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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT00864851
First received: March 18, 2009
Last updated: December 13, 2012
Last verified: December 2012
History of Changes
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:

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 ]

Enrollment: 40
Study Start Date: December 2008
Study Completion Date: July 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Replagal every two weeks Biological: Replagal
Comparison of different dosing regimens
Other Name: algasidase alfa
Biological: Replagal
Replagal IV , comparison of doses
Other Name: algasidase alfa
Active Comparator: Replagal every week Biological: Replagal
Comparison of different dosing regimens
Other Name: algasidase alfa
Biological: Replagal
Replagal IV , comparison of doses
Other Name: algasidase alfa
Active Comparator: Replagal every week Biological: Replagal
Comparison of different dosing regimens
Other Name: algasidase alfa
Biological: Replagal
Replagal IV , comparison of doses
Other Name: algasidase alfa

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
United States, Arizona
AKDHC Tucson Access Center
Tucson, Arizona, United States, 85719
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, New York
New York Unversity School of Medicine
New York, New York, United States, 10016
United States, Virginia
O & O Alpan, LLC
Springfield, Virginia, United States, 22152
Australia, Victoria
The Royal Melbourne Hospital
Parkville, Victoria, Australia, 3052
Czech Republic
The Charles University Hospital
Prague, Czech Republic, 128 OO
Finland
Turku University Central Hospital
Turku, Finland, FI-20520
Paraguay
Gobemador Irala y Coronel Lopez - Barrio Sojania
Asuncion, Paraguay
Poland
Szpital Uniwersytecki w Krakowie
Krakow, Poland, 31-066
Instytut Kardiologii
Warsaw, Poland, 04-628
Slovenia
General Hospital Slovenj Gradec
Slovenj Gradec, Slovenia, SI 2380
United Kingdom
Salford Royal NHS Foundation Trust
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Shire Human Genetic Therapies, Inc.
Investigators
Principal Investigator: Gregory M. Pastores, MD New York University School of Medicine
Principal Investigator: Ademola K. Abiose, MD University of Iowa
Principal Investigator: Bojan Vujkovac, MD General Hospital Slovenj Gradec
Principal Investigator: Myrl D. Holida, PA-C University of Iowa
Principal Investigator: Kathleen Nicholls, MB.BS, MD Melbourne Health
Principal Investigator: Jacek Musial, MD, PhD Szpital Uniwersytecki w Krakowie
Principal Investigator: Lubor Golan, MD The Charles University Hospital
Principal Investigator: Derlis Emilio Gonzalez Rodriguez, MD Gobernador Irala Y Coronel Lopez - Barrio Sajonia
Principal Investigator: Lidia Chojnowska, MD, PhD Instytut Kardiologii
Principal Investigator: Stephen Waldek, MB BCh, FRCP Salford Royal NHS Foundation Trust
Principal Investigator: Ilkka Kantola, MD, PhD University of Turku
Principal Investigator: Y. Howard Lien, MD, PhD AKDHC Tucson Access Center
Principal Investigator: Ozlem Goker-Alpan, MD O & O Alpan LLC
Principal Investigator: Reena Sharma, MD Salford Royal NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier: NCT00864851     History of Changes
Other Study ID Numbers: TKT028
Study First Received: March 18, 2009
Last Updated: December 13, 2012
Health Authority: Poland: Ministry of Health
Czech Republic: State Institute for Drug Control
Australia: Department of Health and Ageing Therapeutic Goods Administration
Paraguay: Ministerio de Salud Pública y Bienestar Social
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Finland: Finnish Medicines Agency
United States: Food and Drug Administration
Slovenia: Agency for Medicinal Products - Ministry of Health

Additional relevant MeSH terms:
Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 16, 2013