Clinical trial NCT00196716: A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fabry Disease
Keywords: alpha Galactosidase A
aGAL
rh aGAL
Fabry
GL3
Fabrazyme
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 21
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
timeFrame: Throughout study; 96 weeks
Secondary outcomes:
measure: Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
timeFrame: Throughout study ; 96 weeks
measure: Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Throughout study; 96 weeks
measure: Plasma Globotriaosylceramide (GL-3)
timeFrame: Throughout study; 96 weeks
measure: Urine Globotriaosylceramide (GL-3)
timeFrame: Throughout study, 96 weeks
Other outcomes:
Locations:
city: Praha 2
country: Czech Republic
facility: II. interní klinika 1. LF UK
city: Tartu
country: Estonia
facility: Tartu University Clinics, Department of Internal Medicine
city: Warsaw
country: Poland
facility: Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
city: Bratislava 37
country: Slovakia
facility: Detská fakultná nemocnica Kramáre I. Interná klinika
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: