a study comparing two doses of agtc-501 in male participants with x-linked retinitis pigmentosa caused by rpgr mutations (dawn)

Conditions: X-Linked Retinitis Pigmentosa

Summary: this phase 2 study is a non-randomized, open-label, study of the safety of agtc-501 in participants with xlrp who have previously been treated with a full-length aav vector-based gene therapy targeting rpgr protein.

this is a phase 2, open-label, multicenter study to evaluate the safety of 2 doses of agtc-501 administered as a single subretinal injection in participants with xlrp who have previously been treated with a full-length aav vector-based gene therapy targeting rpgr protein. the trial includes a screening period of up to 60 days and a 5 year study period. each participant will receive a single subretinal injection of one of two dose levels of agtc-501 in their previously untreated eye. there will be 3 groups. group 1 will receive the high dose and include up to 12 participants, group 2 will receive the low dose and will include 6 participants, and group 3 will include \~3-6 participants. participants in groups 1 and 2 will receive the standard corticosteroid regimen. a single subretinal injection of the high dose agtc-501 will be administered to participants in group 1 (n = 12), while participants in group 2 (n = 6) will receive a single subretinal injection of low dose agtc-501. group 2 (low dose agtc-501, standard steroid) will be dosed before moving to group 3. after 6 group 1 (high dose) study participants reach post-operative month 1, all data will be reviewed by the dsmc. if no safety signals arise, additional participants, group 3 (n \~ 3-6), will receive a single subretinal injection of the high dose with a modified course of corticosteroids.

Eligibility criteria:
inclusion criteria: * be ≥12 years of age * have one eye previously treated with an aav vector-based gene therapy designed to provide full-length functioning rpgr protein. * have a bcva no better than 78 letters and no worse than 34 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 detectable baseline mean macular sensitivity measured by maia microperimetry, as determined by the investigator and confirmed by the central reading center (crc). * have detectable ez line in the study eye as assessed by sd-oct and confirmed by the crc. exclusion criteria: * 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. * 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 * had intraocular surgery within 90 days of study treatment administration. * have any active ocular/intraocular infection or inflammation * have a history of steroid-induced raised iop of \>25 mmhg following corticosteroid exposure, despite topical iop-lowering pharmacologic therapy.

Keywords: xlrp retinal degeneration rpgr adeno-associated virus gene therapy aav