A Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) 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 (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 IV

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:

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

U.S. FDA Resources

Further study details as provided by Genzyme:

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

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

Show 26 Study Locations

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme Coorporation

More Information

Additional Information:

Link to Result synopsis for AGAL00800 This link exits the ClinicalTrials.gov site

No publications provided by Genzyme

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:	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:	November 18, 2010
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 Genzyme:

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

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 February 12, 2012