Safety Study of Replagal® Therapy in Children With Fabry Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01363492
First received: March 31, 2011
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Fabry Disease
Biological: Replagal (agalsidase alfa)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Serious Adverse Event (SAE) [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: Yes ]
  • Number of Treatment Emergent Adverse Event (TEAE) [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: Yes ]
  • Development of IgG Anti-Agalsidase Alfa Antibody [ Time Frame: Baseline to Week 55 ] [ Designated as safety issue: Yes ]
    Reflects development of Anti-Agalsidase antibodies post baseline

  • Change From Baseline in Heart Rate Variability Parameter SDNN [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]
  • Change From Baseline in Heart Rate Variability Parameter rMSSD [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]
  • Change From Baseline in Heart Rate Variability Parameter pNN50 [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in LVMI [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]
  • Change From Baseline in MFS [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]
  • Change From Baseline in Plasma Gb3 [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]
  • Change From Baseline in Urine Gb3 [ Time Frame: Baseline to week 55 ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: May 2011
Study Completion Date: June 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01363492

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
Principal Investigator: Ozlem Goker-Alpan, MD O & O Alpan LLC
Principal Investigator: Nicola Longo, MD, PhD University of Utah Hospital
Principal Investigator: Raphael Schiffmann, MD Baylor Health Care System
Principal Investigator: Suma P. Shankar, MD, PhD Emory Division of Medical Genetics
Principal Investigator: Marie T. McDonald, MD Duke University
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01363492     History of Changes
Other Study ID Numbers: HGT-REP-084
Study First Received: March 31, 2011
Results First Received: March 25, 2014
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by 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

ClinicalTrials.gov processed this record on October 01, 2014