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

Fabry Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140621
• Other study ID #: AGAL03204
• Status: Completed
• Phase: Phase 4
• First received: August 30, 2005
• Last updated: April 16, 2015
• Start date: July 2005
• Est. completion date: August 2012

Study information

• Verified date: April 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 64 Years

Eligibility

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 (a-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 a-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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Drug:
• Agalsidase beta

Locations

Country	Name	City	State
Japan	Fujita Health University Hospital	Aichi
Japan	Sapporo Medical University Hospital	Hokkaido
Japan	Akune Citizen Hospital	Kagoshima
Japan	Tohoku University Hospital	Miyagi
Japan	Nihon University Itabashi Hospital	Tokyo
Japan	Nihon University Nerima Hikarigaoka Hospital	Tokyo
Japan	Yamanashi Prefectural Central Hospital	Yamanashi

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent 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.	Baseline to Week 156	No
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.	Baseline to Week 156	No
Primary	Percent Change From Baseline in Left Ventricular Mass (LVM) at Week 156	Left ventricular mass was assessed by echocardiogram.	Baseline to Week 156	No
Primary	Change From Baseline in LVM at Week 156	Left ventricular mass was assessed by echocardiogram.	Baseline to Week 156	No
Secondary	Number of Participants in Overall Cardiac Function Assessment and Clinical Symptoms at Week 156: Change From Baseline in Cardiac Function Test	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.	Baseline to Week 156	No
Secondary	Percent Change From Baseline in GL-3 Plasma Levels at Week 156		Baseline to Week 156	No
Secondary	Change From Baseline in Short Form (36) Health Survey (SF-36) Scores at 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).	Baseline to Week 156	No