Alpha-Galactosidase A Replacement Therapy for Fabry Disease

2014-07-23 21:52:36 | BioPortfolio


This study will determine the safety of the drug Replagal or treating patients with Fabry disease, an inherited metabolic disorder. In this disease, an enzyme called Alpha-galactosidase A, which normally breaks down a fatty substance called globotriaosylceramide (Gb3), is missing or does not function properly. The resulting accumulation of Gb3 causes problems with the kidneys, heart, nerves, and blood vessels. Replagal is a genetically engineered form of Alpha-galactosidase A. Previous studies have shown that patients with Fabry disease who had not progressed to end-stage kidney failure tolerated Replagal replacement therapy well. This study will examine the effects of the drug in patients with kidney problems associated with Fabry disease.

Patients with Fabry disease who are on kidney dialysis, or have had a kidney transplant, may be eligible for this study.

During this 6 to 12-month study, participants will receive a 40-minute intravenous (IV) infusion of Replagal every other week, with close monitoring during and after the infusions. Before the first infusion, patients will be evaluated with a medical history, physical and neurological examinations, electrocardiogram (ECG), routine blood and urine tests, kidney test, and measurements of height, weight, and vital signs (blood pressure, pulse, breathing rate, temperature). In addition, they will have pharmacokinetic studies immediately before and following the first infusion of Replagal. For these studies, blood samples of less than a teaspoon each will be drawn to measure the level of Replagal enzyme activity. The samples will be collected at the following time points: immediately before the infusion; 20 minutes into the infusion; at the end of the infusion; after the infusion at 50, 60, and 90 minutes, and 2, 3, 4, and 8 hours.

Safety evaluations will be done once a week for the first month and then once a month for the rest of the study period. These evaluations include a physical examination, measurement of vital signs, electrocardiogram, routine blood and urine tests, and kidney testing.


The objectives of this clinical trial are to study the effects of a range of renal function on the safety and pharmacokinetics of Replagal enzyme replacement therapy in patients with Fabry Disease. Patients with clinical and genetic or biochemical evidence of Fabry Disease will be selected for this clinical trial. Sixty (60) patients will be enrolled in this clinical trial. Enrollment will be stratified based on baseline renal function as per FDA guidelines. This is an open label clinical study. Baseline evaluations will be conducted over an approximately 3 day period. Patients will receive intravenous (IV) infusions of Replagal at a dose of 0.2 mg/kg/dose every 2 weeks. Pharmacokinetic studies will be performed with the first administered dose. The safety evaluations for patients in this study will include vital signs, physical examinations, adverse event (AE) assessments, electrocardiograms (ECG), and a battery of laboratory tests including measurement of anti-Replagal antibodies. An overview of the study appears in Appendix A.

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


Fabry Disease




National Institute of Neurological Disorders and Stroke (NINDS)
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-07-23T21:52:36-0400

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Generation of Fabry cardiomyopathy model for drug screening using induced pluripotent stem cell-derived cardiomyocytes from a female Fabry patient.

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Medical and Biotech [MESH] Definitions

An X-linked inherited metabolic disease caused by a deficiency of lysosomal ALPHA-GALACTOSIDASE A. It is characterized by intralysosomal accumulation of globotriaosylceramide and other GLYCOSPHINGOLIPIDS in blood vessels throughout the body leading to multi-system complications including renal, cardiac, cerebrovascular, and skin disorders.

Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.

Glycosphingolipids which contain as their polar head group a trisaccharide (galactose-galactose-glucose) moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in ceramide trihexosidase, is the cause of angiokeratoma corporis diffusum (FABRY DISEASE).

Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (DISEASE VECTORS) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks.

Analyses for a specific enzyme activity, or of the level of a specific enzyme that is used to assess health and disease risk, for early detection of disease or disease prediction, diagnosis, and change in disease status.

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