An Open-label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of 12 Month Treatment With Migalastat in Pediatric Subjects (Aged 2 to < 12 Years) With Fabry Disease and Amenable GLA Variants
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 8
- 试验地点
- 19
- 主要终点
- Safety: Incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug
研究概览
简要总结
An open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric subjects 2 to < 12 years of age with Fabry disease and with amenable GLA variants.
详细描述
This is a Phase 3b, 2-stage, open-label, uncontrolled, multicenter study to evaluate the safety, PK, PD, and efficacy of 12 months of migalastat treatment in pediatric subjects 2 to < 12 years of age with Fabry disease and with amenable GLA variants. Subjects must be either naïve to enzyme replacement therapy (ERT) or have stopped ERT at least 14 days before Baseline visit.
The study will consist of 2 treatment stages followed by an open-label extension (OLE). Stage 1 will be a treatment period of approximately 3 months (12 weeks); Stage 2 will be a treatment period of 9 months. There will be no break in treatment between Stages 1 and 2. There will be a 30-day (untreated) safety follow-up period for subjects who discontinue treatment at any time.
Subjects will be randomly assigned 1:1:1 to 1 of 3 PK sampling groups using interactive response technology (IRT). Four blood samples for the determination of migalastat concentrations in plasma will be collected in one 24-hour period between Day 15 and Day 30 and at Month 6, and 1 PK (trough) sample will be collected at Month 6 and again at Month 12.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects, diagnosed with Fabry disease who are between ages 2 and < 12 years at randomization (subjects aged 11 years must have birthdays > 30 days after randomization)
- •Subject's parent or legally authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable.
- •Subject has a GLA variant documented in his/her medical record that is amenable to migalastat prior to Visit
- •Subject has not received ERT (eg, Replagal® [agalsidase alfa] or Fabrazyme® [agalsidase beta]) for at least 14 days prior to Baseline visit.
- •Subject has at least 1 documented complication (ie, historical or current laboratory abnormality or sign/symptom) of Fabry disease
- •If of reproductive potential, both male and female subjects agree to use a medically accepted method of contraception throughout the duration of the study and for up to 30 days after their last dose of migalastat.
排除标准
- •Has moderate or severe renal impairment (eGFR < 60 mL/min/1.73 m2 at Visit 1 [screening]).
- •Has advanced kidney disease requiring dialysis or kidney transplantation.
- •History of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol).
- •Has received any investigational/experimental drug, biologic, or device within 30 days or 5 half-lives of the investigational product (whichever is longer) before Visit 1 (screening).
- •Has received any gene therapy at any time or anticipates starting gene therapy during the study period.
- •Requires treatment with Glyset (miglitol) or Zavesca (miglustat), within 6 months before Visit 1(screening) or throughout the study.
- •Has any intercurrent illness or condition at Visit 1 (screening) or Visit 2 (baseline) that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study.
- •Pregnant or breastfeeding
- •Otherwise unsuitable for the study in the opinion of the investigator
研究组 & 干预措施
Migalastat HCl 20 mg Dispersible Tablets
Migalastat will be administered every other day (QOD). The initial dose will be based on body weight at baseline.
干预措施: Migalastat HCl 20 mg (Drug)
结局指标
主要结局
Safety: Incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug
时间窗: Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Migalastat
时间窗: 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
Pharmacokinetics (PK): Minimum Observed Plasma Concentration (Cmin) of Migalastat
时间窗: 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve Over The Dosing Interval (AUCtau) of Migalastat
时间窗: 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
次要结局
- Efficacy: Change in urine protein and albumin/microalbumin levels from baseline(Baseline to Months 3, 6, and 12/ET)
- Pharmacodynamic: Change in plasma levels of lyso-Gb3 and its analogs from baseline(Baseline to Months 3, 6, and 12/ET)
- Efficacy: Change in eGFR from baseline(Baseline to Months 1, 3, 6, and 12/ET)
- Efficacy: Change in Left Ventricular Mass Index (LVMi) from baseline(Baseline to Month 12/ET)
- Efficacy: Change in FABPRO-GI And Pain Scores from baseline(Baseline to Month 12/ET)
- Efficacy: Mean Patient's Global Impression Of Change (PGI-C) values(Months 3, 6, and 12/ET)
- Efficacy: Change in PedsQL scores from baseline(Baseline to Month 12/ET)
- Efficacy: Change in EQ-5D-Y scores from baseline (subjects aged ≥4 years)(Baseline to Month 12/ET)
- Efficacy: Change in FPHPQ scores from baseline (subjects aged ≥4 years)(Baseline to Month 12/ET)