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.

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.

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.

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.