Safety Study of Replagal® Therapy in Children With Fabry Disease

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

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).

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: Replagal (agalsidase alfa)

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory Division of Medical Genetics
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22152
      • O & O Alpan LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: agalsidase alfa

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 12, 2011
• Primary Completion (ACTUAL): April 17, 2013
• Study Completion (ACTUAL): April 17, 2013

Study Registration Dates

• First Submitted: March 31, 2011
• First Submitted That Met QC Criteria: May 27, 2011
• First Posted (ESTIMATE): June 1, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Enzyme Replacement Therapy; Replagal; agalsidase alfa
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: HGT-REP-084