A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Shire
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: February 15, 2011
Last updated: May 6, 2016
Last verified: May 2016
The purpose of this study is to observe the safety of agalsidase alfa in Canadian patients with Fabry disease.

Condition Intervention Phase
Fabry Disease
Biological: agalsidase alfa
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal® (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease

Resource links provided by NLM:

Further study details as provided by Shire:

Primary Outcome Measures:
  • The objective of this study is to observe the safety of Replagal in Canadian patients with Fabry disease. [ Time Frame: Baseline to EOS ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: May 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Replagal®
All eligible patients may receive Replagal produced by the bioreactor process (AF Replagal) on this treatment plan until AF Replagal is commercially available for the patient, the patient's participation is discontinued, or the study is discontinued, whichever comes first.
Biological: agalsidase alfa

Cohort 1: 0.2 mg/kg body weight administered as an intravenous (IV) infusion over 40 minutes every other week (EOW)

Cohort 2: 0.2 mg/kg body weight administered as an intravenous (IV) infusion over 40 minutes weekly

Other Name: Replagal

Detailed Description:

This study will evaluate the safety of agalsidase alfa in patients with Fabry disease.

Patients diagnosed with Fabry disease who meet current Canadian guidelines for enzyme replacement therapy will be eligible to enroll in the study and will receive agalsidase alfa at a dose of 0.2 mg/kg body weight administered by an IV infusion over 40 minutes every week or every other week, based on previous treatment.

Shire has implemented a change to the drug substance manufacturing process. Safety data will be collected in patients receiving product manufactured with this process. There are no changes to the drug product formulation, manufacturing site, manufacturing process, and container closure.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Cohort 1:

  1. The patient has a documented diagnosis of Fabry disease.
  2. The patient is sufficiently compliant with study activities to participate in this treatment plan, as judged by the Investigator.
  3. The patient must meet current Canadian guidelines for enzyme replacement therapy for Fabry disease by meeting one of the following criteria:

    1. Age-adjusted glomerular filtration rate (GFR) <80 ml/min or a decline in GFR of >10% which is sustained for 3 months and for which other causes of declining renal function have been excluded by a nephrologist or any 2 of the following:

      • Isolated proteinuria ≥500 mg/day/1.73 m2 without other cause
      • Nephrogenic diabetes insipidus
      • Fanconi syndrome
      • Hypertension
    2. Evidence of cardiac involvement related to Fabry disease including any 2 of the following:

      • Left ventricular (LV) wall thickness >12 mm
      • Left ventricular hypertrophy (LVH) by electrocardiogram (ECG); Estes ECG score must be >5
      • Left ventricular mass index (LVMI) by 2D echocardiogram 20% above normal for age
      • Diastolic filling abnormalities by 2D echocardiogram or by other accepted measures of diastolic filling. E/A ration >2.0 and deceleration time <140 msec
      • Increase of LV mass of at least 5 g/m2/year, with three measurements over a minimum of 12 months
      • Increase of left atrium (LA) size on 2D echo at least 10% above normal for age. In parasternal long axis view (PLAX) >33 mm; in four chamber view >42 mm
      • Cardiac conduction and rhythm abnormalities: atrioventricular (AV) block, short PR interval, left branch bundle block (LBBB), ventricular or atrial tachyarrhythmias, sinus bradycardia (in the absence of drugs with negative chronotropic activity)
      • Delayed posterolateral left ventricular wall late enhancement on MRI as evidence of advanced cardiac disease with fibrosis
    3. Evidence of neurological involvement related to Fabry disease including 1 of the following:

      • Stroke or transient ischemic attack (TIA) prior to the age of 55 documented by a neurologist
      • Acute onset unilateral hearing loss
      • Acut monocular visual loss without other cause
    4. Chronic, intractable diarrhea and/or abdominal pain/cramps, refractory to standard management for at least 6 months.
    5. Chronic, intractable neuropathic pain, refractory to analgesics and standard pain management for at least 6 months.

    Cohort 2:

  4. Patient must have participated in Study REP001a.

Exclusion Criteria:

  1. The patient has experienced an anaphylactic or anaphylactoid reaction or other infusion-related reaction which, in the opinion of the Investigator, precludes further treatment with agalsidase alfa or may interfere with the interpretation of the study.
  2. The patient is otherwise unsuitable for the study, in the opinion of the Investigator.
  3. The patient is enrolled in another clinical study, other than the Canadian Fabry Disease Initiative (CFDI).
  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: NCT01298141

Contact: Shire Contact clinicaltransparency@shire.com

Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Aneal Khan, MD    (403)-955-7587    khaa@ucalgary.ca   
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2H7
Contact: LeeAnn Langkass    514-338-2222 # 3110    c-fortier@crhsc.rtss.qc.ca   
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Sandra Sirrs, MD    604-875-5965    sandra.sirrs@vch.ca   
Canada, Manitoba
University of Manjtoba Recruiting
Winnipeg, Manitoba, Canada, R3A 1S1
Contact: Catherine Desrochers    204-787-4014    CDESROCHERS3@EXCHANGE.HSC.MB.CA   
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 1V8
Contact: Michael West, MD    902-473-4023    mlwest@dal.ca   
Izaak Walton Killam (IWK) Health Centre Recruiting
Halifax, Nova Scotia, Canada, B3K 6R8
Contact: Sarah Dyack, MD    902-470-8754    sarah.dyack@iwk.nshealth.ca   
Canada, Ontario
Kingston General Hospital Recruiting
Kingston, Ontario, Canada, K7L 3J6
Contact: Jennifer MacKenzie, MD    613-533-6310    jm36@post.queensu.ca   
London Health Sciences Centre - Victoria Hospital Recruiting
London, Ontario, Canada, N6C 2V5
Contact: Nicholas Watkins    519-685-8500 ext. 53510    NICHOLAS.WATKINS@LHSC.ON.CA   
The Hospital for Sick Children Completed
Toronto, Ontario, Canada, M5G 1X8
The Fred A. Litwin Family Centre in Genetic Medicine, Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5T 3L9
Contact: Chantal Morel, MD    416-586-4800 ext 4220    chantal.morel@uhn.on.ca   
Canada, Quebec
Hopital du Sacre-Coeur de Montreal Recruiting
Montreal, Quebec, Canada, H4J 1C5
Contact: Daniel Bichet, MD    514-338-2222 ext 2173    daniel.bichet@umontreal.ca   
Centre Hospitalier Universitaire de Sherbrooke (CHUS) Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: Bruno Maranda, MD    819-564-5393    bruno.maranda@usherbrooke.ca   
Sponsors and Collaborators
Study Director: Shire Physician Shire
  More Information

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01298141     History of Changes
Other Study ID Numbers: HGT-REP-081 
Study First Received: February 15, 2011
Last Updated: May 6, 2016
Health Authority: Canada: Health Canada

Keywords provided by Shire:
Enzyme Replacement Therapy
agalsidase alfa

Additional relevant MeSH terms:
Fabry Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on May 30, 2016