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

Patients will participate for 4 weeks or less in the baseline period and 156 weeks for the treatment period.

Primary evaluation variables that will be explored:

1. Changes in interventricular septum and left ventricular posterior wall thickness from baseline until Week 156 or discontinuation of treatment as assessed by echocardiogram.
2. Changes in left ventricular mass (LVM) from baseline until Week 156 or discontinuation of treatment as assessed by echocardiogram.

Secondary evaluation variables that will be explored:

1. Results of overall evaluation of cardiac function assessed by cardiac function tests (echocardiogram, cardiac catheterization, electrocardiogram, BNP), clinical symptoms (subjective symptoms) and the NYHA cardiac functional classification
2. The mean change and changes in plasma GL-3 levels
3. Changes in GL-3 accumulation scores in myocardial tissue from baseline until Week 156 or discontinuation of treatment as assessed by light microscopy
4. Changes in SF-36 Health Survey scores
5. Safety evaluation Adverse events, vital signs, head MRI, clinical laboratory data, immunogenicity

Condition	Intervention	Phase
cardiac fabry disease	Drug: Agalsidase beta (recombinant form)	Phase IV

Further Study Details: 

Primary Outcomes: - To evaluate the efficacy of Fabrazyme in reducing interventricular septum and left ventricular posterior wall thickness assessed by echocardiogram; - To evaluate the efficacy of Fabrazyme in reducing left ventricular mass (LVM) assessed by echocardiogram.
Secondary Outcomes: - To make an overall evaluation of changes in cardiac function assessment by cardiac function tests (echocardiogram, cardiac catheterization, electrocardiogram, BNP), clinical symptoms (subjective symptoms) and the NYHA cardiac functional classification.; - To evaluate the efficacy of this drug in lowering plasma globotriaosylceramide (hereinafter referred to as GL-3) level.; - To evaluate in evaluable subjects the efficacy of this drug in reducing GL-3 accumulation in myocardial tissue.; - To evaluate the efficacy of this drug according to SF-36 Health Survey scores.; - To evaluate the safety of this drug.
Expected Total Enrollment:  10

Ages Eligible for Study:  20 Years   -   64 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

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

• In the case of male patients, documented plasma or leukocyte a- GAL activity is no more than 20% of normal value. (except for heterozygous female patients) • Left Ventricular hypertrophy is noted. • Accumulation of GL-3 in the myocardium or a genetic deficiency associated with a-GAL has been confirmed. Or in the case of heterozygous female patients, when the family (father or son) diagnosed Fabry disease. (Father or son is 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 are observed, except for proteinuria sign.

• Patient with interventricular and posterior wall thickness of at least 13mm on echocardiography within 3 months before signed date to informed consent
• Patients in whom cardiac function is rated as Class I or II according to the NYHA classification when giving informed consent.
• Age: between 20 years and 64 years
• Sex: males and females
• Patient classification: inpatients and outpatients
• Patients who have given written informed consent before the study-related baseline tests.

Exclusion Criteria:

• Patient with severe hypertension (e. g, systolic blood pressure 180 mmHg and/or diastolic blood pressure 110 mmHg in spite of adequate medication)
• Patients whose serum creatinine level is higher than the upper normal limit within 3 months (12 weeks) prior to giving informed consent.
• Patients who have undergone kidney transplantation or are currently on dialysis.
• Patients with any serious hepatic disorder. Patients who have abnormal hepatic function test values within 3 months (12 weeks) prior to giving informed consent (when either ALT or AST level exceeds the value five times as high as the upper normal limit).
• Permanent pacemaker or defibrillator implanted patients
• Pregnant or lactating women
• Patients who have taken this drug for 6 months (26 weeks) or more before giving informed consent.
• Patients who have participated in a clinical study employing any other investigational product within 3 months prior to giving informed consent.
• Enzyme replacement therapy history, except for Fabrazyme.
• Patients who are unwilling to comply with the requirements of the protocol.
• Others judged by the investigator or subinvestigator to be ineligible for the study

Please refer to this study by ClinicalTrials.gov identifier  NCT00140621

Clinical Affairs      81-3-3230-8285 

Japan
      Kagoshima University Hospital, Kagoshima,  890-8520,  Japan; Recruiting
      Umajima City Hospital, Ehime,  798-8510,  Japan; Recruiting

Study chairs or principal investigators

Kazuyuki Hatakeyama, M.D., Ph.D.,  Study Director,  Genzyme Corporation (Genzyme Japan K.K.)   

Study ID Numbers:  AGAL03204
Last Updated:  August 31, 2005
Record first received:  August 30, 2005
ClinicalTrials.gov Identifier:  NCT00140621
Health Authority: Japan: Ministry of Health, Labor and Welfare
ClinicalTrials.gov processed this record on 2005-09-06