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

NCT00196716 | Completed Phase 2 Results

• 1 other identifier: AGAL-017-01
• Study Type: interventional
• Target: 21
• Locations: 4 countries
• Sites: 4

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.

Conditions

Fabry Disease

Keywords

alpha Galactosidase A; aGAL; rh aGAL; Fabry; GL3; Fabrazyme

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium

  Throughout study ; 96 weeks

• Estimated Glomerular Filtration Rate (eGFR)

  Throughout study; 96 weeks

• Plasma Globotriaosylceramide (GL-3)

  Throughout study; 96 weeks

• Urine Globotriaosylceramide (GL-3)

  Throughout study, 96 weeks

Study Arms (1)

Fabrazyme

EXPERIMENTAL

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)

Interventions

Fabrazyme (agalsidase beta) BIOLOGICAL

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

Also known as: r-hαGAL

Fabrazyme

Eligibility Criteria

• Age: 16 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (4)

II. interní klinika 1. LF UK

Prague, 128 02, Czechia

Location

Tartu University Clinics, Department of Internal Medicine

Tartu, 51014, Estonia

Location

Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"

Warsaw, 04-736, Poland

Location

Detská fakultná nemocnica Kramáre I. Interná klinika

Bratislava, 833 40, Slovakia

Location

MeSH Terms

Conditions

Fabry Disease

Interventions

agalsidase beta

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Genzyme MedInfo
• Organization: Genzyme Corporation

medinfo@genzyme.com

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: June 1, 2003
• Primary Completion: April 1, 2006
• Study Completion: March 1, 2007
• Last Updated: April 3, 2015
• Results First Posted: April 2, 2009

Record last verified: 2015-03

Locations

SL (1); CZ (1); ES (1); PL (1)