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

Shire

Status and phase: Completed; Phase 3

Conditions: Fabry Disease

Treatments: Biological: Replagal

Study type: Interventional

Funder types: Industry

Identifiers

NCT00864851

TKT028

2007-005543-22 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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44 participants in 3 patient groups

Replagal 0.2 mg/kg, IV, every other week

Active Comparator group

Description:

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

Treatment:

Biological: Replagal

Replagal 0.2 mg/kg, IV, weekly

Active Comparator group

Description:

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

Treatment:

Biological: Replagal

Replagal 0.4 mg/kg, IV, weekly

Active Comparator group

Description:

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

Treatment:

Biological: Replagal