An Open-label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of 12 Month Treatment With Migalastat in Pediatric Subjects (Aged 12 to <18 Years) With Fabry Disease and Amenable GLA Variants
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- PK: Maximum Observed Plasma Concentration (Cmax) Of Migalastat
研究概览
简要总结
This was an open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric participants 12 to <18 years of age with Fabry disease and amenable gene encoding α-galactosidase A (GLA) variants.
详细描述
This was a Phase 3b, 2-stage, open-label, uncontrolled, multicenter study to evaluate the safety, PK, PD, and efficacy of migalastat treatment in pediatric participants 12 to <18 years of age and weighing ≥ 45 kilograms (99 pounds) with Fabry disease and amenable GLA variants. Participants must have been naïve to enzyme replacement therapy (ERT) or have stopped ERT at least 14 days at the time of screening.
Stage 1 was a treatment period of approximately 1 month (4 weeks); Stage 2 was a treatment period of 11 months and a 30-day (untreated) safety follow-up period. There was no break in treatment between Stages 1 and 2. Prior to Stage 1, there was a screening period lasting at least 14 days and up to 30 days (or more, if GLA genotyping was required). Stages 1 and 2 together consisted of a 12-month treatment period, and a 30-day safety follow-up period, for a total of approximately 13 months. Upon study completion, participants had the option to enroll in a long-term extension study conducted under a separate protocol (NCT04049760).
Participants were 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 were collected during Stage 1 study drug administration, and 1 PK (trough) sample was 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
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
migalastat HCl 150 mg
One migalastat 123 milligrams (mg) capsule equivalent to 150 mg migalastat hydrochloride (HCl) (herein referred to as "migalastat") was administered every other day for 12 months.
干预措施: Migalastat HCl 150 mg (Drug)
结局指标
主要结局
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
PK sampling was performed on 1 occasion at steady-state during the first month of the study. Adolescent participants were randomized to 3 sparse PK sampling groups based on optimal sampling theory. Each blood sample could have been taken at any time within the following time point ranges. Time point ranges for all 3 sparse sampling groups are arranged here in chronological order: 1 to 1.25h, 1.5 to 2h, 2.75 to 3.25h, 3.25 to 3.75h, 3.75 to 4.25h, 5 to 5.5h, 5.25 to 5.75h, 6.5 to 7h, 8.25 to 8.75h, 8.75 to 9.25h, and 10.75 to 11.25h post-dose. The combined sampling scheme resulted in rich data over an approximate 12-hour time course for AUC and Cmax estimation. Additional trough samples were taken at Months 6 and 12. These trough samples (48h) assisted in estimating the terminal elimination phase for the AUC. Simulations were conducted to predict steady-state PK profiles and parameters for adolescent age subgroups 12 to \<16 years, 16 to \<18 years, and overall, 12 to \<18 years.
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
PK sampling was performed on 1 occasion at steady-state during the first month of the study. Adolescent participants were randomized to 3 sparse PK sampling groups based on optimal sampling theory. Each blood sample could have been taken at any time within the following time point ranges. Time point ranges for all 3 sparse sampling groups are arranged here in chronological order: 1 to 1.25 hours (h), 1.5 to 2h, 2.75 to 3.25h, 3.25 to 3.75h, 3.75 to 4.25h, 5 to 5.5h, 5.25 to 5.75h, 6.5 to 7h, 8.25 to 8.75h, 8.75 to 9.25h, and 10.75 to 11.25h post-dose. The combined sampling scheme resulted in rich data over an approximate 12-hour time course for AUC estimation. Additional trough samples were taken at Months 6 and 12. These trough samples (48h) assisted in estimating the terminal elimination phase for the AUC. Simulations were conducted to predict steady-state PK profiles and parameters for adolescent age subgroups 12 to \<16 years, 16 to \<18 years, and overall, 12 to \<18 years.
Number Of Participants Who Experienced Treatment-related Treatment-emergent Adverse Events (TEAEs)
时间窗: Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)
TEAEs included adverse events that began on or after the first dose of study drug until 30 days after the last dose. Treatment-related TEAEs were defined as TEAEs that had an investigator-defined relationship to study drug of "Definite," "Probable," or "Possible." A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
次要结局
- Change In eGFR From Baseline To Month 12(Baseline, Month 12 and last observation (up to Month 12))
- Change From Baseline In FPHPQ Score For Pain Intensity(Baseline, Month 12 and last observation (up to Month 12))
- Annualized Rate Of Change From Baseline(Baseline up to Month 12)
- Change From Baseline In Total Urine Protein And Urine Albumin Levels At Month 12(Baseline, Month 12 and last observation (up to Month 12))
- Change From Baseline In Left Ventricular Mass Index (LVMi)(Baseline, Month 12 and last observation (up to Month 12))
- Change In Plasma Levels Of Globotriaosylsphingosine (Lyso-Gb3)(Baseline, Month 12 and last observation (up to Month 12))
- FABPRO-GI And Pain Scores(Month 12 and last observation (up to Month 12))
- Patient's Global Impression Of Change (PGI-C) Scores(Month 12)
- Number Of Participants Who Experienced Sudden Onset Of Pain As Assessed Using The Fabry-Specific Pediatric Health And Pain Questionnaire (FPHPQ)(Month 12)
- Change From Baseline In Pediatric Quality Of Life (PedsQL) At Month 12(Baseline, Month 12)