A Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) as Compared to Placebo in Patients With Advanced Fabry Disease

Phase 4

Completed

Conditions: Fabry Disease

Interventions: Biological: Placebo
Biological: Fabrazyme (agalsidase beta)

Registration Number: NCT00074984

Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary: People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. Fabrazyme (agalsidase beta) 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 ("globotriaosylceramide" 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

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 and have a clinical presentation consistent of Fabry disease (decreased sweating, Fabry pain, angiokeratoma, etc.)
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 transient ischemic attack (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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients randomized to placebo
Fabrazyme (agalsidase beta)	Fabrazyme (agalsidase beta)	Patients randomized to Fabrazyme (agalsidase beta).

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing a Clinically Significant Renal, Cardiac or Cerebrovascular Event and/or Death in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients	up to 35 months	The primary efficacy endpoint was the time to the first occurrence of a clinically significant renal (33% increase in serum creatinine, dialysis or transplant), cardiac (myocardial infarction, significant change in cardiac status, i.e., angina, congestive heart failure or symptomatic arrhythmia requiring medication or surgery) or cerebrovascular (stroke or transient ischemic attack) event and/or death (due to any cause) in Fabrazyme (agalsidase beta) patients as compared to placebo patients.

Secondary Outcome Measures

Name	Time	Method
Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients	up to 35 months	Summary of slopes of inverse serum creatinine by baseline serum creatinine subgroups (\> or \<= 1.5 mg/dL) comparing Placebo vs Fabrazyme (agalsidase beta) patients.
Neuropathic Pain as Assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (Pain at Its Worst)	at 24 months	Neuropathic pain was assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire on a scale of 0 (no pain) to 10 (pain as bad as you can imagine)
Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients	up to 35 months	Time to a clinically significant renal event (33% increase in serum creatinine, dialysis or transplant) in Fabrazyme (agalsidase beta) patients as compared to placebo patients.
Slope of Estimated Glomerular Filtration Rate (eGFR) Comparing Placebo vs Fabrazyme (Agalsidase Beta) Patients	up to 35 months	Summary of slopes of eGFR by baseline eGFR subgroups (\>60 and \<=60 mL/min/1.73m\^2/year) comparing Placebo vs Fabrazyme (agalsidase beta) Patients.

Trial Locations

Locations (26): Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
Children's Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Oncology Hematology Association
🇺🇸
Coral Springs, Florida, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Emory University School of Medicine
🇺🇸
Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Hopital du Sacre-Coeur de Montreal
🇨🇦
Montreal, Quebec, Canada
Children's Hospital
🇺🇸
Buffalo, New York, United States
University of Washington School of Medicine
🇺🇸
Seattle, Washington, United States
Queen Elizabeth II Health Center
🇨🇦
Halifax, Nova Scotia, Canada
Klinika Chorob Metabolicznych Instytut
🇵🇱
Warsaw, Poland
Hope Hospital
🇬🇧
Manchester, United Kingdom
North York General Hospital
🇨🇦
Toronto, Ontario, Canada
University of Rochester School of Medicine
🇺🇸
Rochester, New York, United States
Sopron Megyei Jogu Varos Erzsebet Korhaz
🇭🇺
Sopron, Hungary
University Hospital
🇨🇿
Prague, Czech Republic
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
University of San Francisco
🇺🇸
San Francisco, California, United States
University of Connecticut Health Partners
🇺🇸
Farmington, Connecticut, United States
Gene Therapy Center - Dept. of Pediatrics and Institute of Human Genetics
🇺🇸
Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States