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

NCT04850118 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AGTC-RPGR-002
• Study Type: interventional
• Target: 85
• Locations: 3 countries
• Sites: 24

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.

Conditions

X-Linked Retinitis Pigmentosa

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change from baseline in LLVA (First Key Secondary Endpoint)

  Day 0 - Month 12

• Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Second Key Secondary Endpoint) microperimetry

  Day 0 - Month 12

• Change from baseline in full-field stimulus threshold (FST) (Third Key Secondary Endpoint)

  Day 0 - Month 12

Other Outcomes (1)

• Number and proportion of treatment-emergent ocular/non-ocular adverse events

  Day 0 - Year 5

Study Arms (3)

Group 1: Dose

ACTIVE COMPARATOR

Male participants 12-50 years of age treated by subretinal injection with the of AGTC-501

Biological: rAAV2tYF-GRK1-hRPGRco

Group 2: Dose

ACTIVE COMPARATOR

Male participants 12-50 years of age treated by subretinal injection with the dose of AGTC-501

Biological: rAAV2tYF-GRK1-hRPGRco

Group 3: Control

OTHER

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

Interventions

rAAV2tYF-GRK1-hRPGRco BIOLOGICAL

Adeno-associated virus vector expressing a human RPGR gene

Also known as: AGTC-501

Group 1: Dose; Group 2: Dose

Control DRUG

Untreated Control Group 3

Also known as: Untreated Control Group

Group 3: Control

Eligibility Criteria

• Age: 12 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. Participants who provide assent must have a parent, guardian, or legal representative provide written informed consent.
• Be between 12 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
• Be male (XY chromosome) and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene.
• Have a clinical diagnosis of XLRP.
• 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.
• Have a BCVA ≤ 78 letters (approximately Snellen, 20/32) and ≥ 34 letters (approximately Snellen, 20/200)
• Have a LLVA ≤64 letters (approximately Snellen 20/50) in the study eye
• 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.
• Have an LLD of \> 10 letters in the study eye
• 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.
• 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.

You may not qualify if:

• 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.
• For participants 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 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. Corticosteroids used on an as-needed basis administered by insufflation, inhalation or local administration to the skin
• If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.
• Are currently participating or recently participated in any other research
• Have previously received any AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.
• Have significant media opacity impacting evaluation of the retina or vitreous. administration.
• Had intraocular surgery within 90 days of study treatment administration.
• Have any active ocular/intraocular infection or inflammation
• Have a history of corticosteroid-induced raised IOP of \>25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.

Sponsors & Collaborators

• Beacon Therapeutics: lead

Study Sites (24)

Retina Macula Institute of Arizona

Scottsdale, Arizona, 85255, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of Florida Health Jacksonville, Department of Ophthalmology

Jacksonville, Florida, 32209, United States

Location

Bascom Palmer Eye Institute- University of Miami

Miami, Florida, 33136, United States

Location

Midwest Eye Institute (Retina Partners Midwest)

Carmel, Indiana, 46290, United States

Location

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke Eye Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Cole Eye Institute - Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Casey Eye Institute, OHSU

Portland, Oregon, 97239, United States

Location

The Center for Advanced Retinal & Ocular Therapeutics University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15219, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

Baylor Eye Institute

Houston, Texas, 77030, United States

Location

Retina Consultants of San Antonio Texas

San Antonio, Texas, 78240, United States

Location

Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

Location

Royal Victorian Eye & Ear Hospital

East Melbourne, Victoria, 3002, Australia

Location

Moorfields Eye Hospital

London, EC1V 2PD, United Kingdom

Location

The Retina Clinic London, Institute of Ophthalmology, University College London

London, W1G7LB, United Kingdom

Location

Oxford Eye Hospital

Oxford, OX39DU, United Kingdom

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 Officials

• Carrie Reichley

  Beacon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For groups 1 and 2 (AGTC-501 dosing groups), both the participants and the Investigators are masked to dose assignment, and only the unmasked staff who prepare the dose are unmasked to the participants dose assignment. Due to the need to perform the subretinal injection to administer the study drug, both participants and Investigators will know whether the participant was assigned to a treatment group or to the control group. To minimize bias of the treated and control study eye evaluations, starting at Month 3, microperimetry, and BCVA/LLVA assessments will be conducted by appropriately qualified masked evaluators who do not know whether the participant underwent surgery. Participants will be instructed not to disclose whether they had surgery to the examiner administering the test.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomized in a 1:1:1 ratio to 1 of 3 groups (high dose, low dose, untreated) control. After 12 months, participants in the untreated group will be evaluated to determine eligibility to receive the high dose of AGTC-501.

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 20, 2021
• Study Start: March 14, 2024
• Primary Completion: August 1, 2025
• Study Completion (Estimated): October 1, 2029
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); AU (2); US (19)