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

Phase 4
Completed
Conditions
Fabry Disease
Interventions
Registration Number
NCT00140621
Lead Sponsor
Genzyme, a Sanofi Company
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
6
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Agalsidase BetaAgalsidase betaAgalsidase beta 1 milligram per kilogram (mg/kg) intravenously once every 2 weeks up to 156 weeks.
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156Baseline to Week 156

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 156Baseline to Week 156

Interventricular septum and left ventricular posterior wall thickness was assessed by echocardiogram.

Percent Change From Baseline in Left Ventricular Mass (LVM) at Week 156Baseline to Week 156

Left ventricular mass was assessed by echocardiogram.

Change From Baseline in LVM at Week 156Baseline to Week 156

Left ventricular mass was assessed by echocardiogram.

Secondary Outcome Measures
NameTimeMethod
Number of Participants in Overall Cardiac Function Assessment and Clinical Symptoms at Week 156: Change From Baseline in Cardiac Function TestBaseline to Week 156

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 156Baseline to Week 156
Change From Baseline in Short Form (36) Health Survey (SF-36) Scores at Week 156Baseline to Week 156

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).

Trial Locations

Locations (7)

Fujita Health University Hospital

🇯🇵

Aichi, Japan

Sapporo Medical University Hospital

🇯🇵

Hokkaido, Japan

Tohoku University Hospital

🇯🇵

Miyagi, Japan

Akune Citizen Hospital

🇯🇵

Kagoshima, Japan

Nihon University Itabashi Hospital

🇯🇵

Tokyo, Japan

Yamanashi Prefectural Central Hospital

🇯🇵

Yamanashi, Japan

Nihon University Nerima Hikarigaoka Hospital

🇯🇵

Tokyo, Japan

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