A Phase 2 Open-label Study to Evaluate the Safety of Laruparetigene Zovaparvovec Administered Bilaterally in Male Participants With X-Linked Retinitis Pigmentosa

NCT07174726 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RPGR-005 Landscape
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this Phase 2 Study is to see if the investigational study drug, laruparetigene zovaparvovec, also known as AGTC-501, given in both eyes, is safe and works to preserve and/or improve vision and other symptoms of XLRP.

Conditions

X-Linked Retinitis Pigmentosa (XLRP)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The number and percentage of participants experiencing Grade 3 or higher ocular or non-ocular treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (SAEs), at Month 12

  Day 0 - Month 12

Secondary Outcomes (11)

• The number and percentage of participants experiencing ocular or non-ocular TEAEs, including treatment-emergent SAEs during the Study period

  Day 0-5 years

• Change from baseline in low-luminance visual acuity (LLVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity at Month 12

  Day 0 - Month 12

• Change from baseline in mean sensitivity across the whole grid, as measured by macular integrity assessment (MAIA) microperimetry at Month 12

  Day 0 - Month 12

• Response, as measured by MAIA microperimetry, where response is defined as a ≥ 7 dB visual sensitivity improvement from baseline in at least 5 loci at Month 12

  Day 0 - Month 12

• Change from baseline in full-field stimulus threshold (FST) at Month 12

  Day 0 - Month 12

Study Arms (1)

Participants undergo pars plana vitrectomy and receive a central subretinal administration both eyes

EXPERIMENTAL

On Day 1, participants will undergo a pars plana vitrectomy and receive a central subretinal administration of laruparetigene zovaparvovec in their first treated study eye. For the first six participants, participants will undergo a pars plana vitrectomy followed by a central subretinal administration of laruparetigene zovaparvovec in their second eye between 30 and 60 days after the first surgery. Once the first six study participants have been dosed in both eyes, the interval between dosing of the first and second eye may be reduced to a minimum of 7 days (and up to 14 days) for up to four of the remaining participants enrolled in the study, provided the following conditions are met: * No unexpected safety concerns were observed following dosing of the first eye. * An independent safety review by the Sponsor, Investigator, and DSMC Chair confirms that bilateral dosing may proceed.

Biological: Adeno-associated virus vector expressing a human RPGR gene

Interventions

Adeno-associated virus vector expressing a human RPGR gene BIOLOGICAL

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

Participants undergo pars plana vitrectomy and receive a central subretinal administration both eyes

Eligibility Criteria

• Age: 12 Years - 50 Years
• Gender Eligibility Details: Male
• 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 procedures. 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 providing informed consent and assent (as applicable)
• Be male (XY chromosome) and have at least 1 documented pathogenic or likely pathogenic variant in the RPGR gene, within exons 1-14 and/or ORF15, from an appropriately certified or accredited laboratory
• Have a clinical diagnosis of XLRP
• Be in good general health to withstand subretinal surgery and perioperative medications based on a complete physical examination and results from hematology, chemistry, and coagulation analyses performed at screening
• Be able and willing, as assessed by the Investigator, to follow study instructions, complete study assessments, comply with the protocol, and attend all study visits
• If the participant has a parent or caregiver, the parent or caregiver must be able to follow study instructions, comply with the protocol, and attend study visits with the participant, as required
• Have an LLVA ≤ 64 letters (approximately Snellen, 20/50) in both eyes based on an ETDRS chart at each screening visit. Participants unable to read the ETDRS letters may use a tumbling "E" chart for the LLVA assessments
• Have an LLD of \>10 letters
• Be able to perform all tests of visual and retinal function and structure in both eyes based on the participant's reliability and fixation, per the Investigator's discretion
• Have a detectable mean macular sensitivity by MAIA microperimetry at baseline between 1 and 12 dB in both eyes, as determined by the Investigator and confirmed by the central reading center (CRC), with a fixation loss ≤ 20% at each screening visit
• Have a detectable sub-foveal EZ line as assessed by SD-OCT in both eyes as 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 drug or the quality of the assessments
• For participants with herpes simplex virus (HSV):
• Have a history of oral or genital herpes and be unable and/or unwilling to use a prophylactic antiviral medication.
• Have a history of ocular herpes.
• Have active oral or genital herpes or are currently receiving treatment for active HSV infection
• Have complicating systemic diseases (e.g., medical conditions causing immunosuppression, autoimmunity, active systemic infection) that would preclude the gene transfer or ocular surgery if not adequately managed or treated
• Have a known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications
• Have used anticoagulant agents that may alter coagulation (e.g., warfarin, heparin, apixaban, or high-dose docosahexaenoic acid \[fish oil\]) within 7 days prior to study drug administration (ibuprofen, aspirin, or similar agents are acceptable
• If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following study drug administration
• Have any other condition or reason that, in the opinion of the Investigator, would prevent the participant from completing all study assessments
• Have any other condition or reason that, in the opinion of the Investigator, makes the participant unsuitable for the study
• Are currently participating or recently participated in any other research protocol involving investigational agents or therapies that, in the opinion of the Investigator, would make the participant unsuitable for the study. Recent participation is defined as participation within 90 days of initial screening for this study OR within 10 half-lives of the investigational drug, whichever is longer
• Have previously received any adeno-associated virus (AAV) gene therapy product, stem cell therapy, cell-based therapy, or similar biologics
• Have pre-existing eye conditions in either eye that would preclude the planned surgery, interfere with the interpretation of study endpoints, or increase the risk of surgical complications (e.g., corneal opacities, diabetic retinopathy, retinal vasculitis, glaucoma, active cystoid macular edema)
• Have significant media opacity impacting evaluation of the retina or vitreous in either eye. This includes cataracts considered to be a major contributor to reducing visual acuity and/or if the participant is likely to require cataract extraction within 3 months of study drug administration

Sponsors & Collaborators

• Beacon Therapeutics: lead

Study Sites (6)

University of Florida Jacksonville Ophthalmology

Jacksonville, Florida, 32209, United States

RECRUITING

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

NOT YET RECRUITING

Duke Eye Center

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

RECRUITING

OHSU Casey Eye Institute

Portland, Oregon, 97239, United States

RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

MeSH Terms

Conditions

Retinal Degeneration

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Study Officials

• None None

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Serva Health Serva Health

CONTACT

855-467-2364; ProviderSupport@scenictrials.com

Amy Christenson

CONTACT

medical@beacontx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To evaluate the long-term safety and tolerability of laruparetigene zovaparvovec administered bilaterally via subretinal injection

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: September 16, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 15, 2030
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)