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NCT Number: NCT00196716

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

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.

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Key information

Conditions

Fabry Disease Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Cardiovascular Diseases Central Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities 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 Nutritional and Metabolic Diseases Sphingolipidoses Vascular Diseases

Age range

16 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

II. interní klinika 1. LF UK, Prague, Czechia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fabrazyme (agalsidase beta)

Biological

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 names: r-hαGAL

Primary outcomes

  1. Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium

    Time frame: Throughout study; 96 weeks

    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 outcomes

  1. Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium

    Time frame: Throughout study ; 96 weeks

    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).

  2. Estimated Glomerular Filtration Rate (eGFR)

    Time frame: Throughout study; 96 weeks

    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

  3. Plasma Globotriaosylceramide (GL-3)

    Time frame: Throughout study; 96 weeks

    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.

  4. Urine Globotriaosylceramide (GL-3)

    Time frame: Throughout study, 96 weeks

    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.

Sponsors and collaborators

Lead sponsor

Genzyme, a Sanofi Company

Industry

Registry information

Official study 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

Important dates

Study start
2003
Primary completion
2006
Study completion
2007
First posted
Sep 20, 2005
Registry last updated
Apr 3, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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