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
- Interventions
- Registration Number
- NCT06275620
- Lead Sponsor
- Beacon Therapeutics
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- Male
- Target Recruitment
- 24
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Group 3 (High Dose, Modified Corticosteroid) AGTC-501 (high dose and modified corticosteroid regimen) Following a pars plana vitrectomy, the previously untreated eye of participants (n=approximately 3-6) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. Participants in Group 3 (high dose, modified corticosteroid) will have a more rapid corticosteroid taper. Group 1 (High Dose, Standard Corticosteroid) AGTC-501 (high dose and standard corticosteroid regimen) Following a pars plana vitrectomy, the previously untreated eye of participants (n=up to 12) will receive a central subretinal injection at the high dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks. Group 2 (Low Dose, Standard Corticosteroid) AGTC-501 (low dose and standard corticosteroid regimen) Following a pars plana vitrectomy, the previously untreated eye of participants (n=6) will receive a central subretinal injection at the low dose in the study eye at the Baseline visit; no treatment will be administered in the previously treated fellow eye. The corticosteroid taper for all treated participants in Groups 1 and 2 (high and low doses with standard corticosteroid regimen) will be a standard taper over the course of several weeks.
- Primary Outcome Measures
Name Time Method The primary safety outcome is the number of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs). Day 0 - Month 12 The primary safety outcome is the proportion of participants experiencing Grade 3 or higher local (ocular) or non-ocular treatment-emergent adverse events, including treatment-emergent serious adverse events (SAEs). Day 0 - Month 12
- Secondary Outcome Measures
Name Time Method Change from baseline in seven domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ) Day 0 - Month 12 Change from baseline in Ora-VNC (visual navigation course) mobility test score Day 0 - Month 12 As assessed by functional assessment Ora-VNC (visual navigation course) mobility course
The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. Day 0 - Month 12 The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. Day 0 - Month 12 Change from baseline in mean sensitivity across the whole grid, as measured by MAIA (Macular Integrity Assessment) microperimetry, assess photoreceptor function under low light Day 0 - Month 12 Response, as measured by MAIA (Macular Integrity Assessment) microperimetry, where response is defined as a greater than or equal to 7 decibel (dB) visual sensitivity improvement from baseline in at least 5 loci. Day 0 - Month 12 Change from baseline in full-field stimulus threshold (FST) Day 0 - Month 12 As assessed by full-field stimulus threshold (FST); FST measures the sensitivity of the visual field by testing for the lowest luminance flash which elicits a visual sensation perceived
Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity Day 0 - Month 12 Change from baseline in Low Luminance Visual Acuity (LLVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity Day 0 - Month 12 Proportion of responding eyes in treated versus control eyes at Month 12 where responder is defined as an improvement of at least 15-letters on low-luminance visual acuity (LLVA) Day 0 - Month 12 Change from baseline in ellipsoid zone (EZ) area measured by spectral domain optical coherence tomography (SD OCT) Day 0 - Month 12 Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score Day 0 - Month 12 As measured by the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course
Trial Locations
- Locations (7)
University of Florida
🇺🇸Jacksonville, Florida, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Retina Foundation of the Southwest
🇺🇸Dallas, Texas, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States