Safety Study of Replagal® Therapy in Children With Fabry Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of Replagal in children with Fabry disease who who have not previously been treated with enzyme replacement therapy (ERT).

Detailed Description
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In 2008, a change in the agalsidase alfa drug substance manufacturing process was made. There are no changes to the drug product formulation, manufacturing site, manufacturing process, or container closure. An agalsidase alfa bioreactor manufacturing process (agalAF1) utilizing animal component-free media replaced the previous roller bottle (RB) process. This study will evaluate the safety of Replagal AF, manufactured using the new bioreactor process at a dose of 0.2 mg/kg infused IV over 40 minutes, every other week (EOW) in children with Fabry disease who are 7 years to less than 18 years of age and who are naive to ERT.

Official Title
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An Open-Label Clinical Trial of Replagal® Enzyme Replacement Therapy in Children With Fabry Disease Who Are Naive to Enzyme Replacement Therapy

Conditions
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Fabry Disease

Intervention / Treatment
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* Biological: Replagal (agalsidase alfa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all of the following criteria to be enrolled in this study. All patients must be diagnosed with Fabry disease by the following criteria: Male Patients: The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alfa-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the alfa-galactosidase-A gene. Female Patients: The patient is a heterozygous female with Fabry disease as confirmed by a mutation of the alfa-galactosidase A gene. Note: If the diagnosis of Fabry disease is previously documented in the patient's medical record, screening tests do not need to be repeated. The patient is 7 to <18 years of age The patient is ERT-naïve Adequate general health (as determined by the Investigators) to undergo the specified phlebotomy regimen and protocol-related procedures and no safety or medical contraindications for participation The minor child must assent to participate in the protocol and the parent(s) or legally authorized representative(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legally authorized representative(s) Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study. Patient and/or the patient's parent(s) or legally authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study Patient is unable to comply with the protocol, eg, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor. Otherwise unsuitable for the study, in the opinion of the Investigator.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Replagal 0.2 mg/kg every other week (EOW)<br> | Biological: Replagal (agalsidase alfa)<br>* 0.2 mg/kg administered over 40 minutes every other week (EOW)<br>* Other names: agalsidase alfa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Serious Adverse Event (SAE) |  | Baseline to week 55 | 
| Number of Treatment Emergent Adverse Event (TEAE) |  | Baseline to week 55 | 
| Development of IgG Anti-Agalsidase Alfa Antibody | Reflects development of Anti-Agalsidase antibodies post baseline | Baseline to Week 55 | 
| Change From Baseline in Heart Rate Variability Parameter SDNN |  | Baseline to week 55 | 
| Change From Baseline in Heart Rate Variability Parameter rMSSD |  | Baseline to week 55 | 
| Change From Baseline in Heart Rate Variability Parameter pNN50 |  | Baseline to week 55 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in LVMI |  | Baseline to week 55 | 
| Change From Baseline in MFS |  | Baseline to week 55 | 
| Change From Baseline in Plasma Gb3 |  | Baseline to week 55 | 
| Change From Baseline in Urine Gb3 |  | Baseline to week 55 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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agalsidase alfa, Replagal, Enzyme Replacement Therapy