Safety Study of Replagal® Therapy in Children With Fabry Disease

• ClinicalTrials.gov Identifier: NCT01363492
• Recruitment Status: Completed
• First Posted: June 1, 2011
• Results First Posted: May 20, 2014
• Last Update Posted: June 9, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: Replagal (agalsidase alfa)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Clinical Trial of Replagal® Enzyme Replacement Therapy in Children With Fabry Disease Who Are Naive to Enzyme Replacement Therapy
• Actual Study Start Date: May 12, 2011
• Actual Primary Completion Date: April 17, 2013
• Actual Study Completion Date: April 17, 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Replagal 0.2 mg/kg every other week (EOW)	Biological: Replagal (agalsidase alfa); 0.2 mg/kg administered over 40 minutes every other week (EOW); Other Name: agalsidase alfa

Outcome Measures

Primary Outcome Measures :

1. Number of Serious Adverse Event (SAE) [ Time Frame: Baseline to week 55 ]
2. Number of Treatment Emergent Adverse Event (TEAE) [ Time Frame: Baseline to week 55 ]
3. Development of IgG Anti-Agalsidase Alfa Antibody [ Time Frame: Baseline to Week 55 ]
   Reflects development of Anti-Agalsidase antibodies post baseline
4. Change From Baseline in Heart Rate Variability Parameter SDNN [ Time Frame: Baseline to week 55 ]
5. Change From Baseline in Heart Rate Variability Parameter rMSSD [ Time Frame: Baseline to week 55 ]
6. Change From Baseline in Heart Rate Variability Parameter pNN50 [ Time Frame: Baseline to week 55 ]

Secondary Outcome Measures :

1. Change From Baseline in LVMI [ Time Frame: Baseline to week 55 ]
2. Change From Baseline in MFS [ Time Frame: Baseline to week 55 ]
3. Change From Baseline in Plasma Gb3 [ Time Frame: Baseline to week 55 ]
4. Change From Baseline in Urine Gb3 [ Time Frame: Baseline to week 55 ]

Eligibility Criteria

• Ages Eligible for Study: 7 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Georgia

Emory Division of Medical Genetics

Decatur, Georgia, United States, 30033

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Texas

Baylor University Medical Center

Dallas, Texas, United States, 75246

United States, Utah

University of Utah Hospital

Salt Lake City, Utah, United States, 84132

United States, Virginia

O & O Alpan LLC

Fairfax, Virginia, United States, 22152

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goker-Alpan O, Longo N, McDonald M, Shankar SP, Schiffmann R, Chang P, Shen Y, Pano A. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naive to enzyme replacement therapy. Drug Des Devel Ther. 2016 May 25;10:1771-81. doi: 10.2147/DDDT.S102761. eCollection 2016.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01363492
• Other Study ID Numbers: HGT-REP-084
• First Posted: June 1, 2011
• Results First Posted: May 20, 2014
• Last Update Posted: June 9, 2021
• Last Verified: May 2021

Keywords provided by Takeda ( Shire ):

agalsidase alfa; Replagal; Enzyme Replacement Therapy

Additional relevant MeSH terms:

Fabry Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders