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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Praha 2, Czech Republic, 128 02
    • II. interní klinika 1. LF UK
• Estonia
  • Tartu, Estonia, 51014
    • Tartu University Clinics, Department of Internal Medicine
• Poland
  • Warsaw, Poland, 04-736
    • Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
• Slovakia
  • Bratislava 37, Slovakia, 833 40
    • Detská fakultná nemocnica Kramáre I. Interná klinika

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: r-hαGAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium	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).	Throughout study; 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium	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).	Throughout study ; 96 weeks
Estimated Glomerular Filtration Rate (eGFR)	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	Throughout study; 96 weeks
Plasma Globotriaosylceramide (GL-3)	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.	Throughout study; 96 weeks
Urine Globotriaosylceramide (GL-3)	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.	Throughout study, 96 weeks

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): April 1, 2006
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: aGAL; Fabry; Fabrazyme; alpha Galactosidase A; rh aGAL; GL3
• 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: AGAL-017-01