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

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00196716
First received: September 12, 2005
Last updated: March 17, 2015
Last verified: March 2015
  Purpose

People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. This enzyme helps to break down and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In people with Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because alpha-galactosidase A is not present, or is present in small quantities. The build up of glycolipid levels (also referred to as "globotriaosylceramide" or "GL-3") in these tissues is thought to cause the clinical symptoms that are common to Fabry disease. Symptoms commonly appear during childhood with pain in the hands and feet. This trial is designed to evaluate the efficacy of a lower dose of Fabrazyme in patients who initially received 1.0 mg/kg every 2 weeks of Fabrazyme by investigating if the achieved clearance of glycosphingolipid deposits in the vascular endothelium of the kidney can be maintained at a lower dose.


Condition Intervention Phase
Fabry Disease
Biological: Fabrazyme (agalsidase beta)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label Study of Low Dose Maintenance Treatment of Fabrazyme (Recombinant Human Alpha-Galactosidase A (R-h Alpha-GAL)) Replacement Therapy in Patients With Fabry Disease

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium [ Time Frame: Throughout study; 96 weeks ] [ Designated as safety issue: No ]
    Kidney biopsies were taken at Baseline, Week 24, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).


Secondary Outcome Measures:
  • Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium [ Time Frame: Throughout study ; 96 weeks ] [ Designated as safety issue: No ]
    Skin biopsies were taken at Baseline, Week 24, Week 48, Week 72, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).

  • Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Throughout study; 96 weeks ] [ Designated as safety issue: No ]
    Evaluated at Baseline, Week 24 and Week 96. eGFR is an estimation of the glomerular filtration rate of the kidneys (how much blood the kidneys are filtering). For this study, normal eGFR was defined as greater than 90 mL/min/1.73 m2

  • Plasma Globotriaosylceramide (GL-3) [ Time Frame: Throughout study; 96 weeks ] [ Designated as safety issue: No ]
    Evaluated at Baseline, Week 24, Week 48, Week 72 and Week 96. Plasma GL-3 is often elevated in the plasma of patients diagnosed with Fabry disease. This outcome measure evaluated the mean plasma GL-3 values for all patients to see if it decreased while on Fabrazyme. Normal plasma GL-3 level was <= 7.03 µg/mL.

  • Urine Globotriaosylceramide (GL-3) [ Time Frame: Throughout study, 96 weeks ] [ Designated as safety issue: No ]
    Evaluated at Baseline, Week 24 and Week 96. Urine GL-3 is often elevated in the urine of patients diagnosed with Fabry disease. This outcome measure evaluated the mean urine GL-3 in first morning void urine for all patients to see if it decreased while on Fabrazyme. Normal Urine GL-3 threshold was < 8.8 μg/mg.


Enrollment: 21
Study Start Date: June 2003
Study Completion Date: March 2007
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fabrazyme
Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Biological: Fabrazyme (agalsidase beta)
1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months
Other Name: r-hαGAL

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have clinical manifestations of Fabry disease
  • All patients have to have a plasma αGAL activity of < 1.5 nmol/hr/mL or a documented leukocyte αGAL activity of < 4 nmol/hr/mg
  • Patient or patient's parent/guardian had to provide written informed consent prior to any study-related procedures being performed
  • Patients had to be male and ≥ 16 years of age

Exclusion Criteria:

  • There is evidence of renal insufficiency, as defined by serum creatinine greater than or equal to 2.2 mg/dL (194.7 μmol/L) AND/OR has an estimated glomerular filtration rate (GFR) of <80 mL/min (using the equation derived from the Modification of Diet in Renal Disease Study (MDRD))
  • Has undergone kidney transplantation or is currently on dialysis
  • Has a clinically significant organic disease or an unstable condition (with the exception of symptoms relating to Fabry disease) that in the opinion of the Investigator would preclude participation in the trial
  • Has participated in a study employing an investigational drug within 30 days of the start of this trial
  • Patients who received prior treatment with enzyme replacement therapy for Fabry disease
  • Patient was unable to comply with the requirements of the protocol
  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: NCT00196716

Locations
Czech Republic
II. interní klinika 1. LF UK
Praha 2, Czech Republic, 128 02
Estonia
Tartu University Clinics, Department of Internal Medicine
Tartu, Estonia, 51014
Poland
Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
Warsaw, Poland, 04-736
Slovakia
Detská fakultná nemocnica Kramáre I. Interná klinika
Bratislava 37, Slovakia, 833 40
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00196716     History of Changes
Other Study ID Numbers: AGAL-017-01
Study First Received: September 12, 2005
Results First Received: December 5, 2008
Last Updated: March 17, 2015
Health Authority: Estonia: The State Agency of Medicine
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control

Keywords provided by Sanofi:
alpha Galactosidase A
aGAL
rh aGAL
Fabry
GL3
Fabrazyme

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

ClinicalTrials.gov processed this record on May 28, 2015