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

Sponsor:	Genzyme
Information provided by:	Genzyme
ClinicalTrials.gov Identifier:	NCT00140621

Purpose

This is a 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:

Changes in interventricular septum and left ventricular posterior wall thickness from baseline until Week 156 or discontinuation of treatment as assessed by echocardiogram.
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:

Results of overall evaluation of cardiac function assessed by cardiac function tests (echocardiogram, cardiac catheterization (optional), electrocardiogram, brain natriuretic peptide [BNP]), clinical symptoms (subjective symptoms) and the New York Heart Association (NYHA) cardiac functional classification
The mean change and changes in plasma globotriaosylceramide (GL-3) levels
Changes in GL-3 accumulation scores in myocardial tissue from baseline until Week 156 or discontinuation of treatment as assessed by light microscopy
Changes in SF-36 Health Survey scores
Safety evaluation

Adverse events, vital signs, head magnetic resonance imaging (MRI), clinical laboratory data, and immunogenicity will also be explored.

Condition	Intervention	Phase
Fabry Disease	Drug: Agalsidase beta (Fabrazyme)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Multicenter Open-label Study of the Safety and Efficacy of A-galactosidase A (R-h a-GAL) Replacement Therapy in Patients With Cardiac Fabry Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Fabry disease Farber lipogranulomatosis primary carnitine deficiency succinic semialdehyde dehydrogenase deficiency

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

To evaluate the efficacy of Fabrazyme in reducing interventricular septum and left ventricular posterior wall thickness assessed by echocardiogram [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
To evaluate the efficacy of Fabrazyme in reducing left ventricular mass (LVM) assessed by echocardiogram [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Results of overall evaluation of changes in cardiac function assessed by tests (echocardiogram,cardiac catheterization(optional),electrocardiogram,BNP), clinical symptoms(subjective symptoms) and the NYHA cardiac functional classification [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
To evaluate in evaluable subjects the efficacy of this drug in reducing GL-3 accumulation in myocardial tissue [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
To evaluate the efficacy of this drug according to SF-36 Health Survey scores [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: No ]
To evaluate the safety of this drug [ Time Frame: Up to 156 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	6
Study Start Date:	July 2005
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Fabrazyme 1.0 mg/kg body weight infused every 2 weeks as an intravenous infusion.

Eligibility

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

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) is diagnosed with 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 13 mm 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.
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 sub-investigator to be ineligible for the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00140621

Locations

Japan
Kagoshima University Hospital
Kagoshima, Japan, 890-8520
Uwajima City Hospital
Ehime, Japan, 798-8510
Fujita Health University Hospital
Aichi, Japan, 470-1192
Yamanashi Prefectural central Hospital
Yamanashi, Japan, 400-8506
Tohoku University Hospital
Miyagi, Japan, 980-8574

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided

Responsible Party:	Genzyme Coporation ( Medical Monitor )
Study ID Numbers:	AGAL03204
Study First Received:	August 30, 2005
Last Updated:	September 29, 2009
ClinicalTrials.gov Identifier:	NCT00140621 History of Changes
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Genzyme:

cardiac fabry disease

Additional relevant MeSH terms:

Lipid Metabolism, Inborn Errors
Sphingolipidoses
Metabolic Diseases
Lysosomal Storage Diseases, Nervous System
Lysosomal Storage Diseases
Nervous System Diseases
Central Nervous System Diseases
Brain Diseases

Metabolism, Inborn Errors
Genetic Diseases, Inborn
Fabry Disease
Genetic Diseases, X-Linked
Brain Diseases, Metabolic, Inborn
Lipidoses
Lipid Metabolism Disorders
Brain Diseases, Metabolic

ClinicalTrials.gov processed this record on February 08, 2010