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

Condition(s) targeted: Fabry Disease

Intervention: Agalsidase beta (Fabrazyme) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Genzyme

Official(s) and/or principal investigator(s):
Bernard Bénichou, M.D., Ph.D., Study Director, Affiliation: Genzyme

Overall contact:
Clinical Division Genzyme K.K., Phone: 81-3-3230-8285

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:

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 (optional), electrocardiogram, brain natriuretic peptide [BNP]), clinical symptoms (subjective symptoms) and the New York Heart Association (NYHA) cardiac functional classification

2. The mean change and changes in plasma globotriaosylceramide (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 magnetic resonance imaging (MRI), clinical laboratory data, and immunogenicity will also be explored.

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

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome:

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 outcome:

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

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

Minimum age: 20 Years. Maximum age: 64 Years. Gender(s): 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)

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

Clinical Division Genzyme K.K., Phone: 81-3-3230-8285

Kagoshima University Hospital, Kagoshima 890-8520, Japan; Recruiting
Shuichi Hamasaki, M.D., Ph.D., Principal Investigator

Uwajima City Hospital, Ehime 798-8510, Japan; Recruiting
Mareomi Hamada, M.D., Ph.D., Principal Investigator

Fujita Health University Hospital, Aichi 470-1192, Japan; Recruiting
Shin-ichiro Morimoto, M.D., Ph.D., Principal Investigator

Yamanashi Prefectural central Hospital, Yamanashi 400-8506, Japan; Recruiting
Kazunori Aizawa, M.D., Ph.D., Principal Investigator

Tohoku University Hospital, Miyagi 980-8574, Japan; Recruiting
Hiroaki Shimokawa, M.D., Ph.D., Principal Investigator

US FDA Approved Full Prescribing Information for Fabrazyme®

Starting date: May 2005
Ending date: March 2011
Last updated: April 3, 2008