A Phase 1/2 Open-Label Study of the Safety and Clinical Activity of Gene Therapy for Canavan Disease Through Administration of an Adeno-Associated Virus (AAV) Serotype 9-Based Recombinant Vector Encoding the Human ASPA Gene
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 26
- 试验地点
- 5
- 主要终点
- Number of Participants with Adverse Events (AEs)
研究概览
简要总结
The main objective of this trial is to evaluate the safety, tolerability, and pharmacodynamic activity of BBP-812, an investigational AAV9-based gene therapy, in pediatric participants with Canavan disease.
详细描述
Canavan disease is an ultra-rare, profoundly disabling and fatal disease with no approved therapy. The Sponsor is developing BBP-812, an investigational gene therapy product for systemic delivery in participants with Canavan disease. BBP-812 is a recombinant adeno-associated virus serotype 9 (rAAV9) vector engineered to deliver the aspartoacylase (ASPA) transgene under control of a ubiquitous promoter to restore ASPA expression in both neuronal and non-neuronal cell types.
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
- — 至 30 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Maximum age for inclusion is 30 months.
- •Participant has stable health in the opinion of the investigator and as confirmed by medical history and laboratory studies with no acute or chronic hematologic, renal, liver, immunologic, or neurologic disease (other than Canavan disease).
- •Participant has biochemical, genetic, and clinical diagnosis of Canavan disease:
- •Elevated urinary NAA and
- •Biallelic mutation of the ASPA gene determined at Screening or documented in the participant's medical history.
- •Active clinical signs of Canavan disease
- •Participant is up to date on all immunizations per local guidelines
排除标准
- •Tests positive for total anti-AAV9 antibodies determined by enzyme-linked immunosorbent assay (ELISA).
- •Received prior gene therapy or other therapy (including vaccines) involving AAV.
- •Participant is receiving high-dose therapy with immunosuppressants.
- •Participant has significantly progressed Canavan disease characterized as:
- •Presence of continuous/constant decerebrate or decorticate posturing,
- •Recurrent status epilepticus, or
- •Recalcitrant seizures that do not respond while on 3 or more anti-epileptic medications
研究组 & 干预措施
Dose-Finding Phase: BBP-812 Dose Level 1 (Cohort 1)
Participants will receive a single intravenous (IV) infusion of low-dose BBP-812 on Day 0 in the dose-finding phase of the study.
干预措施: AAV9 BBP-812 (Biological)
Dose-Finding Phase: BBP-812 Dose Level 2 (Cohort 2)
Participants will receive a single IV infusion of high-dose BBP-812 on Day 0 in the dose-finding phase of the study.
干预措施: AAV9 BBP-812 (Biological)
Enrollment Expansion Phase: BBP-812
Participants will receive a single IV infusion of BBP-812 at the selected dose from the dose-finding phase on Day 0 in expansion phase of the study.
干预措施: AAV9 BBP-812 (Biological)
结局指标
主要结局
Number of Participants with Adverse Events (AEs)
时间窗: Baseline up to Week 52
Change from Baseline to 12 Months Post-Infusion in Urine N-acetylaspartate (NAA) Levels
时间窗: Baseline, Month 12
Change from Baseline to 12 Months Post-Infusion in Central Nervous System (CNS) NAA, as Measured by Magnetic Resonance Spectroscopy (MRS)
时间窗: Baseline, Month 12
次要结局
- Change from Baseline to Week 52 in Gross Motor Assessment, Gross Motor Function Measure-88(Baseline, Week 52)
- Change from Baseline to Week 52 in Cognitive Assessment, Bayley-4(Baseline, Week 52)
- Change from Baseline to Week 52 in Adaptive Function, Vineland-3(Baseline, Week 52)
- Change from Baseline to Week 52 in Fine Motor Assessment, Bayley-4(Baseline, Week 52)
- Change from Baseline to Week 52 in Communication Assessment, Bayley-4(Baseline, Week 52)