A Study of the Safety and Efficacy of Fabrazyme as Compared to Placebo in Patients With Advanced Fabry Disease - Full Text View

Sponsor:	Genzyme
Information provided by:	Genzyme
ClinicalTrials.gov Identifier:	NCT00074984

Purpose

People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. Fabrazyme is a drug that helps to breakdown and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid ("globatriaosylceramide" or "GL-3") levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study will test the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease.

Condition	Intervention	Phase
Fabry Disease	Drug: Fabrazyme (agalsidase beta) Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Fabrazyme on Progression of Renal Disease and Significant Clinical Events 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

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Time to the first occurrence of a clinically significant renal, cardiac or cerebrovascular event and/or death in Fabrazyme patients as compared to placebo patients [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

time to first renal event [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
slope of estimated glomerular filtration rate (GFR) [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
slope of inverse serum creatinine values [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
neuropathic pain as assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (pain at its worst) [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]

Enrollment:	82
Study Start Date:	February 2001
Study Completion Date:	June 2004
Primary Completion Date:	January 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo: Placebo Comparator Patients randomized to placebo	Drug: Placebo 1 mg/kg placebo intravenously every 2 weeks
Fabrazyme: Active Comparator Patients randomized to Fabrazyme	Drug: Fabrazyme (agalsidase beta) Fabrazyme 1mg/kg every 2 weeks

Eligibility

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

Criteria

Inclusion Criteria:

Patients must provide written informed consent
Patients must be at least 16 years old
Patients must have a current diagnosis of Fabry disease
Patients may not have received enzyme replacement therapy as a treatment for Fabry disease
Patients must have a documented plasma a-galactosidase A (aGAL) activity of < 1.5 nmol/hr/mL or a documented leukocyte aGAL activity of < 4 nmol/hr/mg
Patients must have one or more of the following: a serum creatinine measurement of 1.2 to 3 mg/dL (106.1 to 265 umol/L) OR estimated creatinine clearance < 80 mL/min only if the patient's serum creatinine measurement is < 1.2 mg/dL
Female patients of childbearing potential must have a negative pregnancy test prior to each dosing and all female patients must use a medically accepted form of contraception

Exclusion Criteria:

Patient has undergone or is currently scheduled for kidney transplantation or is currently on dialysis
Patient has acute renal failure
Patient has participated in a study employing an investigational drug within 30 days of study entry
Patient has diabetes mellitus or presence of confounding renal disease
Patient has a history of TIA or ischemic stroke within 3 months of study entry documented by mild-to-moderate neurological deficit
Patient has critical coronary disease
Patient has congestive heart failure
Patient has severe residual neurological deficit that will confound the detection of new events as determined by an attending neurologist and/or Principal Investigator
Patient is unwilling to comply with the requirements of the protocol or the patient has a medical condition, serious intercurrent illness, or extenuating circumstances that would significantly decrease study compliance, including prescribed follow-up

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074984

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Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
University of San Francisco
San Francisco, California, United States, 94143
United States, Connecticut
University of Connecticut Health Partners
West Hartford, Connecticut, United States, 06119
United States, Florida
Oncology Hematology Association
Coral Springs, Florida, United States, 33065
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Minnesota
Gene Therapy Center - Dept. of Pediatrics and Institute of Human Genetics
Minneapolis, Minnesota, United States, 55455
United States, New York
Children's Hospital
Buffalo, New York, United States, 14209
Mount Sinai School of Medicine
New York, New York, United States, 10029
University of Rochester School of Medicine
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
University of Washington School of Medicine
Seattle, Washington, United States, 98195
Canada, Nova Scotia
Queen Elizabeth II Health Center
Halifax, Nova Scotia, Canada, B3H 1V8
Canada, Ontario
North York General Hospital
Toronto, Ontario, Canada, M2K 1E1
Canada, Quebec
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J 1C5
Czech Republic
University Hospital
Prague, Czech Republic, 128 08
Hungary
Sopron Megyei Jogu Varos Erzsebet Korhaz
Sopron, Hungary, 9400
Poland
Klinika Chorob Metabolicznych Instytut
Warsaw, Poland, 04-730
United Kingdom
Hope Hospital
Manchester, United Kingdom, M6 8HD

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme Coorporation

More Information

No publications provided by Genzyme

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ; Fabry Disease Clinical Trial Study Group. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007 Jan 16;146(2):77-86. Epub 2006 Dec 18.

Responsible Party:	Genzyme Coporation ( Medical Monitor )
Study ID Numbers:	AGAL-008-00
Study First Received:	December 24, 2003
Last Updated:	October 9, 2009
ClinicalTrials.gov Identifier:	NCT00074984 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genzyme:

a-Galactosidase A
aGAL
r-haGAL

Fabry
GL-3
Fabrazyme

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 November 27, 2009