A Multicenter, Open-label Study of Low Dose Maintenance Treatment of Fabrazyme (Recombinant Human Alpha-Galactosidase A (R-h Alpha-GAL)) Replacement Therapy in Patients With Fabry Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 8
- 主要终点
- Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
研究概览
简要总结
People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. This enzyme helps to break down and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In people with Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because alpha-galactosidase A is not present, or is present in small quantities. The build up of glycolipid levels (also referred to as "globotriaosylceramide" or "GL-3") in these tissues is thought to cause the clinical symptoms that are common to Fabry disease. Symptoms commonly appear during childhood with pain in the hands and feet. This trial is designed to evaluate the efficacy of a lower dose of Fabrazyme in patients who initially received 1.0 mg/kg every 2 weeks of Fabrazyme by investigating if the achieved clearance of glycosphingolipid deposits in the vascular endothelium of the kidney can be maintained at a lower dose.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Have clinical manifestations of Fabry disease
- •All patients have to have a plasma αGAL activity of < 1.5 nmol/hr/mL or a documented leukocyte αGAL activity of < 4 nmol/hr/mg
- •Patient or patient's parent/guardian had to provide written informed consent prior to any study-related procedures being performed
- •Patients had to be male and ≥ 16 years of age
排除标准
- •There is evidence of renal insufficiency, as defined by serum creatinine greater than or equal to 2.2 mg/dL (194.7 μmol/L) AND/OR has an estimated glomerular filtration rate (GFR) of <80 mL/min (using the equation derived from the Modification of Diet in Renal Disease Study (MDRD))
- •Has undergone kidney transplantation or is currently on dialysis
- •Has a clinically significant organic disease or an unstable condition (with the exception of symptoms relating to Fabry disease) that in the opinion of the Investigator would preclude participation in the trial
- •Has participated in a study employing an investigational drug within 30 days of the start of this trial
- •Patients who received prior treatment with enzyme replacement therapy for Fabry disease
- •Patient was unable to comply with the requirements of the protocol
结局指标
主要结局
Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
时间窗: Throughout study; 96 weeks
Kidney biopsies were taken at Baseline, Week 24, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
次要结局
- Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium(Throughout study ; 96 weeks)
- Estimated Glomerular Filtration Rate (eGFR)(Throughout study; 96 weeks)
- Plasma Globotriaosylceramide (GL-3)(Throughout study; 96 weeks)
- Urine Globotriaosylceramide (GL-3)(Throughout study, 96 weeks)