A Phase 1/2 Study of Antisense Oligonucleotide Therapy for Treatment of Ataxia-Telangiectasia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Neurological function as measured by the AT-NEST scale
研究概览
简要总结
This project aims to evaluate the safety and efficacy of precision genetic therapy for patients with Ataxia-telangiectasia (A-T), a rare neurodegenerative disease caused by mutations in the ATM gene. The investigators will conduct a clinical trial to study the safety and efficacy of intrathecal administration of atipeksen, a targeted genetic therapy that restores ATM gene function in A-T individuals bearing the recurrent ATM c.7865C>T variant. The aim of this study is to delay or forestall progression of neurologic symptoms in A-T and improving quality of life. Success will provide an empirical foundation for advancing additional precision genetic therapies for A-T and other neurodegenerative conditions.
详细描述
The goal of this protocol is to study the safety and efficacy of the investigational drug atipeksen, a mutation-specific antisense oligonucleotide (ASO), in individuals with ataxia telangiectasia (A-T). The first objective is to evaluate the safety of therapy with atipeksen, a 22-nucleotide oligonucleotide designed to ameliorate the effects of mis-splicing caused by a mutation in the ATM gene(NM_000051.3), c.7865C>T (p.Ala2622Val), when administered via intrathecal injection. The second objective is to determine if administration of intrathecal atipeksen can reduce or stabilize neurological decline using clinical and physiological biomarkers. The primary endpoint will be serial clinical neurologic assessments using the Ataxia-Telangiectasia Neurological Examination Toolkit (A-T NEST) and a structured version of the Ataxia-Telangiectasia Clinical Global Impression of Change (A-T CGI). Secondary endpoints will include videotaped clinical neurological examinations, movement pattern analyses using wearable actigraphy, and standard scales administered by PT, OT, and neuropsychology. Exploratory endpoints include serial brain imaging with volumetric analyses, neurofilament light chain, alpha-fetoprotein, and growth parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Who can take part:
- •People with classic A-T confirmed by genetic testing
- •Must have a specific ATM gene change (c.7865C>T)
- •Must also have another ATM change that causes A-T
- •Who cannot take part:
- •People with health problems that make lumbar puncture unsafe:
- •Blood clotting or bleeding problems
- •Brain conditions raising pressure inside the head
- •Serious heart or breathing problems
- •Infection near the lower back
- •Other things doctors will check:
- •Overall health and stability
- •Any medicines that might cause problems
- •Past difficulties with lumbar punctures
- •Any other safety concerns
研究组 & 干预措施
Phase 1/2 Study of Antisense Oligonucleotide Therapy for Treatment of Ataxia - Telangiectasia
Individuals with genetically confirmed, classic ataxia telangiectasia with at least one copy of the ASO-amenable ATM variant NM_000051.3:c.7865C>T;p.Ala2622Val, will receive the ASO at the same dose.
干预措施: Antisense oligonucleotide targeting the ATM gene (Drug)
结局指标
主要结局
Neurological function as measured by the AT-NEST scale
时间窗: At Baseline and every 12 weeks up to ten years
The Ataxia-Telangiectasia Neurological Examination Toolkit (AT-NEST) is a test designed specifically for people with Ataxia-Telangiectasia (A-T). It helps doctors and researchers understand how the brain and nerves are working. The test looks at six main areas: * Communication * Eye movements Ataxia (problems with balance and coordination) * Movement disorders * Muscle strength (Power) * Nerve function (Neuropathy) These six areas make up the "pure neuro" score, which ranges from 0 (lowest) to 100 (highest). The test also includes growth and nutrition. When these are added to the six main areas, a total "neuro-related" score is calculated, with a maximum of 114. Higher scores mean better overall performance.This test is not painful and is carried out by trained specialists who will guide you through each step.
Ataxia-Telangiectasia Structured Clinical Global Impression of Change (A-T CGI)
时间窗: At Baseline and every 12 weeks up to ten years
The Ataxia-Telangiectasia Clinical Global Impression of Change (AT-CGI) is a tool used to track how A-T progresses over time. It looks at five main areas of the disease: Ataxia (balance and coordination problems) Dysarthria (difficulty speaking) Repetitive movements / Dysmetria (trouble controlling movements) Movement disorders Eye movements Each area is scored from 0 to 4, for a total of 20 points. Higher scores mean more severe symptoms, while lower scores indicate better function.
次要结局
- Performance and goal satisfaction as measured by the Canadian Occupational Performance Measure (COPM)(Baseline and every 6 months up to 10 years)
- Performance in activities of daily living as measured by the Pediatric Evaluation of Disability Inventory Computer Adaptive Test(Baseline and every 6 months up to 10 years)
- Visual-motor function as measured by the Beery-Buktenica Developmental Test of Visual Motor Integration(Baseline and every 6 months up to 10 years)
- Neurodevelopmental function, as measured by the Leiter International Performance, third edition(Baseline and yearly up to 10 years)
- Neurodevelopmental function, as measured Wechsler Intelligence Scale for Children, fifth edition(Baseline and yearly up to 10 years)
- Neurodevelopmental function, as measured by the Vineland Adaptive Behavior Scale(Baseline and yearly up to 10 years)
- Motor performance through digital wearable actigraphs(Baseline and every 12 weeks up to 10 years)
- Motor performance as measured by the Bruininks-Oseretsky Test of Motor Proficiency 2nd edition(Baseline and every 6 months up to 10 years)
研究者
Timothy Yu
Physician, Department of Genetics and Genomics, Boston Children's Hospital, Associate Professor, Harvard Medical School Associate Member, Broad Institute
Boston Children's Hospital