A Phase 2 Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Exploratory Efficacy of GZ/SAR402671 in Enzyme Replacement Therapy (ERT) Treatment-naïve Adult Male Patients Diagnosed With Fabry Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 8
- 主要终点
- Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26
研究概览
简要总结
Primary Objective:
To assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and exploratory efficacy of GZ/SAR402671 in enzyme replacement therapy treatment-naïve adult male participants diagnosed with Fabry disease.
详细描述
The total duration of study per participant was 7 to 8 months for participants who entered a planned extension study and approximately 13 to 14 months for participants who did not enter a planned extension study. A 2-year extension study was planned for eligible participants.
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
- 18 Years 至 49 Years（Adult）
- 性别
- Male
- 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
GZ/SAR402671
GZ/SAR402671 15 milligram (mg) once daily orally for 26 weeks.
干预措施: GZ/SAR402671 (Drug)
结局指标
主要结局
Change From Baseline at Week 26 in Skin Globotriaosylceramide (GL-3) Score in Superficial Skin Capillary Endothelium: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26
时间窗: Baseline, Week 26
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Data were summarized and reported in terms of number of participants with shift from Baseline GL-3 score to Week 26 GL-3 score. Any shift category of Baseline score/Week 26 score that was not observed is not reported. Shift to lower score from Baseline to Week 26 indicates less severe condition at Week 26.
Mean Change From Baseline at Week 26 in Skin GL-3 Score in Superficial Skin Capillary Endothelium
时间窗: Baseline, Week 26
Skin biopsies taken at Baseline and Week 26 were analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Three independent pathologists evaluated each biopsy using an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe), where higher score indicated more severe condition. A single score per participant per time point was derived by taking the score rated by a majority of the pathologists; if a majority score could not be derived, the median score was used. Change from Baseline in GL-3 score was obtained by subtracting Baseline value from post-baseline value at Week 26. A negative change from Baseline indicates less severe condition at Week 26.
次要结局
- Change From Baseline in Plasma GL-3 Concentration at Week 26(Baseline, Week 26)
- Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso-GL-3) Concentration at Week 26(Baseline, Week 26)
- Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration at Week 26(Baseline, Week 26)
- Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Endothelial Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26(Baseline, Week 26)
- Change From Baseline at Week 26 in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26(Baseline, Week 26)
- Change From Baseline at Week 26 in Skin GL-3 Score in Perineurium Cells: Number of Participants in Categories of Shift in GL-3 Score From Baseline to Week 26(Baseline, Week 26)
- Change From Baseline in Urine Globotriaosylceramide (GL-3) Concentration at Week 26(Baseline, Week 26)
- Pharmacokinetics (PK): Maximum Plasma Drug Concentration (Cmax) of GZ/SAR402671(Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From Baseline up to 212 days)
- PK: Plasma Trough Concentration (Ctrough) of GZ/SAR402671(Predose on Days 14, 28, 56, 84, 126, and 182)
- PK: Area Under Plasma Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24) of GZ/SAR402671(Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose))
- PK: Time to Reach Maximum Plasma Drug Concentration (Tmax) of GZ/SAR402671(Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose))
- PK: Terminal Half-life (t1/2z) of GZ/SAR402671(Day 1 (predose and 1, 2, 4, 8, and 24 hours post-dose); Day 182 (predose and 1, 2, 4, 8, and 24 hours post-dose))
- PK: Apparent Total Body Clearance of GZ/SAR402671 at Steady State (CLss/F)(Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182)
- PK: Cumulated Amount of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (Ae0-24)(0-24 hours on Day 182)
- PK: Renal Clearance (CLR) of GZ/SAR402671 From 0 to 24 Hours(0-24 hours on Day 182)
- PK: Apparent Volume of Distribution of GZ/SAR402671 (Vss/F) at Steady State(Predose and 1, 2, 4, 8, and 24 hours post-dose on Day 182)
- PK: Percentage of Dose of GZ/SAR402671 Excreted in Urine From 0 to 24 Hours (fe0-24)(0-24 hours on Day 182)