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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00140621

Enrollment

Registered

2005-09-01

Start date

2005-07-31

Completion date

2012-08-31

Last updated

2015-05-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fabry Disease

Keywords

cardiac fabry disease

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.

Interventions

DRUGAgalsidase beta

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 64 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156	Baseline 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 156	Baseline 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 156	Baseline to Week 156	Left ventricular mass was assessed by echocardiogram.
Change From Baseline in LVM at Week 156	Baseline to Week 156	Left ventricular mass was assessed by echocardiogram.

Secondary

Measure	Time frame	Description
Percent Change From Baseline in GL-3 Plasma Levels at Week 156	Baseline to Week 156	—
Change From Baseline in Short Form (36) Health Survey (SF-36) Scores at Week 156	Baseline 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).
Number of Participants in Overall Cardiac Function Assessment and Clinical Symptoms at Week 156: Change From Baseline in Cardiac Function Test	Baseline 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.

Countries

Japan

Participant flow

Recruitment details

The study was conducted at 7 centers between July 06, 2005 and August 6, 2012. One participant was treated at 2 study sites because the participant had to be transferred to another site during the study.

Participants by arm

Arm	Count
Agalsidase Beta Agalsidase beta 1 mg/kg intravenously once every 2 weeks up to 156 weeks.	6
Total	6

Baseline characteristics

Characteristic	Agalsidase Beta
Age, Continuous	53.8 years STANDARD_DEVIATION 5.7
Globotriaosylceramide (GL-3) Accumulation in the Myocardium No	0 participants
Globotriaosylceramide (GL-3) Accumulation in the Myocardium Not Measured	5 participants
Globotriaosylceramide (GL-3) Accumulation in the Myocardium Yes	1 participants
Height	156.63 centimeters (cm) STANDARD_DEVIATION 7.2
Left Ventricular Hypertrophy No	0 participants
Left Ventricular Hypertrophy Yes	6 participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	1 Participants
Weight	58.50 kilograms (kg) STANDARD_DEVIATION 9.24

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	6 / 6
serious Total, serious adverse events	1 / 6

Outcome results

Primary

Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156

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