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

Fabry Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00074984
• Other study ID #: AGAL-008-00
• Status: Completed
• Phase: Phase 4
• First received: December 24, 2003
• Last updated: December 2, 2013
• Start date: February 2001
• Est. completion date: January 2004

Study information

• Verified date: December 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaHungary: National Institute of PharmacyCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: January 2004
• Est. primary completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• Fabrazyme (agalsidase beta)
1mg/kg Fabrazyme (agalsidase beta) every 2 weeks
• Placebo
1 mg/kg placebo intravenously every 2 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada,  Czech Republic,  Hungary,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	up to 35 months	No
Secondary	Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients	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.	up to 35 months	No
Secondary	Slope of Estimated Glomerular Filtration Rate (eGFR) Comparing Placebo vs Fabrazyme (Agalsidase Beta) Patients	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.	up to 35 months	No
Secondary	Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients	Summary of slopes of inverse serum creatinine by baseline serum creatinine subgroups (> or <= 1.5 mg/dL) comparing Placebo vs Fabrazyme (agalsidase beta) patients.	up to 35 months	No
Secondary	Neuropathic Pain as Assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (Pain at Its Worst)	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)	at 24 months	No