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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 (SWITCH)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01268241
First received: December 28, 2010
Last updated: April 12, 2016
Last verified: April 2016
  Purpose
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®.

Condition
Fabry Disease
Fabry´s Disease
Anderson-Fabry Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Rostock:

Primary Outcome Measures:
  • Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Patients With Anderson-Fabry Disease [ Time Frame: 24 month ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
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)

Enrollment: 200
Study Start Date: December 2010
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Observation
Hemizygous male or heterozygous female patients of any age with genetically confirmed diagnosis of Anderson-Fabry disease.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Hemizygous male or heterozygous female patients at 18 years with genetically confirmed diagnosis of Anderson-Fabry disease
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268241

Locations
Argentina
Juan Fernandez Hospital, Department of Neurology
Buenos Aires, Argentina, Cerviño 3356
Unidad Renal Corrientes SRL, Medicina Interna Nefrólogo
Corrientes, Argentina, CP N°3400
Belgium
UZA - University Ziekenhuis Antwerpen)
Edegem, Belgium, 2650
Croatia
University Hospital "Sestre Milosrdnice" Department of neuroimmunology and neurogenetic
Zagreb, Croatia, 10000
Czech Republic
Miroslava Hajkova, 2nd Dept of Cardiology&Angiology, Fakultni poliklinika
Prague 2, Czech Republic, 12800
Denmark
National University Hosoital Rigshospitalet, Endokrinologisk ward
Copenhagen, Denmark, 2100
France
Université de Versailles - Saint Quentin en YvelinesService de Génétique Médicale
Paris - Garches, France, 92380
Germany
Kinderklinik München-Schwabing Städt. Klinikum GmbH
Munich, Germany, 80804
United Kingdom
Royal Free Hospital, Dep. of Academic Haematology, Lysosomal Storage Disorders Unit
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
University of Rostock
Investigators
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Publications:

Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier: NCT01268241     History of Changes
Other Study ID Numbers: SW02/2010 
Study First Received: December 28, 2010
Last Updated: April 12, 2016
Health Authority: Germany: Ethics Commission
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Rostock:
Fabry Disease
Fabry´s Disease
Anderson-Fabry Disease

Additional relevant MeSH terms:
Fabry Disease
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
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Sphingolipidoses
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on September 23, 2016