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

April 8, 2021 updated by: CENTOGENE GmbH Rostock

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®.

Study Overview

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.

Study Type

Observational

Enrollment (Actual)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Observation
Hemizygous male or heterozygous female patients of any age with genetically confirmed diagnosis of Anderson-Fabry disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy and Safety of Switch Between Agalsidase Beta to Agalsidase Alfa for Enzyme Replacement in Patients With Anderson-Fabry Disease
Time Frame: 24 month
24 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Arndt Rolfs, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2010

Primary Completion (ACTUAL)

April 1, 2016

Study Completion (ACTUAL)

April 1, 2016

Study Registration Dates

First Submitted

December 28, 2010

First Submitted That Met QC Criteria

December 28, 2010

First Posted (ESTIMATE)

December 29, 2010

Study Record Updates

Last Update Posted (ACTUAL)

April 9, 2021

Last Update Submitted That Met QC Criteria

April 8, 2021

Last Verified

April 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Fabry Disease

3
Subscribe