A Study of Fabrazyme in Pediatric Patients With Fabry Disease

• Sponsor: Genzyme, a Sanofi Company
• Information provided by: Sanofi

Study Description

Brief Summary:

People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-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 a-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 study explored the safety, efficacy and pharmacokinetics of Fabrazyme in pediatric patients aged between 7 and 15 years.

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: Fabrazyme (agalsidase beta)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Phase 2, Open-Label Study of Fabrazyme (Recombinant Human a-Galactosidase A) Replacement Therapy in Pediatric Patients With Fabry Disease
• Study Start Date: October 2002
• Actual Primary Completion Date: May 2005
• Actual Study Completion Date: July 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fabrazyme; 1.0 mg/kg of Fabrazyme given to the patients every 2 weeks	Biological: Fabrazyme (agalsidase beta); 1 mg/kg every 2 weeks; Other Name: r-hαGAL

Outcome Measures

Primary Outcome Measures :

1. Globotriaosylceramide (GL-3) Clearance in Capillary Endothelium in the Skin [ Time Frame: Baseline, Week 24 and Week 48 ]
   Skin biopsies were taken at Baseline, Week 24 and Week 48 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).

Secondary Outcome Measures :

1. Plasma GL-3 [ Time Frame: Baseline, Week 24 and Week 48 ]
   Plasma GL-3 values at Baseline, Week 24, and Week 48. Normal plasma GL-3 level is ≤ 7.03 µg/mL.

Eligibility Criteria

• Ages Eligible for Study: 7 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• Patient or legal guardian must provide written informed consent
• Patients must have a clinical diagnosis of Fabry disease and active Fabry disease (clinical signs and symptoms)
• Patients must be at least 7 years of age but no older than 15 years of age at time of enrollment
• Patients must be Tanner Stage ≤ III
• Female patients must have a negative pregnancy test prior to each infusion and use a medically accepted form of contraception throughout the study

Exclusion Criteria:

• Patient has a clinically significant organic disease (with the exception of symptoms relating to Fabry disease) that in the opinion of the investigator would preclude participation in the trial
• Patient has participated in a study employing investigational drug within 30 days of the start of this study
• Patient has received prior treatment with enzyme replacement therapy
• Patient is unable to comply with the clinical protocol

Contacts and Locations

Locations

United States, Arizona

University of Arizona

Tucson, Arizona, United States, 85724

France

Hopital Edouard Herriot

Lyon, France, Cedex 03

Hopital de la Timone Enfants

Marseille, France, Cedex 05

Hopital Europeen Georges Pompidou

Paris, France, Cedex 15

Poland

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, Poland, 04-730

United Kingdom

Royal Manchester Children's Hospital

Pendlebury, Manchester, United Kingdom, M27 4HA

Great Ormond Street Hospital for Sick Children

London, United Kingdom, WC1N 3JH

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor; Genzyme, a Sanofi Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wraith JE, Tylki-Szymanska A, Guffon N, Lien YH, Tsimaratos M, Vellodi A, Germain DP. Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr. 2008 Apr;152(4):563-70, 570.e1. doi: 10.1016/j.jpeds.2007.09.007. Epub 2007 Dec 3.

• Responsible Party: Medical Monitor, Genzyme Corporation
• ClinicalTrials.gov Identifier: NCT00074958 History of Changes
• Other Study ID Numbers: AGAL-016-01
• First Posted: December 25, 2003
• Results First Posted: June 16, 2009
• Last Update Posted: April 2, 2015
• Last Verified: March 2015

Keywords provided by Sanofi:

a-Galactosidase A; aGal; r-haGAL; Fabry; GL-3; Fabrazyme

Additional relevant MeSH terms:

Fabry Disease; 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; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders