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

Fabry Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00196716
• Other study ID #: AGAL-017-01
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: March 17, 2015
• Start date: June 2003
• Est. completion date: March 2007

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Estonia: The State Agency of MedicineCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: March 2007
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Have clinical manifestations of Fabry disease

• All patients have to have a plasma aGAL activity of < 1.5 nmol/hr/mL or a documented leukocyte aGAL 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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fabry Disease

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

Czech Republic,  Estonia,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No