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
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 24
- 试验地点
- 7
- 主要终点
- 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).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Group 1 (High Dose, Standard Corticosteroid)
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.
干预措施: AGTC-501 (high dose and standard corticosteroid regimen) (Biological)
Group 2 (Low Dose, Standard Corticosteroid)
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.
干预措施: AGTC-501 (low dose and standard corticosteroid regimen) (Biological)
Group 3 (High Dose, Modified Corticosteroid)
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.
干预措施: AGTC-501 (high dose and modified corticosteroid regimen) (Biological)
结局指标
主要结局
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).
时间窗: 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).
时间窗: Day 0 - Month 12
次要结局
- Change from baseline in Best Corrected Visual Acuity (BCVA) using Early-Treatment Diabetic Retinopathy Study (ETDRS) visual acuity(Day 0 - Month 12)
- 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)
- 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 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)
- Change from baseline in the MObility Standardized Test-Virtual Reality (MOST-VR) mobility course test score(Day 0 - Month 12)