An Open-label, Multicenter, Multinational Extension Study of the Long-term Safety, Pharmacodynamics, and Exploratory Efficacy of GZ/SAR402671 in 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
- 8
- 试验地点
- 7
- 主要终点
- Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
研究概览
简要总结
Primary Objective:
To assess the long-term safety of GZ/SAR402671 in adult male participants with Fabry disease who previously completed study ACT13739 (NCT02489344).
Secondary Objective:
To assess the long-term effect of GZ/SAR402671 on pharmacodynamic and exploratory efficacy endpoints in adult male participants with Fabry disease who previously completed study ACT13739.
详细描述
The total duration of this extension study (LTS14116) was up to 31 months (30 months of treatment and one month post-treatment follow-up).
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 —（Adult, Older 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
Participants received GZ/SAR402671 15 milligrams (mg) once daily orally for 30 months in this extension study (LTS14116).
干预措施: GZ/SAR402671 (Drug)
结局指标
主要结局
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant abnormalities: * Alanine Aminotransferase (ALT): \>3 ULN; \>5 ULN; \>10 ULN and \>20 ULN * Aspartate aminotransferase (AST): \>3 ULN; \>5 ULN; \>10 ULN and \>20 ULN * Alkaline phosphatase: \>1.5 ULN * Bilirubin: \>1.5 ULN; \>2 ULN.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Urinalysis
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria with potentially clinically significant urine abnormalities: pH: \<= 4.6; pH: \>= 8.0
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant abnormalities: * Creatinine: \>=150 micromoles per liter (mcmol/L) (Adults); \>=30% change from baseline; \>= 100% change from baseline * Blood urea nitrogen: \>=17 mmol/L * Urate: \<120 mcmol/L; \>408 mcmol/L For this analysis, baseline was defined as initial ACT13739 study baseline.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE) without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened during TEAE period (period from the first administration of study drug in ACT13739 through the last administration of the study drug in the combined ACT13739/LTS14116 treatment period plus 1 month or end of study participation for participant, whichever occurred first). For this analysis, baseline was defined as initial ACT13739 study baseline.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant abnormalities: * Hemoglobin: less than or equal to (\<=) 115 grams per liter (g/L); greater than or equal to (\>=)185 g/L; decreased from baseline (DFB) \>=20 g/L * Hematocrit: \<=0.37 volume/volume (v/v); \>=0.55 v/v * Erythrocytes: \>=6 Tera/L * Platelets: lesser than (\<) 100 Giga/L; \>=700 Giga/L * Leukocytes: \<3.0 Giga/L (Non-Black \[NB\]) or \<2.0 Giga/L (Black \[B\]); \>=16.0 Giga/L * Neutrophils: \<1.5 Giga/L (NB) or \<1.0 Giga/L (B); * Lymphocytes: greater than (\>) 4.0 Giga/L * Monocytes: \>0.7 Giga/L * Basophils: \>0.1 Giga/L * Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L) For this analysis, baseline was defined as initial ACT13739 study baseline.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant abnormalities: * Glucose: \<=3.9 mmol/L and \< lower limits of normal (LLN); \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]) * Lipase: \>= 3 ULN * C Reactive Protein (CRP): \> 2 ULN or \> 10 milligrams (mg)/L (if ULN not provided).
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant ECG abnormalities: * ECG mean HR: \<30 bpm; \<30 bpm and DFB \>=20 bpm; \<40 bpm; \<40 bpm and DFB \>=20 bpm; \<50 bpm; \<50 bpm and DFB \>=20 bpm; \>90 bpm; \<90 bpm and DFB \>=20 bpm; \>100 bpm; \<100 bpm and DFB \>=20 bpm; \>120 bpm; \<120 bpm and DFB \>=20 bpm * PR Interval: \>200 milliseconds (ms); \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB \>=25% * QRS duration: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25% * QTc Bazett (QTcB) interval: \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms, IFB \>60 ms * QTc Fridericia (QTc F): \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms * QT Interval: \>500 ms For this analysis, baseline was defined as initial ACT13739 study baseline.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant abnormalities: * Sodium: \<=129 millimoles (mmol)/L; \>=160 mmol/L * Potassium: \<3 mmol/L; \>=5.5 mmol/L * Chloride: \<80 mmol/L; \>115 mmol/L.
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
时间窗: From baseline of ACT13739 study up to 37 months post-ACT13739 baseline
Criteria for potentially clinically significant vital sign abnormalities: * Systolic blood pressure (SBP) supine: \<=95 millimeters of mercury (mmHg) and DFB \>=20 mmHg; \>=160 mmHg and increase from baseline (IFB) \>=20 mmHg * Diastolic blood pressure (DBP) supine: \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg * Heart rate (HR) supine: \<=50 beats per minute (bpm) and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm * Weight: \>=5% DFB; \>=5% IFB For this analysis, baseline was defined as initial ACT13739 study baseline.
次要结局
- Change From Baseline in Podocyturia Counts (Per Milligram of Creatinine) At Weeks 12, 26, and 156(Baseline of ACT13739 study and Weeks 12, 26, and 156 post-ACT13739 baseline)
- Change From Baseline in Plasma Monosialodihexosylganglioside (GM3) Concentration At Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in Plasma Globotriaosylceramide (GL-3) Concentration at Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Number of Participants in Categories of Response Regarding Eating Less Due to Abdominal Pain/Bloating at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in Plasma Lyso Globotriaosylceramide (Lyso GL-3) Concentration at Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in Plasma Glucosylceramide (GL-1) Concentration At Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in Urine GL-3 Concentration At Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Summary of Shifts From Baseline in Skin GL-3 Score in Superficial Capillary Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score(Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline)
- Summary of Shifts From Baseline in Skin GL-3 Score in Perineurium Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score(Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline)
- Change From Baseline in Mental Component Summary and Physical Component Summary of the Short Form-36 (SF-36) Health Survey at Weeks 26, 52, 104 and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Number of Participants With Abdominal Distension at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in High Sensitivity Cardiac Troponin T At Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Endothelial Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score(Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Number of Days With Abdominal Pain Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Abdominal Distension Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Satisfaction Over Bowel Habits at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Influence of GI Symptoms of Fabry Disease on Life at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Summary of Shifts From Baseline in Skin GL-3 Score in Deep Vessels Smooth Muscle Cells Over Time: Number of Participants in Categories of Shift in GL-3 Score(Baseline of ACT13739 study and Weeks 12, 26, 52, and 156 post-ACT13739 baseline)
- Gastrointestinal (GI) Symptoms: Number of Participants With Abdominal Pain at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Abdominal Pain Severity Score at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Number of Participants in Categories of Brain Magnetic Resonance Imaging (MRI) Results at Baseline and Weeks 26, and 156(Baseline of ACT13739 study and Weeks 26, and 156 post-ACT13739 baseline)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Frequency of Bowel Movements - Most Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Frequency of Bowel Movements - Least Number of Times Bowel Movement Per Day at Baseline and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 2, 4, 8, 12, 18, 26, 52, 104, and 156 post-ACT13739 baseline)
- Gastrointestinal Symptoms: Number of Participants With Stool Consistency Assessment by Bristol Stool Scale Scoring at Baseline and Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in Beck Depression Inventory (BDI) Total Score at Weeks 26, 104, and 156(Baseline of ACT13739 study and Weeks 26, 104, and 156 post-ACT13739 baseline)
- Change From Baseline in Albumin/Creatinine Ratio (ACR) and Protein/Creatinine Ratio (PCR) at Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Number of Participants in Categories of Echocardiogram (ECHO) Results at Baseline and at Weeks 26, 52, 104, and 156(Baseline of ACT13739 study and Weeks 26, 52, 104, and 156 post-ACT13739 baseline)
- Chitotriosidase (Chit1) Plasma Concentration Levels at Weeks 52, 104,156 and 160 (End of Treatment Follow-up)(Weeks 52, 104, 156 and 160 (End of Treatment Follow-up) post-ACT13739 baseline)