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

Phase 2

Completed

Conditions: Fabry Disease

Interventions: Biological: Fabrazyme (agalsidase beta)

Registration Number: NCT00196716

Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 21

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fabrazyme	Fabrazyme (agalsidase beta)	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.

Primary Outcome Measures

Name	Time	Method
Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium	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 Outcome Measures

Name	Time	Method
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium	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).
Estimated Glomerular Filtration Rate (eGFR)	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
Plasma Globotriaosylceramide (GL-3)	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.
Urine Globotriaosylceramide (GL-3)	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.

Trial Locations

Locations (4): II. interní klinika 1. LF UK
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Praha 2, Czech Republic
Tartu University Clinics, Department of Internal Medicine
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Tartu, Estonia
Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
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Warsaw, Poland
Detská fakultná nemocnica Kramáre I. Interná klinika
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Bratislava 37, Slovakia