rAAV2tYF-GRK1-hRPGRco: Adeno-associated virus vector expressing a human RPGR gene
Control: Untreated Control Group 3
Study 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.
Eligibility
Sex
MALE
Min age
12 Years
Max age
50 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
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
Trial sites (25)
Facility
City
Region
Status
Retina Macula Institute of Arizona
Scottsdale
Arizona
Children's Hospital Los Angeles
Los Angeles
California
University of Florida Health Jacksonville, Department of Ophthalmology
Jacksonville
Florida
Bascom Palmer Eye Institute- University of Miami
Miami
Florida
Midwest Eye Institute (Retina Partners Midwest)
Carmel
Indiana
Wilmer Eye Institute at Johns Hopkins
Baltimore
Maryland
Ophthalmic Consultants of Boston
Boston
Massachusetts
Mayo Clinic
Rochester
Minnesota
Duke Eye Center
Durham
North Carolina
Cincinnati Eye Institute
Cincinnati
Ohio
Cole Eye Institute - Cleveland Clinic
Cleveland
Ohio
Casey Eye Institute, OHSU
Portland
Oregon
The Center for Advanced Retinal & Ocular Therapeutics University of Pennsylvania Perelman School of Medicine
Philadelphia
Pennsylvania
Mid Atlantic Retina
Philadelphia
Pennsylvania
University of Pittsburgh
Pittsburgh
Pennsylvania
Retina Consultants of Texas
Bellaire
Texas
Retina Foundation of the Southwest
Dallas
Texas
Baylor Eye Institute
Houston
Texas
Retina Consultants of San Antonio Texas
San Antonio
Texas
Sydney Eye Hospital
Sydney
New South Wales
Royal Victorian Eye & Ear Hospital
East Melbourne
Victoria
McGill University Health Centre - Glen Site
Montreal
Quebec
Moorfields Eye Hospital
London
United Kingdom
The Retina Clinic London, Institute of Ophthalmology, University College London
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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