NCT04732429终止2 期
A Phase 2 Open-label, Dose Escalation Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia Followed by a Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study and an Open-label, Long-term Extension Study
HemoShear Therapeutics16 个研究点 分布在 3 个国家目标入组 26 人开始时间: 2021年3月15日最近更新:
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 26
- 试验地点
- 16
- 主要终点
- Change in plasma 2-methylcitric acid (MCA) levels
研究概览
简要总结
This is an interventional study to assess the safety, PK, and efficacy of HST5040 in 12 subjects - 6 with Methylmalonic Acidemia (MMA) and 6 with Propionic Acidemia (PA). The study consists of 3 parts:
- Part A: Open-label, within-subject, dose escalation study in PA and MMA subjects ≥ 2 years old to identify a safe and pharmacologically active (optimal) dose of HST5040 for use in Part B. Subjects will continue in a Part A open-label extension until all subjects complete Part A and the optimal dose of HST5040 is identified for use in Part B.
- Part B: 6-month, randomized, double-blind, placebo-controlled, 2-period crossover in the same subjects from Part A to evaluate safety and efficacy of the optimal dose of HST5040 in addition to standard of care (SoC).
- Part C: open-label long-term extension study in PA and MMA subjects ≥ 2 years old (N = approximately 12, 6 each) to evaluate the long-term safety and efficacy of the optimal dose of HST5040.
This study will determine whether HST5040 can improve levels of disease-associated toxins that accumulate in patients with PA and MMA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of symptomatic PA or MMA (Mutase)
- •Ages ≥ 2 years old.
- •History of Inadequate metabolic control while receiving standard of care (SoC).
- •Plasma MCA concentration > 3x upper limit of normal of the reference range at screening.
- •Stable supplementation dose of carnitine for at least 1 week prior to the entry in the study.
排除标准
- •Moderate-to-severely impaired cardiac function with LVEF < 45% by ECHO.
- •Clinically significant arrhythmia by Holter monitor.
- •QTcF > 450 msec
- •Moderate to severe chronic kidney disease with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m
- •Exposure to any investigational therapy, apart for a COVID-19 vaccine, within the past 6 months prior to study entry.
- •Exposure to gene therapy for PA or MMA at any time prior to study entry.
- •History of organ transplantation (Part A and B only)
- •History of severe allergic or anaphylactic reactions to any of the components of HST5040.
研究组 & 干预措施
Active Drug
Experimental
Part B is the 6-month, randomized, double-blind (Subject/Investigator/Sponsor), placebo-controlled, 2-period crossover study consisting of 2 intervention periods of 12 weeks each to evaluate the safety and efficacy of the optimal dose of HST5040 in PA and MMA subjects ≥ 2 years old (N = minimum 12) in addition to SoC determined in Part A (within-subject dose escalation).
干预措施: HST5040 (Drug)
Placebo
Experimental
Placebo in addition to standard of care.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in plasma 2-methylcitric acid (MCA) levels
时间窗: 6 months
nmol/mL
次要结局
- Change in plasma propionyl-carnitine (3)(6 months)
- Change in C3 to acetyl-carnitine ratio (C3:C2)(6 months)
- Change in 3-OH propionate(6 months)
- Pharmacokinetics parameters - Cmax(6 months)
- Pharmacokinetics parameters - AUC(6 months)
- Change in Methylmalonic acid (in MMA subjects)(6 months)
- Anion Gap(6 months)
- Oral Intake(6 months)
- Acute Metabolic Decompensations(6 months)
- Pharmacokinetics parameters - Tmax(6 months)
- MetabQoL 1.0 - Health Related Quality of Life (HRQOL)(6 months)
- PedsQL 1.0 Family Impact Score - Health Related Quality of Life (HRQOL)(6 months)
- Change in NH3(6 months)
研究者
研究点 (16)
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