A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease - Full Text View

Sponsored by:	Genzyme
Information provided by:	Genzyme
ClinicalTrials.gov Identifier:	NCT00196716

Purpose

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.

Condition	Intervention	Phase
Fabry Disease	Biological: Fabrazyme (agalsidase beta)	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Fabry disease Farber lipogranulomatosis L1 syndrome primary carnitine deficiency succinic semialdehyde dehydrogenase deficiency

Drug Information available for: alpha-Galactosidase

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium [ Time Frame: Throughout study; 96 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium [ Time Frame: Throughout study ; 96 weeks ] [ Designated as safety issue: No ]
Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Throughout study; 96 weeks ] [ Designated as safety issue: No ]
Plasma Globotriaosylceramide (GL-3) [ Time Frame: Throughout study; 96 weeks ] [ Designated as safety issue: No ]
Urine Globotriaosylceramide (GL-3) [ Time Frame: Throughout study, 96 weeks ] [ Designated as safety issue: No ]

Enrollment:	21
Study Start Date:	June 2003
Study Completion Date:	March 2007
Primary Completion Date:	April 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Fabrazyme: Experimental Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.	Biological: Fabrazyme (agalsidase beta) 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00196716

Locations

Czech Republic
II. interní klinika 1. LF UK
Praha 2, Czech Republic, 128 02
Estonia
Tartu University Clinics, Department of Internal Medicine
Tartu, Estonia, 51014
Poland
Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
Warsaw, Poland, 04-736
Slovakia
Detská fakultná nemocnica Kramáre I. Interná klinika
Bratislava 37, Slovakia, 833 40

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided

Responsible Party:	Genzyme Corporation ( Medical Monitor )
Study ID Numbers:	AGAL-017-01
Study First Received:	September 12, 2005
Results First Received:	December 5, 2008
Last Updated:	August 11, 2009
ClinicalTrials.gov Identifier:	NCT00196716 History of Changes
Health Authority:	Estonia: The State Agency of Medicine; Czech Republic: State Institute for Drug Control; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Slovakia: State Institute for Drug Control

Keywords provided by Genzyme:

alpha Galactosidase A
aGAL
rh aGAL

Fabry
GL3
Fabrazyme

Study placed in the following topic categories:

Lipid Metabolism, Inborn Errors
Sphingolipidoses
Metabolic Diseases
Lysosomal Storage Diseases
Sphingolipidosis
Central Nervous System Diseases
Brain Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn

Fabry Disease
Genetic Diseases, X-Linked
Ceramide Trihexosidosis
Brain Diseases, Metabolic, Inborn
Lipidoses
Metabolic Disorder
Lipid Metabolism Disorders
Brain Diseases, Metabolic

Additional relevant MeSH terms:

Lipid Metabolism, Inborn Errors
Sphingolipidoses
Metabolic Diseases
Lysosomal Storage Diseases, Nervous System
Lysosomal Storage Diseases
Nervous System Diseases
Central Nervous System Diseases
Brain Diseases

Metabolism, Inborn Errors
Genetic Diseases, Inborn
Fabry Disease
Genetic Diseases, X-Linked
Brain Diseases, Metabolic, Inborn
Lipidoses
Lipid Metabolism Disorders
Brain Diseases, Metabolic

ClinicalTrials.gov processed this record on September 03, 2009