A Phase 1/2a, Open-Label, Multi-Center, Dose-Escalation Trial to Assess Safety, Tolerability, and Efficacy of a Single Dose of CAP-002 Gene Therapy Administered to Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 8
- 主要终点
- Primary Safety
研究概览
简要总结
The goal of this clinical trial is to learn about the safety of CAP-002 gene therapy in children with Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy. It will also provide information about whether CAP-002 demonstrates efficacy in treating children with STXBP1 with and without seizures.
Participants will have a single infusion of CAP-002, visit the clinic regularly for 2 years for checkups and tests and have seizures recorded in a diary by their caregiver.
详细描述
This is a Phase 1/2a, FIH, open-label, multi-center, dose-escalation trial to assess the safety, tolerability, and efficacy of a single intravenous (IV) dose of CAP-002 administered to participants with syntaxin-binding protein#1 (STXBP1) encephalopathy ages ≥18 months to <8 years of age.
Approximately 12 participants will be dosed in this trial. Phase 1 is a dose escalation phase that will dose approximately 6 participants divided into 2 cohorts (Cohort 1 and Cohort 2) while Phase 2a will have 1 dose cohort and dose approximately 6 participants. Participants in Phase 1 will be dosed sequentially in each cohort. Phase 2a will allow participants to be dosed concurrently if safety and tolerability data from Phase 1 are deemed acceptable.
Participants will receive a single intravenous infusion of CAP-002 and will then be followed for 2 years with safety measures, assessments to measure changes from Baseline in development, language, cognition, motor skills and behavior, a seizure diary and structured caregiver interviews.
Upon completion of the study or at the participant's final visit they will be invited to participate in a 3 year safety follow up study.
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
- 18 Months 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, ≥18 months to <8 years of age;
- •Has diagnosis of developmental encephalopathy due to an STXBP1 mutation with confirmation of a pathogenic or likely pathogenic STXBP1 gene mutation.
- •Has a legally authorized representative (LAR) willing and able to complete the informed consent process, willing to comply with trial procedures, and able to travel for repeat visits.
- •Is stable on any medication regimens (if being administered to control the signs and symptoms of underlying disease) for at least 6 weeks prior to trial entry and expected to be stable for at least 12 weeks post-CAP-002 administration.
排除标准
- •History of prior gene therapy;
- •Treatment with antisense oligonucleotide therapy within 6 months;
- •Presence of a confirmed mutation in a gene other than STXBP1 that is known to contribute to a neurodevelopmental disability or epilepsy;
- •Has presence of a significant non-STXBP1-related central nervous impairment/behavioral disturbance that would confound the scientific rigor or interpretation of results of the trial;
- •History of prematurity (defined as gestational age <35 weeks), history of low birth weight (<2.5 kg) and/or intra-uterine growth restriction, significant interventricular hemorrhage, structural brain deficit, or congenital heart disease;
- •Known contraindication to immunosuppression or other protocol-defined medications, including but not limited to corticosteroids or PPIs;
- •Clinically significant abnormalities in safety lab tests, vital signs;
- •Other illnesses or medications that may affect the interpretation of the study results;
- •Positive anti-capsid antibody test result.
研究组 & 干预措施
Dose Level 2
Participants will receive a single dose of STXBP1, administered IV
干预措施: gene therapy (Drug)
Dose Level 1
Participants will receive a single dose of STXBP1, administered IV
干预措施: gene therapy (Drug)
结局指标
主要结局
Primary Safety
时间窗: 2 years
Incidence of Adverse Events and Serious Adverse Events assessed through Clinical safety laboratory tests (hematology, chemistry, liver function, and urinalysis), ECG, vital sign measurements, and Physical Examinations
次要结局
- Bayley Scales of Infant and Toddler Development- Fourth Edition(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Gross Motor Function Measure(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Peabody Developmental Motor Scales-Third Edition(Baseline, Month 6, Month 12, Month 18 and Month 24)
- STXBP1-Clinical Severity Assessment-Clinician(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Vineland Adaptive Behavior Scales | Third Edition(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Observer-Reported Communication Ability(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Sensory Profile-2(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Quality of Life Inventory-Disability(Baseline, Week 6, Month 6, Month 12, Month 18 and Month 24)
- STXBP1-Clinical Severity Assessment-Caregiver(Baseline, Week 4, Week 8, Week 12, Month 4, Month 6, Month 12, Month 18 and Month 24)
- Aberrant Behavior Checklist(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Child Behavior Checklist(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Child's Sleep Habits(Baseline, Month 6, Month 12, Month 18 and Month 24)
- Seizure frequency(Baseline and daily though Month 24)