A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00140621
First received: August 30, 2005
Last updated: April 16, 2015
Last verified: April 2015
  Purpose

This is a multi-center, open label, phase IV study conducted to evaluate the efficacy and safety of agalsidase beta (Fabrazyme [recombinant form]) administered by intravenous drip infusion in participants with cardiac Fabry disease.

Participants participated for 4 weeks or less in the baseline period and 156 weeks for the treatment period.


Condition Intervention Phase
Fabry Disease
Drug: Agalsidase beta
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Open-label Study of the Safety and Efficacy of α-galactosidase A (R-h α-GAL) Replacement Therapy in Patients With Cardiac Fabry Disease

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156 [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
    Interventricular septum and left ventricular posterior wall thickness was assessed by echocardiogram.

  • Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156 [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
    Interventricular septum and left ventricular posterior wall thickness was assessed by echocardiogram.

  • Percent Change From Baseline in Left Ventricular Mass (LVM) at Week 156 [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
    Left ventricular mass was assessed by echocardiogram.

  • Change From Baseline in LVM at Week 156 [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
    Left ventricular mass was assessed by echocardiogram.


Secondary Outcome Measures:
  • Number of Participants in Overall Cardiac Function Assessment and Clinical Symptoms at Week 156: Change From Baseline in Cardiac Function Test [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
    Overall cardiac function assessment was assessed by tests (echocardiogram,cardiac catheterization (optional),electrocardiogram,B-type natriuretic peptide [BNP]), clinical symptoms (subjective symptoms) and the New York Heart Association (NYHA) cardiac functional classification.Overall assessment of cardiac function was assessed based on the evaluation items including interventricular septum thickness, left ventricular posterior wall thickness, left ventricular mass, clinical function tests and clinical symptoms. A subject was considered to be Improved: if Improved in 2 items or more, Unchanged: Improved in one item and unchanged in 2 items or unchanged in all 3 items, Aggravated: Aggravated in one item or more.

  • Percent Change From Baseline in GL-3 Plasma Levels at Week 156 [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
  • Change From Baseline in Short Form (36) Health Survey (SF-36) Scores at Week 156 [ Time Frame: Baseline to Week 156 ] [ Designated as safety issue: No ]
    The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical component score (PCS) and mental component score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).


Enrollment: 6
Study Start Date: July 2005
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Agalsidase Beta
Agalsidase beta 1 milligram per kilogram (mg/kg) intravenously once every 2 weeks up to 156 weeks.
Drug: Agalsidase beta
Other Name: Fabrazyme®

  Eligibility

Ages Eligible for Study:   20 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants definitively diagnosed with cardiac Fabry disease (who fulfill all of the following criteria)

    • In the case of male participants, documented plasma or leukocyte alpha-galactosidase A (α-GAL) activity was no more than 20 percent (%) of normal value (except for heterozygous female participants)
    • Left ventricular hypertrophy was noted.
    • Accumulation of globotriaosylceramide (GL-3) in the myocardium or a genetic deficiency associated with α-GAL was confirmed
    • Or in the case of heterozygous female participants, when the family (father or son) was diagnosed with Fabry disease. (Father or son was related by birth.)
    • Without symptoms or signs of Fabry, such as acroparesthesia, angiokeratomas, abnormal sweating, pain of distal extremities, chronic abdominal pain/diarrhea and corneal opacities were observed, except for proteinuria sign.
  • Participants with interventricular and posterior wall thickness of at least 13 millimeter (mm) on echocardiography within 3 months before signed date to informed consent
  • Participants in whom cardiac function was rated as Class I or II according to the New York Heart Association (NYHA) classification when giving informed consent.
  • Participants classification: inpatients and outpatients
  • Participants who had given written informed consent before the study-related baseline tests.

Exclusion Criteria:

  • Participants with severe hypertension (for example, blood pressure more than or equal to 180 millimeter of mercury [mmHg] and/or blood pressure more than or equal to 110 mmHg in spite of adequate medication)
  • Participants whose serum creatinine level was higher than the upper normal limit within 3 months (12 weeks) prior to giving informed consent.
  • Participants who had undergone kidney transplantation or were currently on dialysis.
  • Participants with any serious hepatic disorder. Participants who had abnormal hepatic function test values within 3 months (12 weeks) prior to giving informed consent (when either alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level exceeded the value five times as high as the upper normal limit).
  • Permanent pacemaker or defibrillator implanted participants
  • Pregnant or lactating women
  • Participants who had taken this drug for 6 months (26 weeks) or more before giving informed consent.
  • Participants who had participated in a clinical study employing any other investigational product within 3 months prior to giving informed consent.
  • Enzyme replacement therapy history, except for agalsidase beta
  • Participants who were unwilling to comply with the requirements of the protocol.
  • Others judged by the investigator or sub-investigator to be ineligible for the study
  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: NCT00140621

Locations
Japan
Fujita Health University Hospital
Aichi, Japan, 470-1192
Sapporo Medical University Hospital
Hokkaido, Japan, 060-8543
Akune Citizen Hospital
Kagoshima, Japan, 899-1611
Tohoku University Hospital
Miyagi, Japan, 980-8574
Nihon University Itabashi Hospital
Tokyo, Japan, 173-8610
Nihon University Nerima Hikarigaoka Hospital
Tokyo, Japan, 179-0072
Yamanashi Prefectural Central Hospital
Yamanashi, Japan, 400-8506
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00140621     History of Changes
Other Study ID Numbers: AGAL03204
Study First Received: August 30, 2005
Results First Received: April 1, 2015
Last Updated: April 16, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Sanofi:
cardiac fabry disease

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
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sphingolipidoses
Vascular Diseases

ClinicalTrials.gov processed this record on August 27, 2015