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

NCT00074984 | Completed Phase 4 Results DMC

• 1 other identifier: AGAL-008-00
• Study Type: interventional
• Target: 82
• Locations: 6 countries
• Sites: 26

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.

Conditions

Fabry Disease

Keywords

a-Galactosidase A; aGAL; r-haGAL; Fabry; GL-3; Fabrazyme

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients

  up to 35 months

• Slope of Estimated Glomerular Filtration Rate (eGFR) Comparing Placebo vs Fabrazyme (Agalsidase Beta) Patients

  up to 35 months

• Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients

  up to 35 months

• Neuropathic Pain as Assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (Pain at Its Worst)

  at 24 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients randomized to placebo

Biological: Placebo

Fabrazyme (agalsidase beta)

ACTIVE COMPARATOR

Patients randomized to Fabrazyme (agalsidase beta).

Biological: Fabrazyme (agalsidase beta)

Interventions

Fabrazyme (agalsidase beta) BIOLOGICAL

1mg/kg Fabrazyme (agalsidase beta) every 2 weeks

Also known as: Fabrazyme

Fabrazyme (agalsidase beta)

Placebo BIOLOGICAL

1 mg/kg placebo intravenously every 2 weeks

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (26)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of San Francisco

San Francisco, California, 94143, United States

Location

University of Connecticut Health Partners

Farmington, Connecticut, 06119, United States

Location

Oncology Hematology Association

Coral Springs, Florida, 33065, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Gene Therapy Center - Dept. of Pediatrics and Institute of Human Genetics

Minneapolis, Minnesota, 55455, United States

Location

Children's Hospital

Buffalo, New York, 14209, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Rochester School of Medicine

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98195, United States

Location

Queen Elizabeth II Health Center

Halifax, Nova Scotia, B3H 1V8, Canada

Location

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

Location

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

University Hospital

Prague, 128 08, Czechia

Location

Sopron Megyei Jogu Varos Erzsebet Korhaz

Sopron, 9400, Hungary

Location

Klinika Chorob Metabolicznych Instytut

Warsaw, 04-730, Poland

Location

Hope Hospital

Manchester, M6 8HD, United Kingdom

Location

Related Publications (1)

• 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. doi: 10.7326/0003-4819-146-2-200701160-00148. Epub 2006 Dec 18.

  PMID: 17179052 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

agalsidase beta

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

800-745-4447

Study Officials

• Medical Monitor

  Genzyme Coorporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 24, 2003
• First Posted: December 25, 2003
• Study Start: February 1, 2001
• Primary Completion: January 1, 2004
• Study Completion: January 1, 2004
• Last Updated: December 27, 2013
• Results First Posted: December 15, 2010

Record last verified: 2013-12

Locations

GB (1); CA (3); CZ (1); US (19); HU (1); PL (1)