The Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Patients With Anderson-Fabry Disease (SWITCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Rostock
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01268241
First received: December 28, 2010
Last updated: June 3, 2014
Last verified: June 2014

December 28, 2010
June 3, 2014
November 2010
June 2014   (final data collection date for primary outcome measure)
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Not Provided
Complete list of historical versions of study NCT01268241 on ClinicalTrials.gov Archive Site
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The Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Patients With Anderson-Fabry Disease
International Observational Retrospective Case Review of Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Males and Females With Anderson-Fabry Disease

The current approved treatment for Fabry disease is enzyme replacement therapy (ERT). There are actually 2 products in this therapeutic class available: Replagal® (agalsidase alfa) and Fabrazyme® (agalsidase beta). Both are indicated for long-term treatment in patients with a confirmed diagnosis of Fabry disease (alfa-galactosidase A deficiency). Both have been commercially available in Europe for almost 10 years, yet little information is available about the clinical and safety profile of patients who switch from one therapy to the other. An extended shortage of Fabrazyme® that began in June 2009 has necessitated that a large number of patients switch from Fabrazyme® to Replagal®. This offers the possibility to study the clinical status and adverse events in patients who switch from Fabrazyme® to Replagal® on a large-scale basis. In addition, as a result of the increasing Fabrazyme® shortage, many of these patients received a reduced dosage of Fabrazyme® for an extended period before transitioning to treatment with Replagal®.

Aim:

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of the hydrolytic enzyme alfa galactosidase A. Trials of specific therapy by replacement of alfa galactosidase A were commenced in 1999 and subsequently two preparations of alfa galactosidase A received marketing approval by the EMEA in 2001. Clinical trials, observational studies and registry data have provided evidence for efficacy of enzyme replacement therapy (ERT) with alfa galactosidase A in improving symptoms of pain, gastrointestinal disturbance, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life in men. There is currently no long-term data showing the impact of enzyme replacement therapy on overall survival. It has been suggested that earlier therapy, before the onset of end organ manifestations, would be more likely to prevent further damage and therefore have the biggest effect on overall survival. There is as yet little evidence to substantiate this hypothesis however clinical trials have recently demonstrated safety and therapeutic effects of enzyme replacement in children.

So far, there are only limited data available on the clinical course of the disease and adverse events in patients, switching from one therapeutic alternative to the other. West and Lemoine (16) report clinical effects of a switch from Agalsidase beta to agalsidase alfa in 5 patients with Fabry disease due to shortage of agalsidase beta. The patients were treated with Replagal® for 44 weeks at an average.

Observational
Observational Model: Cohort
Not Provided
Retention:   Samples With DNA
Description:

Plasma and urine GB3 and lyso-GB3 and agalsidase antibodies will be analyzed in central laboratories, there is consent for extra blood samples to be taken (at the time of the switch and after 6, 12 and 24 months)

Probability Sample

Hemizygous male or heterozygous female patients at 18 years with genetically confirmed diagnosis of Anderson-Fabry disease

  • Fabry Disease
  • Fabry´s Disease
  • Anderson-Fabry Disease
Not Provided
Observation
Hemizygous male or heterozygous female patients of any age with genetically confirmed diagnosis of Anderson-Fabry disease.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
June 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Hemizygous male or heterozygous female patients at 18 years with genetically confirmed diagnosis of Anderson-Fabry disease.
  • Written informed consent
  • Patient had received Fabrazyme® for at least 12 months prior to starting treatment with Replagal® in full dose (i.e. 1.0 mg/kg eow) or any reduced dose prescribed by the treating physician due to the shortage of the medication
  • Patient has received or is receiving treatment commercially available Replagal® (0.2 mg/kg eow) for intravenous (IV) infusion prescribed by their treatment physician and administered in accordance with the Replagal® prescribing information.
  • The switch of the medication from Fabrazyme® to Replagal® had to be taken place from September 2009 onwards at the earliest
  • Patient data includes disease history, measures of Fabry related disease and safety measures

Exclusion Criteria:

  • Concomitant use of Fabrazyme®
  • Any switch of medication from Fabrazyme® to Replagal® before September 2009
  • Any switch from Fabrazyme® to Replagal® for other reasons than Fabrazyme® shortage
  • Patient has received treatment with any investigational drug or device within the 30 days prior to study entry
  • No written informed consent
Both
18 Years and older
No
Contact: Arndt Rolfs, MD 49-381-494 ext 9540 arndt.rolfs@med.uni-rostock.de
Contact: Kristin Bruederlein 49-381-494 ext 4737 kristin.bruederlein@med.uni-rostock.de
Argentina,   Belgium,   Croatia,   Czech Republic,   Denmark,   France,   Germany,   United Kingdom
 
NCT01268241
SW02/2010
Yes
Prof. Dr. Arndt Rolfs, University of Rostock
University of Rostock
Not Provided
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
University of Rostock
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP