Clinical trial NCT00074984: A Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) as Compared to Placebo in Patients With Advanced Fabry Disease
Official title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Fabrazyme on Progression of Renal Disease and Significant Clinical Events in Patients With Fabry Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fabry Disease
Keywords: a-Galactosidase A
aGAL
r-haGAL
Fabry
GL-3
Fabrazyme
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2003-12-25
Enrollment: 82
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to breakdown and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid ("globotriaosylceramide" or "GL-3") levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study will test the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease.


Eligibility criteria: Inclusion Criteria:

* Patients must provide written informed consent
* Patients must be at least 16 years old
* Patients must have a current diagnosis of Fabry disease and have a clinical presentation consistent of Fabry disease (decreased sweating, Fabry pain, angiokeratoma, etc.)
* Patients may not have received enzyme replacement therapy as a treatment for Fabry disease
* Patients must have a documented plasma a-galactosidase A (aGAL) activity of \< 1.5 nmol/hr/mL or a documented leukocyte aGAL activity of \< 4 nmol/hr/mg
* Patients must have one or more of the following: a serum creatinine measurement of 1.2 to 3 mg/dL (106.1 to 265 umol/L) OR estimated creatinine clearance \< 80 mL/min only if the patient's serum creatinine measurement is \< 1.2 mg/dL
* Female patients of childbearing potential must have a negative pregnancy test prior to each dosing and all female patients must use a medically accepted form of contraception

Exclusion Criteria:

* Patient has undergone or is currently scheduled for kidney transplantation or is currently on dialysis
* Patient has acute renal failure
* Patient has participated in a study employing an investigational drug within 30 days of study entry
* Patient has diabetes mellitus or presence of confounding renal disease
* Patient has a history of transient ischemic attack (TIA) or ischemic stroke within 3 months of study entry documented by mild-to-moderate neurological deficit
* Patient has critical coronary disease
* Patient has congestive heart failure
* Patient has severe residual neurological deficit that will confound the detection of new events as determined by an attending neurologist and/or Principal Investigator
* Patient is unwilling to comply with the requirements of the protocol or the patient has a medical condition, serious intercurrent illness, or extenuating circumstances that would significantly decrease study compliance, including prescribed follow-up

Primary outcomes:
measure: Number of Participants Experiencing a Clinically Significant Renal, Cardiac or Cerebrovascular Event and/or Death in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients
timeFrame: up to 35 months
Secondary outcomes:
measure: Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients
timeFrame: up to 35 months
measure: Slope of Estimated Glomerular Filtration Rate (eGFR) Comparing Placebo vs Fabrazyme (Agalsidase Beta) Patients
timeFrame: up to 35 months
measure: Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients
timeFrame: up to 35 months
measure: Neuropathic Pain as Assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (Pain at Its Worst)
timeFrame: at 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of San Francisco
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Partners
state: Connecticut
city: Coral Springs
country: United States
facility: Oncology Hematology Association
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Gene Therapy Center - Dept. of Pediatrics and Institute of Human Genetics
state: Minnesota
city: Buffalo
country: United States
facility: Children's Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester School of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Center
state: Nova Scotia
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Prague
country: Czech Republic
facility: University Hospital
city: Sopron
country: Hungary
facility: Sopron Megyei Jogu Varos Erzsebet Korhaz
city: Warsaw
country: Poland
facility: Klinika Chorob Metabolicznych Instytut
city: Manchester
country: United Kingdom
facility: Hope Hospital
Study officials:
affiliation: Genzyme Coorporation
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ; Fabry Disease Clinical Trial Study Group. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007 Jan 16;146(2):77-86. doi: 10.7326/0003-4819-146-2-200701160-00148. Epub 2006 Dec 18.