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

NCT ID: NCT00864851

Last Updated: 2021-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-29
• Study Completion Date: 2012-07-05

Brief Summary

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.

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 midwall 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 is to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on the reduction of left ventricular mass as measured by echocardiography.

The secondary objectives of this study are to compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV weekly) on each of the following: exercise tolerance; improvement in disease-specific quality of life in heart failure patients; improvement of heart failure symptoms; magnitude of reduction in Gb3; rate of decline in renal function and improvement in the severity of proteinuria/albuminuria; and safety.

An alternative treatment regimen of 0.4 mg/kg Replagal IV weekly will also be explored but without formal comparison to the 0.2 mg/kg regimens. The investigation of the safety and efficacy of the 0.4 mg/kg IV weekly regimen is a secondary objective of this study.

Conditions

Fabry Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Replagal 0.2 mg/kg, IV, every other week

Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.

Group Type: ACTIVE_COMPARATOR

Replagal

Intervention Type: BIOLOGICAL

Intravenous (IV) infusion for 12 months

Replagal 0.2 mg/kg, IV, weekly

Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.

Group Type: ACTIVE_COMPARATOR

Replagal

Intervention Type: BIOLOGICAL

Intravenous (IV) infusion for 12 months

Replagal 0.4 mg/kg, IV, weekly

Patients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.

Group Type: ACTIVE_COMPARATOR

Replagal

Intervention Type: BIOLOGICAL

Intravenous (IV) infusion for 12 months

Interventions

Replagal

Intravenous (IV) infusion for 12 months

Intervention Type: BIOLOGICAL

Other Intervention Names

algasidase alfa

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

AKDHC Tucson Access Center

Tucson, Arizona, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

New York Unversity School of Medicine

New York, New York, United States

O & O Alpan, LLC

Springfield, Virginia, United States

The Royal Melbourne Hospital

Parkville, Victoria, Australia

The Charles University Hospital

Prague, , Czechia

Turku University Central Hospital

Turku, , Finland

Gobemador Irala y Coronel Lopez - Barrio Sojania

Asunción, , Paraguay

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

Instytut Kardiologii

Warsaw, , Poland

General Hospital Slovenj Gradec

Slovenj Gradec, , Slovenia

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Countries

United States; Australia; Czechia; Finland; Paraguay; Poland; Slovenia; United Kingdom

References

Malek LA, Chojnowska L, Spiewak M, Klopotowski M, Misko J, Petryka J, Milosz B, Ruzyllo W. Cardiac magnetic resonance imaging in patients with Fabry's disease. Kardiol Pol. 2010 Aug;68(8):929-34.

Reference Type: RESULT

PMID: 20730727 (View on PubMed)

Other Identifiers

2007-005543-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TKT028

Identifier Type: -

Identifier Source: org_study_id