Clinical Trials

Inclusion Criteria:

• Provide written informed consent or assent (per local regulation), prior to the conduct of any study-related procedure. Subjects who provide assent must have a parent, guardian, or legal representative provide written informed consent.
• Be between 8 and 50 years of age (inclusive) at the time of informed consent and assent (as applicable).
• Be male and have at least one documented pathogenic or likely pathogenic variant in the RPGR gene within exons 1-14 and/or ORF15 from PreventionGenetics, a CLIA-certified 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 hematology and clinical chemistry evaluations 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 study visits for the duration of the study.
• If the subject 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 subject, as required.

Ocular Inclusion Criteria (Study Eye):

• Have a BCVA no better than 75 letters (20/32) and no worse than 35 letters (20/200) in the study eye based on an ETDRS chart at each screening visit.
  • Pediatric subjects unable to read the ETDRS letters may utilize a tumbling “E” chart for BCVA assessments.
• Be able to perform all tests of visual and retinal function and structure based on the subject’s reliability, and fixation, in the study eye per the investigator’s discretion.
• Have detectable baseline mean macular sensitivity measured by (MAIA) microperimetry, between 1-12 dB in the study eye, as determined by the investigator and confirmed by the Central Reading Center (CRC), at each screening visit.
• Have detectable EZ line as assessed by SD-OCT in the study eye and confirmed by the CRC.

Exclusion Criteria:

• Have other known disease-causing mutations documented in the subject’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 subjects 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 complicating systemic diseases (e.g., medical conditions causing immunosuppression, active systemic infection) that would preclude the gene transfer or ocular surgery.
• Have known sensitivity or allergy to systemic corticosteroids or other immunosuppressive medications.
• Have used anti-coagulant agents that may alter coagulation (e.g., warfarin, heparin, apixaban, or high dose DHA [fish oil]) within 7 days prior to study treatment administration (ibuprofen, aspirin, or similar are acceptable).
• Have received any vaccination/immunization within 28 days prior to screening and/or during screening with the exception of the influenza vaccine. Subjects should be excluded if they have received the influenza vaccine within 28 days prior to randomization.
• Have used systemic corticosteroids or other immunosuppressive medications within 3 months prior to screening and/or intend to use during screening.
• If sexually active or planning to become sexually active, are unwilling to use barrier contraception for 3 months following treatment administration.
• Have any other condition or reason that, in the opinion of both the Medical Monitor and the investigator, would prevent a subject from completing study assessments during the course of the study.
• Have any other condition or reason that, in the opinion of both the Medical Monitor and the investigator, makes the subject unsuitable for the study.
• Are currently participating or recently participated in any other research protocol involving investigational agents or therapies, in the opinion of both the Medical Monitor and the investigator, would make the subject 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 AAV gene therapy product, stem cell therapy, cell-based therapy, or similar biologics.

Ocular Exclusion Criteria (Study Eye):

• Have pre-existing eye conditions 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).
• Have significant media opacity impacting evaluation of the retina or vitreous. This includes cataracts considered to be a major contributor to reducing visual acuity and/or if the subject is likely to require cataract extraction within 3 months of study treatment administration.
• Had intraocular surgery within 90 days of study treatment administration.
• Have any active ocular/intraocular infection or inflammation (e.g., severe blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, idiopathic or autoimmuneassociated uveitis, or herpetic lesions).
• Have a history of steroid-induced raised IOP of > 25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
• Have any artificial retinal implant or prosthesis.
• Have highly variable baseline mean macular sensitivity of > 2 dB between any of the 3 microperimetry assessments performed during screening.
• Have absence of clear ocular media and/or inadequate pupil dilation to facilitate good quality SD-OCT images.
• Have any history of rhegmatogenous retinal detachment.
• Have spherical equivalent > -10 diopters (D) of myopia, or absolute axial length beyond 30 mm at the investigator’s or surgeon’s discretion.

Eligibility last updated 8/13/21. Questions regarding updates should be directed to the study team contact.