A Phase 1/2 Open-label Clinical Study of hLB-001 Gene Therapy in Pediatric Patients With Methylmalonic Acidemia Characterized by MMUT Mutations
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 5
- 主要终点
- Number of Participants With Infusional Toxicities
研究概览
简要总结
The SUNRISE trial is a first-in-human (FIH), open-label, Phase 1/2 clinical trial designed to assess the safety, tolerability and preliminary efficacy of a single intravenous infusion of hLB-001 in pediatric patients with MMA characterized by methylmalonyl-CoA mutase gene (MMUT) mutations. hLB-001 is a liver-targeted, recombinant engineered adeno-associated viral (rAAV) vector utilizing the LK03 capsid (rAAV-LK03), designed to non-disruptively integrate the human methylmalonyl-CoA mutase gene at the albumin locus.
The trial is expected to enroll pediatric patients with ages ranging from 6 months to 12 years, initially starting with 3 to 12 year-old patients and then adding patients aged 6 months to 2 years.
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
- 6 Months 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At the time of dosing, participants must be 6 months to 12 years of age
- •Males and females with diagnosis of severe MMA meeting all the following;
- •Isolated MMA with genetically confirmed, pathogenic mutations in the MMUT gene
- •Screening serum/plasma methylmalonic acid level of >100 µmol/L
- •One or more of the following considered by the PI to be MMA-related: (i) An unscheduled ER visit, hospitalization or requirement for sick day diet in the year prior to screening visit (ii) Developmental delay, movement disorder, optic neuropathy or feeding disorder with tube feeding requirement
- •Medically stable for the 2 months prior to the start of screening
排除标准
- •Participants with organic acidemias other than isolated MMA, or with any other causes of hyperammonemia
- •Having received MMA-targeted gene therapy or nucleic acid therapy
- •Participants on insulin or high dose hydroxocobalamin (> 1 mg/day OHB12 parenteral)
- •Kidney or liver transplant, including hepatocyte cell therapy
- •Estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 based on age appropriate equations, or ongoing dialysis for renal disease
- •Participant tests positive for anti-rAAV-LK03-neutralizing antibodies
结局指标
主要结局
Number of Participants With Infusional Toxicities
时间窗: Baseline up to Week 52
An infusional toxicity was a hLB-001-related AE that limits, delays, or requires medical intervention during administration. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug up to Week 52
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAE was an AE that was not present prior to administration of hLB-001, or an event already present that worsened in either severity or frequency following hLB-001administration. A summary of serious adverse events (SAEs) and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
次要结局
- Percent Change From Baseline in Propionate Oxidation Rate at Week 52(Baseline, Week 52)
- Change From Baseline in Serum Albumin-2A Level at Week 52(Baseline, Week 52)
- Change From Baseline in Serum Fibroblast Growth Factor 21 (FGF21) Level at Week 52(Baseline, Week 52)
- Change From Baseline in Serum Methylmalonic Acid Level at Week 52(Baseline, Week 52)
- Change From Baseline in Serum Methylcitrate Level at Week 52(Baseline, Week 52)