Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease - Full Text View

Sponsor:	Shire Human Genetic Therapies, Inc.
Information provided by:	Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:	NCT00864851

Purpose

The purpose of this study is to compare the safety and effectiveness of various doses of Replagal in patients with cardiomyopathy due to Fabry disease.

Condition	Intervention	Phase
Fabry Disease	Biological: Replagal	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Multi-Center, Open-Label, Randomized Study Evaluating the Safety and Efficacy of Three Dosing Regimens of Replagal Enzyme Replacement Therapy in Adult Patients With 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

Drug Information available for: Agalsidase alfa alpha-Galactosidase

U.S. FDA Resources

Further study details as provided by Shire Human Genetic Therapies, Inc.:

Primary Outcome Measures:

To compare the effects of several dosing regimens of Replagal on cardiac structure and function. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To compare the effects of several dosing regimens of Replagal on exercise tolerance. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	43
Study Start Date:	December 2008
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Replagal every two weeks: Active Comparator	Biological: Replagal Comparison of different dosing regimens Biological: Replagal Replagal IV , comparison of doses
Replagal every week: Active Comparator	Biological: Replagal Comparison of different dosing regimens Biological: Replagal Replagal IV , comparison of doses
Replagal every week: Active Comparator	Biological: Replagal Comparison of different dosing regimens Biological: Replagal Replagal IV , comparison of doses

Detailed Description:

Fabry disease is an inherited, metabolic disease caused by mutations in the GALA gene. Patients with Fabry disease accumulate a complex glycosphingolipid named globotriaosylceramide (Gb3) in various tissues and organs. All organs are affected in Fabry disease but the majority of the morbidity and mortality are caused by cardiac, renal and neurological dysfunction. Accumulation of Gb3 in the heart causes hypertrophic cardiomyopathy, valvular abnormalities, arrhythmias and infarctions. Replagal has been shown to reduce Gb3 from key tissues and organs, and stabilize renal function in patients with Fabry disease. Evidence suggests that Replagal reduces left ventricular mass (LVM) and improves maximal fractional shortening (MFS)of the heart. Left ventricular hypertrophy is a major cause of morbidity and mortality in patients with Fabry disease.

This is a study of the safety and effectiveness of 3 dosing regimens of Replagal in adult patients with left ventricular hypertrophy due to Fabry disease.

The primary objective of the study will be assessed by comparing 2 dosing regimens of Replagal on reduction of left ventricular mass measured by echocardiography.

The secondary objectives of this study will be assessed by comparing 2 dosing regimens of Replagal on each of the following: exercise tolerance using 2 standard exercise tests; improvement in disease quality of life in heart failure patients; improvement of heart failure symptoms; Standard Safety measurement (i.e.adverse experiences, vital signs, physical exam and laboratory tests).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

>18 years-old;
Male:Fabry disease confirmed by deficiency of alfa galactosidase A activity OR Female:Fabry disease confirmed by a mutation of the alfa galactosidase A gene;
ERT-naïve;
LVM/h > 50g/m2.7 for males and >47 g/m2.7 for females;
Negative pregnancy test at enrollment and contraception use required throughout study for female patients;
Signed informed consent;

Exclusion Criteria:

Class IV heart failure;
Clinically significant hypertension;
Hemodynamically significant valvular stenosis or regurgitation;
Morbid obesity;
Known autosomal dominant sarcoplasmic contractile protein gene mutation;
Treatment with any investigational drug or device within the 30 days;
Unable to comply with the protocol as determined by the Investigator;
Positive for hepatitis B, hepatitis C or HIV

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00864851

Locations

Australia, Victoria
The Royal Melbourne Hospital	Active, not recruiting
Parkville, Victoria, Australia, 3052
Czech Republic
1st School of Medicine, Charles University	Recruiting
Prague, Czech Republic
Contact: Lubor Golan 420 224962366
Principal Investigator: Lubor Golan
Poland
Instytut Kardiologii	Recruiting
Warsaw, Poland
Contact: Lidia Chojnowska 48 22 343 42 72
Principal Investigator: Lidia Chojinowska

Sponsors and Collaborators

Shire Human Genetic Therapies, Inc.

Investigators

Study Director:

Pedro Huertas, M.D., Ph.D.

Shire Human Genetic Therapies, Inc.

More Information

No publications provided

Responsible Party:	Senior Medical Director ( Pedro Huertas, M.D., Ph.D )
Study ID Numbers:	TKT028
Study First Received:	March 18, 2009
Last Updated:	October 20, 2009
ClinicalTrials.gov Identifier:	NCT00864851 History of Changes
Health Authority:	Poland: Ministry of Health

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 09, 2010