A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: AGTC-501 (high dose and standard corticosteroid regimen), AGTC-501 (low dose and standard corticosteroid regimen), AGTC-501 (high dose and modified corticosteroid regimen).
- Who it may be relevant to
- Registry conditions: X-Linked Retinitis Pigmentosa. Basic parameters: from 12 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase 1/2 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) and a Phase 2 Randomized, Controlled, Masked, Multi-center Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa
Overview
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.
Interventions
- Biological AGTC-501 (high dose and standard corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene - Biological AGTC-501 (low dose and standard corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene - Biological AGTC-501 (high dose and modified corticosteroid regimen)
Adeno-associated virus vector expressing a human RPGR gene
Primary outcome measures
- 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). [Time frame: 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). [Time frame: Day 0 - Month 12]
Secondary outcome measures (12)
- The number of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. [Time frame: Day 0 - Month 12]
- The proportion of participants experiencing treatment-emergent AEs of ocular/non-ocular adverse events, including treatment-emergent serious AEs. [Time frame: 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 [Time frame: 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. [Time frame: Day 0 - Month 12]
- Change from baseline in full-field stimulus threshold (FST) [Time frame: Day 0 - Month 12]
- Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity [Time frame: Day 0 - Month 12]
- Change from baseline in Low Luminance Visual Acuity (LLVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity [Time frame: 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) [Time frame: Day 0 - Month 12]
- Change from baseline in ellipsoid zone (EZ) area measured by spectral domain optical coherence tomography (SD OCT) [Time frame: Day 0 - Month 12]
- Change from baseline in seven domain scores from a Michigan Retinal Degeneration Questionnaire (MRDQ) [Time frame: Day 0 - Month 12]
- Change from baseline in Ora-VNC (visual navigation course) mobility test score [Time frame: Day 0 - Month 12]
- Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score [Time frame: Day 0 - Month 12]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 7 centers
- University of Florida — Jacksonville
- Bascom Palmer Eye Institute — Miami
- Boston Children's Hospital — Boston
- Cincinnati Eye Institute — Cincinnati
- Cleveland Clinic — Cleveland
- Casey Eye Institute — Portland
- Retina Foundation of the Southwest — Dallas
Publications
- Wang CY, Chen L, Lin TY, Huang SP. Systematic Identification of Candidate Genes for Inherited Retinal Disease Gene Therapy Integrating Worldwide IRD Cohort and Single-Cell Analysis. J Ophthalmol. 2025 Jun 12;2025:7014745. doi: 10.1155/joph/7014745. eCollection 2025. PMID 40547876
Identifiers
NCT: NCT06275620 · AGTC-RPGR-001 DAWN