A Multi-Center, Open-Label, Randomized Study Evaluating the Safety and Efficacy of Three Dosing Regimens of Replagal Enzyme Replacement Therapy in Adult Patients With Fabry Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 44
- 试验地点
- 22
- 主要终点
- Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)
研究概览
简要总结
The purpose of this study is to compare the safety and effectiveness of various doses of Replagal in patients with cardiomyopathy due to Fabry disease.
详细描述
Fabry disease is an inherited, metabolic disease caused by mutations in the GALA gene. Patients with Fabry disease accumulate a complex glycosphingolipid named globotriaosylceramide (Gb3) in various tissues and organs. All organs are affected in Fabry disease but the majority of the morbidity and mortality are caused by cardiac, renal and neurological dysfunction. Accumulation of Gb3 in the heart causes hypertrophic cardiomyopathy, valvular abnormalities, arrhythmias and infarctions. Replagal has been shown to reduce Gb3 from key tissues and organs, and stabilize renal function in patients with Fabry disease. Evidence suggests that Replagal reduces left ventricular mass (LVM) and improves midwall fractional shortening (MFS) of the heart. Left ventricular hypertrophy is a major cause of morbidity and mortality in patients with Fabry disease.
This is a study of the safety and effectiveness of 3 dosing regimens of Replagal in adult patients with left ventricular hypertrophy due to Fabry disease.
The primary objective of the study is to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on the reduction of left ventricular mass as measured by echocardiography.
The secondary objectives of this study are to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on each of the following: exercise tolerance; improvement in disease-specific quality of life in heart failure patients; improvement of heart failure symptoms; magnitude of reduction in Gb3; rate of decline in renal function and improvement in the severity of proteinuria/albuminuria; and safety.
An alternative treatment regimen of 0.4 mg/kg Replagal IV weekly will also be explored but without formal comparison to the 0.2 mg/kg regimens. The investigation of the safety and efficacy of the 0.4 mg/kg IV weekly regimen is a secondary objective of this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>18 years-old;
- •Male:Fabry disease confirmed by deficiency of alfa galactosidase A activity OR Female:Fabry disease confirmed by a mutation of the alfa galactosidase A gene;
- •ERT-naïve;
- •LVM/h > 50g/m2.7 for males and >47 g/m2.7 for females;
- •Negative pregnancy test at enrollment and contraception use required throughout study for female patients;
- •Signed informed consent;
排除标准
- •Class IV heart failure;
- •Clinically significant hypertension;
- •Hemodynamically significant valvular stenosis or regurgitation;
- •Morbid obesity;
- •Known autosomal dominant sarcoplasmic contractile protein gene mutation;
- •Treatment with any investigational drug or device within the 30 days;
- •Unable to comply with the protocol as determined by the Investigator;
- •Positive for hepatitis B, hepatitis C or HIV
结局指标
主要结局
Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)
时间窗: Baseline, Month 12 (Week 53)
Left ventricular mass (LVM) was measured through echocardiography.
次要结局
- Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score(Baseline, Month 12 (Week 53))
- Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)(Baseline, Month 12 (Week 53))
- Change From Baseline to Month 12 in New York Heart Association (NYHA) Functional Class(Baseline, Month 12 (Week 53))
- Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)(Baseline, Month 12 (Week 53))
- Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio(Baseline, Month 12 (Week 53))
- Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise(Baseline, Month 12 (Week 53))
- Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)(Baseline, Month 12 (Week 53))
- Safety Evaluation(56 Weeks)