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

NCT01268241 | Completed DMC

• 1 other identifier: SW02/2010
• Study Type: observational
• Target: 200
• Locations: 8 countries
• Sites: 9

Brief Summary

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®.

Conditions

Fabry Disease; Fabry´s Disease; Anderson-Fabry Disease

Keywords

Fabry Disease; Fabry´s Disease; Anderson-Fabry Disease

Outcome Measures

Primary Outcomes (1)

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

  24 month

Study Arms (1)

Observation

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CENTOGENE GmbH Rostock: lead

Study Sites (9)

Juan Fernandez Hospital, Department of Neurology

Buenos Aires, Cerviño 3356, Argentina

Location

Unidad Renal Corrientes SRL, Medicina Interna Nefrólogo

Corrientes, CP N°3400, Argentina

Location

UZA - University Ziekenhuis Antwerpen)

Edegem, 2650, Belgium

Location

University Hospital "Sestre Milosrdnice" Department of neuroimmunology and neurogenetic

Zagreb, 10000, Croatia

Location

Miroslava Hajkova, 2nd Dept of Cardiology&Angiology, Fakultni poliklinika

Prague, 12800, Czechia

Location

National University Hosoital Rigshospitalet, Endokrinologisk ward

Copenhagen, 2100, Denmark

Location

Université de Versailles - Saint Quentin en YvelinesService de Génétique Médicale

Paris, 92380, France

Location

Kinderklinik München-Schwabing Städt. Klinikum GmbH

Munich, 80804, Germany

Location

Royal Free Hospital, Dep. of Academic Haematology, Lysosomal Storage Disorders Unit

London, NW3 2QG, United Kingdom

Location

Related Publications (17)

• Rolfs A, Bottcher T, Zschiesche M, Morris P, Winchester B, Bauer P, Walter U, Mix E, Lohr M, Harzer K, Strauss U, Pahnke J, Grossmann A, Benecke R. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005 Nov 19;366(9499):1794-6. doi: 10.1016/S0140-6736(05)67635-0.

  PMID: 16298216 BACKGROUND

• Rolfs A, Martus P, Heuschmann PU, Grittner U, Holzhausen M, Tatlisumak T, Bottcher T, Fazekas F, Enzinger C, Ropele S, Schmidt R, Riess O, Norrving B; sifap1 Investigators. Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a prospective multicenter European study of 5,024 young stroke patients aged 18-55 years. Cerebrovasc Dis. 2011;31(3):253-62. doi: 10.1159/000322153. Epub 2010 Dec 21.

  PMID: 21178350 BACKGROUND

• Kint JA. Fabry's disease: alpha-galactosidase deficiency. Science. 1970 Feb 27;167(3922):1268-9. doi: 10.1126/science.167.3922.1268.

  PMID: 5411915 BACKGROUND

• Mehta A, Ricci R, Widmer U, Dehout F, Garcia de Lorenzo A, Kampmann C, Linhart A, Sunder-Plassmann G, Ries M, Beck M. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest. 2004 Mar;34(3):236-42. doi: 10.1111/j.1365-2362.2004.01309.x.

  PMID: 15025684 BACKGROUND

• MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet. 2001 Nov;38(11):750-60. doi: 10.1136/jmg.38.11.750.

  PMID: 11694547 BACKGROUND

• Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, Gass A, Winston J, Dikman S, Fallon JT, Brodie S, Stacy CB, Mehta D, Parsons R, Norton K, O'Callaghan M, Desnick RJ. A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet. 2001 Mar;68(3):711-22. doi: 10.1086/318809. Epub 2001 Feb 1.

  PMID: 11179018 BACKGROUND

• Schiffmann R, Kopp JB, Austin HA 3rd, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001 Jun 6;285(21):2743-9. doi: 10.1001/jama.285.21.2743.

  PMID: 11386930 BACKGROUND

• Moore DF, Altarescu G, Herscovitch P, Schiffmann R. Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease. BMC Neurol. 2002 Jun 18;2:4. doi: 10.1186/1471-2377-2-4.

  PMID: 12079501 BACKGROUND

• Schiffmann R, Floeter MK, Dambrosia JM, Gupta S, Moore DF, Sharabi Y, Khurana RK, Brady RO. Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve. 2003 Dec;28(6):703-10. doi: 10.1002/mus.10497.

  PMID: 14639584 BACKGROUND

• Hoffmann B, Reinhardt D, Koletzko B. Effect of enzyme-replacement therapy on gastrointestinal symptoms in Fabry disease. Eur J Gastroenterol Hepatol. 2004 Oct;16(10):1067-9. doi: 10.1097/00042737-200410000-00020.

  PMID: 15371935 BACKGROUND

• Hajioff D, Goodwin S, Quiney R, Zuckerman J, MacDermot KD, Mehta A. Hearing improvement in patients with Fabry disease treated with agalsidase alfa. Acta Paediatr Suppl. 2003 Dec;92(443):28-30; discussion 27. doi: 10.1111/j.1651-2227.2003.tb00217.x.

  PMID: 14989462 BACKGROUND

• Hoffmann B, Garcia de Lorenzo A, Mehta A, Beck M, Widmer U, Ricci R; FOS European Investigators. Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey). J Med Genet. 2005 Mar;42(3):247-52. doi: 10.1136/jmg.2004.025791.

  PMID: 15744039 BACKGROUND

• Beck M, Ricci R, Widmer U, Dehout F, de Lorenzo AG, Kampmann C, Linhart A, Sunder-Plassmann G, Houge G, Ramaswami U, Gal A, Mehta A. Fabry disease: overall effects of agalsidase alfa treatment. Eur J Clin Invest. 2004 Dec;34(12):838-44. doi: 10.1111/j.1365-2362.2004.01424.x.

  PMID: 15606727 BACKGROUND

• Banikazemi M, Ullman T, Desnick RJ. Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy. Mol Genet Metab. 2005 Aug;85(4):255-9. doi: 10.1016/j.ymgme.2005.04.009.

  PMID: 15939645 BACKGROUND

• Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ; Fabry Disease Clinical Trial Study Group. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007 Jan 16;146(2):77-86. doi: 10.7326/0003-4819-146-2-200701160-00148. Epub 2006 Dec 18.

  PMID: 17179052 BACKGROUND

• Ramaswami U, Wendt S, Pintos-Morell G, Parini R, Whybra C, Leon Leal JA, Santus F, Beck M. Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr. 2007 Jan;96(1):122-7. doi: 10.1111/j.1651-2227.2007.00029.x.

  PMID: 17187618 BACKGROUND

• Ries M, Clarke JT, Whybra C, Timmons M, Robinson C, Schlaggar BL, Pastores G, Lien YH, Kampmann C, Brady RO, Beck M, Schiffmann R. Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics. 2006 Sep;118(3):924-32. doi: 10.1542/peds.2005-2895.

  PMID: 16950982 BACKGROUND

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)

MeSH Terms

Conditions

Fabry Disease

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

Study Officials

• Arndt Rolfs, MD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2010
• First Posted: December 29, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 9, 2021

Record last verified: 2020-04

Locations

BE (1); GB (1); CR (1); DE (1); CZ (1); FR (1); AR (2); DK (1)