Canadian Fabry Disease Initiative (CFDI) Enzyme Replacement Therapy (ERT) Study

This study is currently recruiting participants.
Verified January 2009 by Canadian Fabry Research Consortium
Sponsor:
Collaborators:
University Health Network, Toronto
Capital District Health Authority, Canada
Information provided by:
Canadian Fabry Research Consortium
ClinicalTrials.gov Identifier:
NCT00455104
First received: March 30, 2007
Last updated: January 28, 2009
Last verified: January 2009
  Purpose

CFDI STUDY with ENZYME REPLACE THERAPY (ERT): Canada-Wide Patient Recruitment

Fabry disease is a rare, inherited, genetic condition due to a deficiency of an enzyme called alpha-galactosidase A. This enzyme deficiency causes the small blood vessels to accumulate a substance called glycolipid. Without sufficient levels of the enzyme, alpha-galactosidase A, persons with Fabry Disease develop severe neuropathic pain, kidney disease, heart disease, stroke and/or premature death; often before the age of 60 years old.

Fabry Disease is estimated to affect approximately one out of every 40,000 males and up to twice as many females in Canada. We know there are approximately 225 people living in Canada with Fabry disease, with the largest number living in Nova Scotia. However, we do not have the exact number of persons in Canada who have this disease. A common problem in studying rare conditions is the difficulty in identifying the majority of people suffering from such a disease. Gathering their health information in order to better understand the natural disease progression and its response to treatment is difficult.

Until recently, treating symptoms was all that was available for people with Fabry Disease. In 2001, enzyme replacement therapy (ERT) was developed as a treatment for this rare condition. ERT provides the deficient enzyme and may be beneficial in Fabry Disease. The Canadian Fabry Disease Initiative (CFDI) will determine the impact of Enzyme Replacement Therapy (ERT) on the development of complications of Fabry Disease in males and females currently on, or who have received ERT; and to assess which of these complications respond to the ERT therapy. Another purpose of this study is to establish a national registry which will collect information on all persons with Fabry Disease in Canada.

Early ERT studies involving humans had small numbers of subjects and the studies were of short duration. The results of these clinical studies did lead to approval of the therapy in many countries around the world including Canada. To date though, evidence of the usefulness of ERT and its direct impact on the natural course of Fabry disease has been limited, while its cost continues to be very high. As a result of these issues, there will need to be continued and long-term collection of information related to the effectiveness of ERT to better document its true clinical outcomes in Canadian people with Fabry disease.

The 5 goals of this nation-wide study are as follows:

  1. To establish a national registry which will collect information related to the identification and monitoring of all persons with Fabry disease in Canada;
  2. To determine the degree to which existing complications of Fabry disease respond or fail to respond to ERT;
  3. To determine the impact of ERT on the development of complications of Fabry disease in men and women who are on ERT or whose ERT was interrupted;
  4. To identify which of these clinical problems can best predict the outcome of ERT on Fabry disease.
  5. To identify possible side effects of ERT.

Condition Intervention Phase
Fabry Disease
Drug: agalsidase alfa (Replagal®) and agalsidase beta (Fabrazyme®)
Drug: Enzyme Replacement Therapy (ERT)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Enzyme Replacement Therapy for Fabry Disease: A Model for the Integration of Rare Disease Therapeutics Into the Canadian Health Care System

Resource links provided by NLM:


Further study details as provided by Canadian Fabry Research Consortium:

Primary Outcome Measures:
  • (1) To determine the degree to which existing complications of Fabry disease respond or fail to respond to ERT; [ Time Frame: 2017 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • (2) To establish a national registry which will collect information related to the identification and monitoring of all persons with Fabry disease in Canada; [ Time Frame: 2017 ] [ Designated as safety issue: No ]
  • 3) To determine the impact of ERT on the development of complications of Fabry disease in men and women who are on ERT or whose ERT was interrupted; [ Time Frame: 2017 ] [ Designated as safety issue: Yes ]
  • 4) To identify which of these clinical problems can best predict the outcome of ERT on Fabry disease. [ Time Frame: 2017 ] [ Designated as safety issue: Yes ]
  • 5) To identify possible side effects of ERT [ Time Frame: 2017 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 250
Study Start Date: January 2007
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cohort 1A
Cohort 1A are Fabry Disease subjects who are currently on enzyme replacement therapy (ERT) or have had ERT interrupted and will continue the same ERT drug as before. Estimated total of 50 Cohort 1A subjects.
Drug: agalsidase alfa (Replagal®) and agalsidase beta (Fabrazyme®)

agalsidase beta (Fabrazyme®)1 mg/kg IV Q2weeks

agalsidase alfa (Replagal®)

  • standard dose: 0.2 mg/kg or 0.4 mg/kg IV Q2weeks
  • higher dose (REP001A sub-study for renal and/or cardiac decline despite six months of standard doses of Replagal): 0.2 mg/kg or 0.4 mg/kg IV weekly
Drug: Enzyme Replacement Therapy (ERT)
agalsidase alpha (Replagal) or agalsidase beta (Fabrazyme)
Active Comparator: Cohort 1B
Cohort 1B subjects have Fabry Disease and have never received ERT, but now meet the Canadian Fabry Guidelines to initiate ERT. An estimated 100 Cohort 1B subjects will be enrolled in Canada.
Drug: agalsidase alfa (Replagal®) and agalsidase beta (Fabrazyme®)

agalsidase beta (Fabrazyme®)1 mg/kg IV Q2weeks

agalsidase alfa (Replagal®)

  • standard dose: 0.2 mg/kg or 0.4 mg/kg IV Q2weeks
  • higher dose (REP001A sub-study for renal and/or cardiac decline despite six months of standard doses of Replagal): 0.2 mg/kg or 0.4 mg/kg IV weekly
No Intervention: Natural Cohort

Detailed Description:

CFDI STUDY with ENZYME REPLACE THERAPY (ERT): Canada-Wide Patient Recruitment

There are approximately 250 people in Canada known to have Fabry Disease For more details about Fabry Disease, please refer to the "Brief Summary." The Canadian Fabry Disease Initiative will collect information from 3 different study groups of Fabry subjects recruited from across Canada over a 10-year period.

The 5 goals of this nation-wide study are as follows:

  1. To establish a national registry which will collect information related to the identification and monitoring of all persons with Fabry disease in Canada;
  2. To determine the degree to which existing complications of Fabry disease respond or fail to respond to ERT;
  3. To determine the impact of ERT on the development of complications of Fabry disease in men and women who are on ERT or whose ERT was interrupted;
  4. To identify which of these clinical problems can best predict the outcome of ERT on Fabry disease.
  5. To identify possible side effects of ERT.

This 3-armed study will consist of 3 study populations. The first group will be referred to as Cohort 1A. This group includes males and females with Fabry Disease, who are currently on ERT or have had ERT treatment interrupted. We are expecting approximately 50 persons in Cohort 1A in total.

The second group, Cohort 1B, will consist of people who have never had ERT, but who now meet the current Canadian guidelines for starting ERT therapy. Approximately 100 subjects will be recruited in Canada.

The third group will be called the Natural History Cohort with approximately 100 Canadian subjects with mild Fabry Disease who currently do not need ERT. For BC, we anticipate recruiting 15 subjects for the Natural History Cohort group. All these numbers are estimates because the exact number of people in Canada with Fabry Disease is unknown at this time.

Data will be collected at baseline and every 6 months for 3 years, as follows:

  • Medical History
  • Physical examination
  • Neurological exam
  • Eye exam
  • Electrocardiogram (ECG) - an electrical tracing of one's heart rhythm
  • Echocardiogram (ultrasound of the heart)
  • Holter monitor
  • Audiogram
  • Magnetic Resonance Imaging (MRI) or CT Scan of the head
  • Pain Questionnaire and a Quality of Life Questionnaire
  • Lab tests (including alpha-galactosidase levels)
  • Review of current medications
  • 24-hour urine collection or a random spot urine test

To date though, evidence of the usefulness of ERT and its direct impact on the natural course of Fabry disease has been limited, while its cost continues to be very high (approximately $300,000 CDN per year per patient). As a result of these issues, there will need to be continued and long-term collection of information related to the effectiveness of ERT to better document its true clinical outcomes in Canadian people with Fabry disease.

  Eligibility

Ages Eligible for Study:   5 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

(A) ALL of the following criteria must be met for each CFDI subject in Cohort 1A, Cohort 1B & the Natural History Cohort:

  • Age 5 years and older, up to & including age 85 years; and
  • Able to give informed consent; and
  • A clinical diagnosis of Fabry disease; and
  • Compliance with all the clinic visits, questionnaires, interviews and assessments during the study period; and
  • A Canadian citizen or a landed immigrant For Cohort 1A and Cohort 1B, each subject must also be able to tolerate Enzyme Replacement Therapy (ERT)

(B) ALL of the following criteria must be met for each REP001A subject originally enroled as a CFDI Cohort 1A or Cohort 1B subject:

  • Age 5-85 years old; and
  • Able to give informed consent; and
  • A clinical diagnosis of Fabry disease; and
  • Willing to comply with all the clinic visits, questionnaires, interviews and assessments during the study period; and
  • A Canadian citizen or a landed immigrant; and
  • Receiving agalsidase alfa (Replagal®) standard doses (0.2 mg/kg every 2 weeks) for a minimum of 6 consecutive months; and
  • Evidence of declining kidney and/or heart function while on Replagal®, as shown by laboratory and/or imaging results; and
  • Currently enrolled in the CFDI study.

EXCLUSION CRITERIA:

  • Intolerance to ERT, such as a serious drug reaction; or
  • Enrolment in another clinical study in the last 30 days; or
  • Problem complying with all the clinic visits, questionnaires, interviews and assessments during the study period; or
  • An estimated life expectancy of less than 12 months; and
  • For REP001A (high dose Replagal sub-study): worsening of kidney and/or heart function (as shown by laboratory and/or imaging results) due to another underlying medical condition (i.e. not related to Fabry Disease)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00455104

Contacts
Contact: Michael L. West, MD 902-473-4032 mlwest@dal.ca
Contact: Kaye Le Moine, RN 902-473-5770 klemoine@dal.ca

Locations
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T2T 5C7
Contact: Robin Casey, MD    403-943-7587    robin.casey@crha-health.ab.ca   
Contact: Colleen McNeil    403-955-7941    colleen.mcneil@calgaryhealthregion.ca   
Principal Investigator: Robin Casey, MD         
Canada, British Columbia
Vancouver General Hospital Adult Metabolic Diseases Clinic Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Sandra Sirrs, MD    604-875-5965    sandra.sirrs@vch.ca   
Contact: Wendy A Leong, PharmD    604-680-4355    wendy@leong.com   
Principal Investigator: Sandra Sirrs, MD, FRCPC         
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 1V8
Contact: Michael L West, MD    902-473-4032    mlwest@dal.ca   
Contact: Susan Hyndman, RN    902-473-7083    susan.hyndman@cdha.nshealth.ca   
Principal Investigator: Michael L West, MD         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Joe T. Clarke, MD, FRCP(C)    416-813-5340    jtrc@sickkids.on.ca   
Contact: Tracy Heeney, BSc, CCRP    416-586-4800 ext 4220    tracy.heeney@uhn.on.ca   
Principal Investigator: Joe Clarke, MD         
Canada, Quebec
University of Montreal, Department of Medicine Recruiting
Montreal, Quebec, Canada
Contact: Daniel Bichet, MD    514-338-2222 ext 2173    daniel.bichet@umontreal.ca   
Contact: Carole Fortier, RN    514-338-2216    c-fortier@crhsc.rtss.qc.ca   
Principal Investigator: Daniel Bichet, MD         
Sponsors and Collaborators
Canadian Fabry Research Consortium
University Health Network, Toronto
Capital District Health Authority, Canada
Investigators
Principal Investigator: Michael L West, MD Queen Elizabeth II Health Sciences Centre (Capital District Health Authority), Halifax, Nova Scotia, Canada
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Michael West, Canadian Fabry Research Consortium
ClinicalTrials.gov Identifier: NCT00455104     History of Changes
Other Study ID Numbers: CFDI 001, REP001A (Replagal) Sub Study
Study First Received: March 30, 2007
Last Updated: January 28, 2009
Health Authority: Health Canada: Ministry of Health & Long Term Care, Ontario

Keywords provided by Canadian Fabry Research Consortium:
Fabry Disease
Enzyme Replacement Therapy (ERT)

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
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 April 17, 2014