Safety Study of Replagal® Therapy in Children With Fabry Disease

Phase 2

Completed

• Conditions: Fabry Disease
• Interventions: Biological: Replagal (agalsidase alfa)

• Registration Number: NCT01363492
• Lead Sponsor: Shire

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2011-03-31
• Study Start: 2011-05-12
• Study First Submitted QC: 2011-05-27
• Study First Posted: 2011-06-01
• Primary Completion: 2013-04-17
• Study Completion: 2013-04-17
• Results First Submitted: 2014-03-25
• Results First Submitted QC: 2014-04-17
• Results First Posted: 2014-05-20
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-24
• Last Update Posted: 2021-06-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Patients must meet all of the following criteria to be enrolled in this study.

1. 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.

2. The patient is 7 to <18 years of age

3. The patient is ERT-naïve

4. 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

5. 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.

1. 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
2. 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.
3. Otherwise unsuitable for the study, in the opinion of the Investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Replagal 0.2 mg/kg every other week (EOW)	Replagal (agalsidase alfa)	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
Change From Baseline in LVMI	Baseline to week 55

Trial Locations

Locations (5)

Emory Division of Medical Genetics; 🇺🇸 Decatur, Georgia, United States

University of Utah Hospital; 🇺🇸 Salt Lake City, Utah, United States

O & O Alpan LLC; 🇺🇸 Fairfax, Virginia, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States