A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease

Multi-Center, Open-Label Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease That Previously Participated in the AGAL-008-00 Study

People with Fabry Disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to break down and removes 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 (globatriaosylceramide or GL-3) levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study analyzed the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease that previously participated in the AGAL-008-00 (NCT0074984) study.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: agalsidase beta

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Queen Elizabeth II Health Center
  • Ontario
    • Toronto, Ontario, Canada, M2K 1E1
      • North York General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal
• Czech Republic
  • Prague, Czech Republic
    • University Hospital
• Hungary
  • Sopron, Hungary, 9400
    • Sopron Megyei Jogu Varos Erzsebet Korhaz
• Poland
  • Warsaw, Poland, 04-730
    • Klinika Chorob Metabolicznych Instytut
• United Kingdom
  • Manchester, United Kingdom, M6 8HD
    • Hope Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • San Francisco, California, United States, 94143
      • University of San Francisco
  • Connecticut
    • West Hartford, Connecticut, United States, 06119
      • University of Connecticut Health Partners
  • Florida
    • Coral Springs, Florida, United States, 33065
      • Oncology Hematology Association
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School Of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160-7233
      • University Of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Gene Therapy Center - Department of Pediatrics and Institute of Human Genetics
  • New York
    • Buffalo, New York, United States, 14209
      • Children's Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have successfully completed the previous double-blind study AGAL-008-00 (NCT00074984)
• Patients must provide written informed consent prior to study participation
• 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 throughout the study

Exclusion Criteria:

• The patient was unable to complete AGAL-008-00 (NCT00074984)
• The patient has undergone kidney transplantation or is currently on dialysis
• The patient has diabetes mellitus or presence of confounding renal disease
• The patient has a clinically significant organic disease or an unstable condition that precludes participation
• The patient is unwilling to comply with the protocol requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fabrazyme 1.0 mg/kg every 2 weeks; This is an open-label extension study to AGAL-008-00 (NCT00074984) and all patients received Fabrazyme treatment.	Biological: agalsidase beta; 1.0 mg/kg every 2 weeks; Other Names: Fabrazyme; r-hαGAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Inverse Serum Creatinine Within Patients' Slopes Between the Placebo AGAL-008-00 (NCT00074984) and Fabrazyme AGAL02503 (NCT00081497) Periods	The primary efficacy analysis was the summary of change in slope of inverse serum creatinine for Placebo/Fabrazyme patients in the Intent to Treat (ITT) Population. It compared the placebo period slope with the Fabrazyme period slope.	Placebo period AGAL-008-00 (up to 35 months) through Fabrazyme period AGAL02503 (18 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Creatinine at Pre-Fabrazyme and 6, 12, and 18 Months	Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).	Pre-Fabrazyme, 6, 12, and 18 months
Estimated Glomerular Filtration Rate (eGFR) at Pre-Fabrazyme and 6, 12, and 18 Months	Pre-Fabrazyme=baseline visit of AGAL-00-800 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).	Pre-Fabrazyme, 6, 12, and 18 months
Plasma Globotriaosylceramide (GL-3) (Normal Plasma GL-3 Level is ≤ 7.03 µg/mL) at Pre-Fabrazyme and 6, 12, and 18 Months	Pre-Fabrazyme=baseline visit of AGAL00800 for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL00800; assessment prior to first Fabrazyme infusion in AGAL02503 for placebo patients who did not transition to Fabrazyme in AGAL00800.	Pre-Fabrazyme and 6, 12, and 18 months
Proteinuria at Pre-Fabrazyme and 6, 12, and 18 Months	Pre-Fabrazyme=baseline visit of AGAL-008-00 (NCT00074984) for Fabrazyme patients; assessment prior to open-label for placebo patients who transitioned to Fabrazyme in AGAL-008-00 (NCT00074984); assessment prior to first Fabrazyme infusion in AGAL02503 (NCT00081497) for placebo patients who did not transition to Fabrazyme in AGAL-008-00 (NCT00074984).	Pre-Fabrazyme and 6, 12, and 18 months

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): September 1, 2005
• Study Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: April 14, 2004
• First Submitted That Met QC Criteria: April 15, 2004
• First Posted (Estimate): April 16, 2004

Study Record Updates

• Last Update Posted (Estimate): April 2, 2015
• Last Update Submitted That Met QC Criteria: March 13, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: r-haGAL; Fabry; GL-3; Fabrazyme; alpha-galactosidase A; a-GAL
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: AGAL02503