ≥15 letter increase from baseline in LLVA	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	Day 0 - Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in LLVA (First Key Secondary Endpoint)	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	Day 0 - Month 12
Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Second Key Secondary Endpoint) microperimetry	As assessed by MAIA (Macular Integrity Assessment) microperimetry - assess photoreceptor function under low-light	Day 0 - Month 12
Change from baseline in full-field stimulus threshold (FST) (Third Key Secondary Endpoint)	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	Day 0 - Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and proportion of treatment-emergent ocular/non-ocular adverse events	Ocular/non-ocular adverse events are collected the duration of the trial	Day 0 - Year 5

Collaborators and Investigators

• Sponsor: Beacon Therapeutics
• Investigators: Study Director: Carrie Reichley, Beacon Therapeutics

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 31, 2031

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: retinal degeneration; gene therapy; AAV; adeno-associated virus; XLRP; RPGR
• Additional Relevant MeSH Terms: Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration
• Other Study ID Numbers: AGTC-RPGR-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No