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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00074984
First received: December 24, 2003
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Fabry Disease
Biological: Fabrazyme (agalsidase beta)
Biological: Placebo
Phase 4

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


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
    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:
  • Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
    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.

  • Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients [ Time Frame: up to 35 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: at 24 months ] [ Designated as safety issue: No ]
    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)


Enrollment: 82
Study Start Date: February 2001
Study Completion Date: January 2004
Primary Completion Date: January 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Patients randomized to placebo
Biological: Placebo
1 mg/kg placebo intravenously every 2 weeks
Active Comparator: Fabrazyme (agalsidase beta)
Patients randomized to Fabrazyme (agalsidase beta).
Biological: Fabrazyme (agalsidase beta)
1mg/kg Fabrazyme (agalsidase beta) every 2 weeks
Other Name: Fabrazyme

  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 26 Study Locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme Coorporation
  More Information

Additional Information:
No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medical Monitor, Genzyme Coporation
ClinicalTrials.gov Identifier: NCT00074984     History of Changes
Other Study ID Numbers: AGAL-008-00
Study First Received: December 24, 2003
Results First Received: July 21, 2010
Last Updated: December 2, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Hungary: National Institute of Pharmacy
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sanofi:
a-Galactosidase A
aGAL
r-haGAL
Fabry
GL-3
Fabrazyme

Additional relevant MeSH terms:
Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on July 31, 2014