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 April 2014 by Shire
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01298141
First received: February 15, 2011
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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: 180
Study Start Date: May 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Contacts
Contact: MedInfo Shire HGT +1-866-888-0660 US_ShireHGT_Medicalinformation@shire.com

Locations
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Aneal Khan, MD    (403)-955-7587    khaa@ucalgary.ca   
Principal Investigator: Aneal Khan, MD         
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2H7
Contact: Alicia Chan, MD    780-407-8314    alicia.chan@albertahealthservices.ca   
Principal Investigator: Alicia Chan, MD         
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Sandra Sirrs, MD    604-875-5965    sandra.sirrs@vch.ca   
Principal Investigator: Sandra Sirrs, MD         
Canada, Manitoba
Children's Hospital, Health Sciences Centre Winnipeg Recruiting
Winnipeg, Manitoba, Canada, R3A 1S1
Contact: Cheryl Rockman-Greenberg, MD    204-787-2441    cgreenberg@hsc.mb.ca   
Principal Investigator: Cheryl Rockman-Greenberg, MD         
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   
Principal Investigator: Michael West, MD         
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   
Principal Investigator: Sarah Dyack, MD         
Canada, Ontario
Kingston General Hospital Recruiting
Kingston, Ontario, Canada, K7L 3J6
Contact: Jennifer MacKenzie, MD    613-533-6310    jm36@post.queensu.ca   
Principal Investigator: Jennifer MacKenzie, MD         
London Health Sciences Centre - Victoria Hospital Recruiting
London, Ontario, Canada, N6C 2V5
Contact: Chitra Prasad, MD    519-685-8129    chitra.prasad@lhsc.on.ca   
Principal Investigator: Chitra Prasad, MD         
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   
Principal Investigator: Chantal Morel, MD         
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Chantal Morel, MD    416-586-4800 ext 4220    chantal.morel@uhn.on.ca   
Principal Investigator: Chantal Morel, MD         
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Joe TR Clarke, MD    416-813-5340    jtrc@sickkids.ca   
Principal Investigator: Joe TR Clarke, MD         
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   
Principal Investigator: Daniel Bichet, MD         
Centre Hospitalier Universitaire de Sherbrooke (CHUS) Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: Bruno Maranda, MD    819-564-5393    bruno.maranda@usherbrooke.ca   
Principal Investigator: Bruno Maranda, MD         
Sponsors and Collaborators
Shire
Investigators
Study Director: Arian Pano, MD, MPH Shire Human Genetic Therapies, Inc.
  More Information

No publications provided

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: April 22, 2014
Health Authority: Canada: Health Canada

Keywords provided by Shire:
agalsidase alfa
Replagal
Enzyme Replacement Therapy

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

ClinicalTrials.gov processed this record on August 19, 2014