An Open-Label, Fixed-Sequence, Ascending-Dose, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Intravenous Infusions of ATB200 Co-Administered With Oral AT2221 in Adult Subjects With Pompe Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 19
- 主要终点
- Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug
研究概览
简要总结
This is an international, multi-center, open-label study designed to evaluate if the co-administration of investigational new drugs ATB200 and AT2221 is safe in adults with Pompe disease.
详细描述
This is an open-label, fixed-sequence, ascending-dose, first-in-human study to evaluate the effect of a highly targeted rhGAA (ATB200) co-administered with an enzyme stabilizer (AT2221).
The study aims to evaluate safety, tolerability, pharmacokinetics (PK), efficacy, pharmacodynamics (PD), and immunogenicity of ATB200 co-administered with AT2221.
Stage 1: evaluation of safety, tolerability, and PK following sequential single ascending doses of intravenously infused ATB200
Stage 2: evaluation of safety, tolerability, and PK following single- and multiple-ascending dose combinations of ATB200 and AT2221
Stage 3: evaluation of long term safety, tolerability, and efficacy following 24 month treatment of ATB200 co-administered with AT2221
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Received treatment with prohibited medications within 30 days of Baseline Visit
- •Subject, if female, was pregnant or breastfeeding at screening
- •Subject, whether male or female, planned to conceive a child during the study
- •Had a medical or any other extenuating condition or circumstance that may, in opinion of investigator, pose an undue safety risk to the subject or compromise his/her ability to comply with protocol requirements
- •Had a history of allergy or sensitivity to alglucosidase alfa, miglustat or other iminosugars (Cohorts 1, 2, and 4)
- •Required invasive ventilatory support, or used noninvasive ventilatory support ≥ 6 hours a day while awake (Cohorts 1, 3, and 4)
- •Had active systemic autoimmune disease such as lupus, scleroderma, or rheumatoid arthritis; subjects with autoimmune disease must have been discussed with the Amicus Medical Monitor
- •Had active bronchial asthma; subjects with bronchial asthma must have been discussed with the Amicus Medical Monitor
研究组 & 干预措施
ATB200
Sequential single ascending doses of intravenously infused ATB200 for 3 dosing periods
干预措施: ATB200 (Drug)
ATB200 + AT2221
ATB200 co-administered with AT2221 (Miglustat)
干预措施: ATB200 (Drug)
ATB200 + AT2221
ATB200 co-administered with AT2221 (Miglustat)
干预措施: AT2221 (Drug)
结局指标
主要结局
Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events (AEs) Leading to Discontinuation of Study Drug
时间窗: Stage 3 (2 year treatment) and Stage 4 (Extension) combined, (mean = 71 months on treatment)
Number of subjects with TEAE, TESAE, and AE leading to discontinuation during the 2 year treatment period and extension (Stage 3 and 4 combined)
Plasma Human Acid α-glucosidase (GAA) Activity Levels as Measured by Maximum Observed Plasma Concentration (Cmax).
时间窗: 18 Weeks
Plasma GAA levels (Cmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Plasma GAA Activity Levels as Measured by Time to Reach the Maximum Observed Plasma Concentration (Tmax).
时间窗: 18 Weeks
Plasma GAA levels (Tmax) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
Plasma GAA Activity Levels as Measured by Area Under the Plasma Drug Concentration-time Curve (AUC).
时间窗: 18 Weeks
Plasma GAA levels (AUC) measured in Cohorts 1 and 3 following 1st and 3rd doses of cipaglucosidase alfa + miglustat
次要结局
- Change From Baseline in 6-minute Walk Distance (6MWD)(Baseline, Month 60)
- Change From Baseline in Pulmonary Function Tests(Baseline, Month 60)
- Change From Baseline in Muscle Strength Tests(Baseline, Month 60)
- Change From Baseline in Fatigue Severity Score (FSS)(Baseline, Month 60)
- Change From Baseline in Overall Physical Wellbeing (Subject's Global Impression of Change [SGIC], Question1)(Baseline, Month 60)
- Change From Baseline in Overall Physical Wellbeing (Physician's Global Impression of Change [PGIC])(Baseline, Month 60)