Fabry Disease MedDRA version: 14.1 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Replagal
Product Name: Replagal
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: agalsidase alpha
Other descriptive name: Replagal
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Shire Human Genetic Therapies, Inc. (Shire HGT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient is = 18 years-old. 2a. The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of a-galactosidase-A activity measured in serum, leukocytes, or fibroblasts. Male patients who do not already have a documented deficiency of a-galactosidase-A activity will provide a blood sample during Screening for determination of a-galactosidase-A activity level in their serum. OR 2b. The patient is a heterozygous female with Fabry disease as confirmed by a mutation of the a-agalactosidase A gene. Female patients who do not already have a documented mutation of the a-galactosidase A gene will provide a blood sample during Screening for genotyping. 3. The patient has not received enzyme replacement therapy (ERT) for Fabry disease (i.e., the patient is ERT-naïve). 4. The patient’s LVM/h is > 50 g/m2.7 for male patients and > 47 g/m2.7 for female patients, as measured by echocardiography, which is the upper limit of normal. 5. Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have a negative pregnancy test at the time of enrollment and as required throughout their participation in the study. 6. The patient has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 39 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. The patient has documented NYHA functional class IV heart failure symptoms. 2. The patient has clinically significant systemic hypertension defined as an untreated resting blood pressure (BP) > 160 / 110 mmHg or poorly controlled hypertension defined as a BP > 150 / 100, while receiving medication(s) for treatment of hypertension. 3. The patient has hemodynamically significant valvular stenosis or regurgitation by Doppler echocardiography. 4. The patient is morbidly obese, defined as having a body mass index > 39 kg/m2. 5. The patient has a known autosomal dominant sarcoplasmic contractile protein gene mutation. 6. The patient has received treatment with any investigational drug or device within the 30 days prior to study entry. 7. The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator. 8. The patient has a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg administered intravenously (IV) every other week and 0.2 mg/kg IV every week) on the reduction from baseline in left ventricular mass (LVM) as measured by echocardiography;Secondary Objective: To compare the effects of 2 dosing regimens of Replagal (0.2 mg/kg IV every other week and 0.2 mg/kg IV every week) - on exercise tolerance by maximal oxygen consumption (Vo2max) using the standard exponential exercise protocol (STEEP) and by the 6-Minute Walk Test (6MWT) - on the improvement from baseline in disease-specific quality of life (QoL) using the summary score of the Minnesota Living with Heart Failure questionnaire (MLHF-Q) - on the improvement from baseline in New York Heart Association (NYHA) functional class for heart failure symptoms - as assessed by adverse events (AEs), concomitant medications, vital signs, physical examinations, electrocardiograms (ECGs), anti-agalsidase alfa antibodies and standard clinical and laboratory (hematology, serum chemistry, and urinalysis) measurements;Primary end point(s): The primary endpoint of this study will be the change from Baseline to Week 53 in LVM normalized to height (LVM/h), as measured by echocardiography.;Timepoint(s) of evaluation of this end point: week 53 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Change from Baseline to Week 53 in exercise tolerance, as measured by Vo2max at peak exercise using the STEEP exercise protocol and by distance walked in meters (m) using the 6MWT 2. Change from Baseline to Week 53 in NYHA Class 3.Change from Baseline to Week 53 in QoL using the MLHF-Q summary score 4. Safety: AEs, concomitant medications, vital signs, physical examinations, ECGs, anti-agalsidase alfa antibodies and standard clinical assessments;Timepoint(s) of evaluation of this end point: week 53 | — |
Countries
Australia, Czech Republic, Finland, Paraguay, Slovenia, United Kingdom, United States
Contacts
Public ContactClinical Project Manager
Shire Human Genetic Therapies, Inc.
Outcome results
None listed