A Phase 1/2/3, Open-Label, Dose Escalation, Dose Expansion and Randomized, Controlled Study to Evaluate the Safety and Efficacy of ATSN-201 Gene Therapy in Subjects With RS1-Associated X-linked Retinoschisis (LIGHTHOUSE)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 97
- 试验地点
- 28
- 主要终点
- Safety and tolerability as assessed by dose-limiting toxicities and treatment-emergent adverse events
研究概览
简要总结
This study will evaluate the safety and efficacy of ATSN-201 in subjects ≥ 6 years of age with RS1-associated X-linked retinoschisis (XLRS).
详细描述
The study is designed in three parts: a dose escalation phase (Part A), a dose expansion phase (Part B) and a randomized, controlled phase (Part C).
In Part C of the study, eligible patients who enroll in this study will be randomly assigned to be treated with ATSN-201 or to have no treatment; subjects assigned to ATSN-201 will receive the drug as a one-time subretinal injection of ATSN-201 in one eye or both eyes, depending on whether only one or both eyes meet criteria for treatment. Subjects will have regular assessments for 1 year as part of the Main Study Period and additional assessments over the next 4 years as part of the Extension Study Period.
Some subjects may have all their study visits at a surgery site.
Some subjects may go to one study site (a medical site) to determine eligibility and another study site (a surgery site) to have surgery - including pre-operative care and approximately 1-week of post-operative care per treated eye. After the surgery, they will go back to the other study site (the medical site) to complete the follow-up visits.
Subjects who do not receive treatment as part of the control group can choose to receive ATSN-201 in one or both eyes after the 1-year Main Study Period if eligible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Cohort 4 will be partially masked. Cohort 6 will be partially masked.
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A and B:
- •Inclusion Criteria:
- •Age ≥ 18 for Cohorts 1 through 4, and age ≥ 6 years and < 18 years for Cohort
- •Male patients with clinical diagnosis of XLRS caused by mutations in RS
- •Best corrected visual acuity (BCVA) in study eye of 34 to 73 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (corresponding to a Snellen acuity of 20/200 to 20/40).
- •Presence of foveal schisis and /or parafoveal/perifoveal schisis in the study eye on SD-OCT per the Principal Investigator.
排除标准
- •Pre-existing eye conditions in the study eye that would contribute significantly to an increased risk of visual loss from a subretinal injection (eg, advanced glaucoma, optic neuropathy, uveitis, corneal transplants).
- •Any intraocular surgery (including laser treatment) in the study eye within 6 months prior to Screening or any intraocular surgery anticipated in the study eye during the first 12 months of the study.
- •Treatment in a prior ocular gene or cell therapy study.
- •Inclusion Criteria:
- •Note: For patients ineligible for bilateral dosing based on the ocular exclusion criteria, the same eye must meet all ocular inclusion criteria, but none of the ocular exclusion criteria, to be eligible for unilateral dosing.
- •General All of the following criteria must be met for unilateral or bilateral dosing.
- •Age ≥ 6 years.
- •Genetically male patients with clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1 OR Genetically female patients with clinical diagnosis of XLRS caused by biallelic pathogenic or likely pathogenic mutations in RS
- •Ocular At least 1 eye must meet all of the following criteria for both unilateral and bilateral dosing.
- •BCVA of 34 to 73 ETDRS letters (corresponding to a Snellen acuity of 20/200 to 20/40).
- •Presence of foveal schisis on SD-OCT.
- •Exclusion Criteria:
- •General None of the following criteria can be met for unilateral or bilateral dosing.
- •Treatment with any carbonic anhydrase inhibitor (oral or topical) within 1 month prior to Screening.
- •Treatment in a prior ocular gene or cell therapy study.
- •Absence of macular schisis.
- •BCVA better than 75 ETDRS letters (corresponding to a Snellen acuity of 20/32).
- •Pre-existing eye conditions that would contribute significantly to an increased risk of visual loss from a subretinal injection (eg, advanced glaucoma, optic neuropathy, uveitis, corneal transplants).
- •Any intraocular surgery (including laser treatment) within 6 months prior to Screening or any intraocular surgery anticipated during the first 12 months of the study.
研究组 & 干预措施
Cohort 5, Pediatric
干预措施: ATSN-201 (Biological)
Cohort 6, Treatment
干预措施: ATSN-201 (Biological)
Cohort 1, Low Dose
干预措施: ATSN-201 (Biological)
Cohort 3, Mid Dose
干预措施: ATSN-201 (Biological)
Cohort 4, Control
Cohort 2, High Dose
干预措施: ATSN-201 (Biological)
Cohort 4, High Volume
干预措施: ATSN-201 (Biological)
Cohort 6, Control
Cohort 4, Low Volume
干预措施: ATSN-201 (Biological)
结局指标
主要结局
Safety and tolerability as assessed by dose-limiting toxicities and treatment-emergent adverse events
时间窗: From baseline to week 52
Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs).
Part A (Dose Escalation) and Part B (Dose Expansion): Safety and tolerability as assessed by dose-limiting toxicities and treatment-emergent adverse events
时间窗: From baseline to week 52
Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs).
Part C (Phase 3, Randomized, Controlled) Effect of ATSN-201 on visual function.
时间窗: From baseline to week 52
Proportion of subjects ≥12 years of age with improvement ≥ 7dB from baseline in microperimetry across prespecified loci in the study eye.
次要结局
- Visual function as assessed by full-field electroretinogram parameters(From baseline to week 52)
- Subject-reported visual function as assessed by the NEI VFQ-25 in adult subjects(From baseline to week 52)
- Visual acuity as assessed by low-luminance visual acuity(From baseline to week 52)
- Visual function as assessed by static perimetry(From baseline to week 52)
- Visual function as assessed by microperimetry(From baseline to week 52)
- Macular structure as assessed by spectral domain optical coherence tomography(From baseline to week 52)
- Visual acuity as assessed by best-corrected visual acuity(From baseline to week 52)
- Visual function as assessed by contrast sensitivity(From baseline to week 52)
- Macular structure as assessed by fundus autofluorescence(From baseline to week 52)
- Subject-reported visual function as assessed by the CVAQC in pediatric subjects(From baseline to week 52)
- Part A and Part B: Visual acuity as assessed by best-corrected visual acuity(From baseline to week 52)
- Part A and Part B: Visual acuity as assessed by low-luminance visual acuity(From baseline to week 52)
- Part A and Part B: Visual function as assessed by contrast sensitivity(From baseline to week 52)
- Part A and Part B: Visual function as assessed by microperimetry(From baseline to week 52)
- Part A and Part B: Macular structure as assessed by spectral domain optical coherence tomography(From baseline to week 52)
- Part A and Part B: Macular structure as assessed by fundus autofluorescence(From baseline to week 52)
- Part A and Part B: Subject-reported visual function as assessed by the NEI VFQ-25 in adult subjects(From baseline to week 52)
- Part A and Part B: Subject-reported visual function as assessed by the CVAQC in pediatric subjects(From baseline to week 52)
- Part A and Part B: Subject-reported visual function as assessed by the MRDQ in subjects 13 years of age or greater.(From baseline to week 52)
- Part C: Macular structure as assessed by spectral domain optical coherence tomography(From baseline to week 52)
- Part C: Visual acuity as assessed by best-corrected visual acuity or low-luminance visual acuity(From baseline to week 52)
- Part C: Visual acuity as assessed by best-corrected visual acuity as measured by Early Treatment Diabetic Retinopathy Study chart(From baseline to week 52)
- Part C: Visual acuity as assessed by low luminance visual acuity as measured by Early Treatment Diabetic Retinopathy Study chart(From baseline to week 52)
- Part C: Visual function as assessed by microperimetry(From baseline to week 52)
- Part C: Functional vision as assessed by reading speed(From baseline to week 52)
- Part C: Subject-reported visual function as assessed by the MRDQ in subjects 13 years of age or greater(From baseline to week 52)
- Part C: Subject-reported visual function as assessed by the CVAQC in pediatric subjects(From baseline to week 52)
- Part C: Subject perception of change and severity (PGIC/PGIS)(From baseline to week 52)
- Part C: Evaluate the safety of ATSN-201(From baseline to week 52)