A Double-Masked, Randomized, Placebo-Controlled, Paired-Eye Study to Evaluate the Efficacy, Safety and Tolerability of Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Due to the c.2991+1655A>G (p.Cys998X) Mutation in the CEP290 Gene
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 25
- 主要终点
- Change from baseline in Best-Corrected Visual Acuity (BCVA)
研究概览
简要总结
The purpose of this double-masked, randomized, placebo-controlled, paired-eye study is to evaluate the efficacy, safety and tolerability of Sepofarsen in subjects with Leber Congenital Amaurosis (LCA) due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290.
详细描述
This is a double-masked, randomized, placebo-controlled, paired-eye study in which one eye of each subject will serve as a control.
At the start of the study the two eyes of each subject will be randomized such that one eye receives sepofarsen and the other eye receives placebo for the first year. In the second year, for all subjects, the eye that was randomized to receive sepofarsen will continue to receive sepofarsen. For the eye that was randomized to placebo in the first year, treatment in the second year will be allocated, as follows: 50% of the eyes will continue to receive placebo, and 50% of the eyes will receive sepofarsen.
Sepofarsen and placebo will be administered via intravitreal injection every 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Confirmed clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation in CEP
- •Adults: >=18 years / Minors: 6 to <18 years.
- •BCVA (FrACT) equal to or worse than logMAR +0.4 (approximate Snellen equivalent 20/50) to +2.9 logMAR based on quantifiable, reliable FrACT. LP subjects with documented evidence of prior better vision eligible.
- •Symmetrical disease between the two eyes as defined by a BCVA (FrACT) within 0.2 logMAR at baseline.
- •Detectable ONL in the macular area as determined by the CRC at Screening.
排除标准
- •Mutations in genes other than the CEP290 gene associated with other IRD diseases or syndromes.
- •Presence of any ocular pathology in either eye that may make comparison of the eyes not feasible.
- •Presence of unstable concurrent CME, or subject started on (or changed dose of) topical or systemic carbonic anhydrase inhibitor treatment in the 3 months prior to enrollment. CME is allowed if stable for 3 months (with or without treatment).
- •Presence of any clinically significant lens opacities/cataracts based on the AREDS lens grading scale.
- •Any prior receipt of genetic (RNA or DNA therapy) or stem-cell therapy for ocular or non-ocular disease, including sepofarsen.
研究组 & 干预措施
Mixed - Treatment Eye - up to Month 24
Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18.
干预措施: sepofarsen (Drug)
Sepofarsen - Treatment Eye - up to Month 12
Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.
干预措施: sepofarsen (Drug)
Mixed - Fellow Eye - Month 12 to Month 24
Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18.
干预措施: sepofarsen (Drug)
Continued - Treatment Eye - up to Month 24
Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.
干预措施: sepofarsen (Drug)
Mixed - Fellow Eye - up to Month 12
Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18
Note: up to Month 12 these subjects receive placebo in the Fellow Eye, as all subjects do.
干预措施: Placebo IVT (Other)
Placebo - Fellow Eye - up to Month 12
Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.
干预措施: Placebo IVT (Other)
Continued - Fellow Eye - up to Month 24
Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.
干预措施: Placebo IVT (Other)
结局指标
主要结局
Change from baseline in Best-Corrected Visual Acuity (BCVA)
时间窗: 12 Months
Change from baseline in BCVA based on the Freiburg Acuity and Contrast Test (FrACT) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
次要结局
- Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)
- Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF(Month 12)
- Change from baseline in retinal sensitivity as measured by dark-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)
- Eye-specific Patient Global Impression of Change (PGI-C) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)
- Change from baseline in retinal sensitivity as measured by light-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)
- Response in BCVA (FrACT), defined as an improvement of at least 0.2 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement.(Month 12)
- Response in BCVA (FrACT), defined as an improvement of at least 0.3 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement.(Month 12)
- Response in Low Luminance Visual Acuity (LLVA) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.(Month 12)
- Response in Full-Field Stimulus Test (FST) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.(Month 12)
- Response in Patient Global Impression of Change (PGI-C) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.(Month 12)
- Response in Contrast Sensitivity (CS) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement.(Month 12)
- Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age(Month 12)
- Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age(Month 12)
- Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age(Month 12)
- Change from baseline in eye-specific Patient Global Impression of Severity (PGI-S) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)
- Response defined as a clinically relevant improvement according to a multimodal assessment in TEs compared to the corresponding response in PCEs at 12 months(Month 12)
- Change from baseline in Best-Corrected Visual Acuity (BCVA) based on the ETDRS and/or the BRVT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)
- Change from baseline in Low Luminance Visual Acuity (LLVA) based on the ETDRS between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)(Month 12)