A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN)

Launched by BEACON THERAPEUTICS · Feb 16, 2024

Keywords

ClinConnect Summary

This is a Phase 2, open‑label (everyone knows what treatment is given), non‑randomized study testing how safe a gene therapy called AGTC‑501 is in men with X‑linked Retinitis Pigmentosa caused by RPGR mutations. The study uses a single subretinal injection into the eye that has not been treated before. There are three groups: Group 1 gets a high dose with a standard corticosteroid (anti‑inflammatory) plan, Group 2 gets a low dose with the same steroid plan, and Group 3 gets a high dose with a modified steroid taper. The main goal is to see whether the treatment causes any safety problems over the first year, with longer follow‑up planned for up to five years.

Who may be eligible and what to expect: to join, you must be male and 12 years or older, have one eye that was previously treated with a RPGR gene therapy, and have a certain level of vision (neither too good nor too poor) and the ability to do tests of vision and retina function. You must not have other conditions that could interfere with the study, recent eye surgery, an active eye infection, or a history of steroid‑induced high eye pressure. If enrolled, you will have a single eye injection and follow‑up visits for about a year (with additional long‑term follow‑up). A data safety review will happen after early participants to decide whether to proceed to Group 3. The study is being conducted at multiple U.S. centers, with up to about 24 participants in total.

Gender

MALE

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.