Replagal Enzyme Replacement Therapy for Children With Fabry Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00084084
First received: June 5, 2004
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

Primary Objective(s):

  • To assess the safety of Replagal at a dose of 0.2 mg/kg administered over 40 (+/-10) minutes in children with Fabry disease
  • To assess the effect of Replagal on heart rate variability in patients 7 to 17 years of age

Secondary Objective(s):

  • To determine the pharmacokinetics of Replagal at baseline and after the initiation of enzyme replacement therapy (ERT)
  • To determine exploratory measurements of efficacy including renal function (ie, estimated glomerular filtration rate [eGFR] and creatinine clearance), clinical outcomes (in Cohorts 1 and 2), and sweating and left ventricular mass index (LVMI) (Cohort 1, Phase 1 only)

Condition Intervention Phase
Fabry Disease
Drug: Agalsidase alfa
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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 Have Completed Study TKT023 or Who Are Naive to Enzyme Replacement Therapy

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Patients Who Experienced At Least One Adverse Event (AE) [ Time Frame: 362 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) [ Time Frame: 341 weeks ] [ Designated as safety issue: No ]
    AUC0-∞ is a measure of the total exposure to a drug.

  • Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) [ Time Frame: 341 weeks ] [ Designated as safety issue: No ]
    Cmax is the peak plasma concentration of a drug after administration.


Other Outcome Measures:
  • Heart Rate Variability - Change From Baseline at Week 185 in SDNN [ Time Frame: Week 185 ] [ Designated as safety issue: No ]
    Heart rate variability was assessed by 2-hour Holter monitoring. Standard deviation of all filtered RR intervals over the length of the analysis (SDNN) was measured.


Enrollment: 17
Study Start Date: June 2004
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Agalsidase alfa (Cohort 1)
Cohort 1: Patients who completed TKT023.
Drug: Agalsidase alfa
0.2 mg/kg agalsidase alfa administered by IV infusion over 40 (+/- 10) minutes every other week for 52 weeks, with periodic reassessments for study continuation beyond 52 weeks
Other Name: Replagal
Experimental: Agalsidase Alfa (Cohort 2)
Cohort 2: Treatment-naive patients.
Drug: Agalsidase alfa
0.2 mg/kg agalsidase alfa administered by IV infusion over 40 (+/- 10) minutes every other week for 52 weeks, with periodic reassessments for study continuation beyond 52 weeks
Other Name: Replagal

Detailed Description:

TKT029 is an open label multi-center study to assess the safety of enzyme replacement therapy with Replagal (agalsidase alfa) in children with Fabry disease, who have completed 6 months of agalsidase alfa therapy in study TKT023 (Cohort 1) or who are treatment-naïve (Cohort 2) and meet all inclusion/exclusion criteria of this study. The study will consist of every other week treatment with Replagal for 52 weeks, with periodic reassessments by Shire HGT for continuation of the study beyond 52 weeks. A decision on the part of the study sponsor to terminate the study may be made at any time.

In Cohort 1, safety and clinical measurement assessments performed during Week 25 or 26 of Study TKT023 served as the baseline assessments for TKT029. Patients in Cohort 1 began treatment with Replagal manufactured using a roller bottle process (Replagal RB); this portion of treatment is denoted as Cohort 1, Phase 1. Safety evaluation visits for Cohort 1, Phase 1 were to be performed at Weeks 13, 25, 55, and every 26 weeks thereafter until the patient discontinued from the study or transitioned to treatment with Replagal manufactured using a bioreactor process (Replagal AF). The transition to Replagal AF marked the restart of the study clock and was denoted as Cohort 1, Phase 2. Safety evaluation visits for Cohort 1, Phase 2 will be performed at Weeks 1, 13, 25, 55, and every 26 weeks thereafter until the patient discontinues from or the sponsor terminates the study.

Patients in Cohort 2 will receive treatment with Replagal AF only; therefore there is only 1 study phase for these patients. Screening assessments performed at Week -1 will serve as the baseline assessments for this study. Safety evaluation visits for Cohort 2 will be performed at Weeks 13, 25, 37, 55 and every 26 weeks thereafter until the patients discontinues from or the sponsor terminates the study.

The final study visit for both cohorts will follow 30 days after the study study drug infusion, at which time a final safety evaluation will be performed. Patients who complete the study will be interviewed by telephone 30 days after their last study infusion for resolution of any outstanding adverse events (AEs) or concomitant medication changes. Any patient who withdraws early from the study will have a final study visit 30 days after the last study drug infusion, at which time a final safety evaluation will be performed.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1a. For Cohort 1 (both phases):

- Patients must have completed all study requirements and assessments for Study TKT023 less than 30 (+/-7) days prior to enrolling in Study TKT029 and must have no safety or medical issues that contraindicate participation.

OR

1b. For Cohort 2:

  • The patient is between 7 and 17 years of age at the time of informed consent, inclusive.
  • The patient must be ERT-naive.
  • The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alpha-galactosidase A activity measured in serum, leukocytes, or fibroblasts. Male patients who do not already have a documented deficiency of alpha-galactosidase A activity will provide a blood sample during screening for determination of alpha-galactosidase A activity level in their serum.

OR

- The patient is a heterozygous female or hemizygous male with Fabry disease as confirmed by a mutation of the alpha-galactosidase A gene. Patients who do not already have a documented mutation of the alpha-galactosidase A gene will provide a blood sample during screening for genotyping.

2. 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.

3. The minor child must assent to participate in the protocol and the parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed concent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legal guardian(s).

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for this study:

  • Patient and/or the patient's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study.
  • Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor.
  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: NCT00084084

Locations
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
Tucson Access Center of Arizona Kidney Disease Hypertension Center
Tucson, Arizona, United States, 85719
United States, Florida
Children's Physician Group
Palm Beach Gardens, Florida, United States, 33410
United States, Louisiana
Christus St. Patrick Hospital
Lake Charles, Louisiana, United States, 70601
United States, Maryland
Clinical Center, National Institutes of Health
Bethesda, Maryland, United States, 20892
Memorial Hospital
Easton, Maryland, United States, 21601
United States, Missouri
St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
United States, New York
NYU School of Medicine
New York, New York, United States, 10016
United States, Pennsylvania
Sacred Heart Hospital
Allentown, Pennsylvania, United States, 18102
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
University of Tennessee, Health Science Center
Memphis, Tennessee, United States, 38163
United States, Texas
Institute of Metabolic Diseases
Dallas, Texas, United States, 75226
United States, Virginia
Office of Michael Cohen
Stafford, Virginia, United States, 22556
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Raphael Schiffman, MD Institute of Metabolic Disease, Baylor Research Institute
Principal Investigator: Ray Pais, MD, FAAP East Tennessee Children's Hospital
Principal Investigator: Y. Howard Lien, MD, PhD Tuscon Access Center of Arizona Kidney Disease Hypertension Center
Principal Investigator: Gregory M. Pastores, MD New York University School of Medicine
Principal Investigator: Manju Thomas, MD Sacred Heart Hospital
Principal Investigator: Alison Whelan, MD St. Louis Children's Hospital
Principal Investigator: Michael E. Cohen, MD Office of Michael Cohen
Principal Investigator: Lynda Bideau, MD Children's Physicians Group
Principal Investigator: Yang-Tze Yoko Broussard, MD Christus St. Patrick Hospital
Principal Investigator: Victoria Castaneda, MD East Tennessee Children's Hospital
Principal Investigator: Li-Wen Lai, PhD University of Arizona Health Sciences Center
Principal Investigator: Tanya J. Lehky, MD Clinical Center, National Institutes of Health
Principal Investigator: Tyler Reimschisel, MD St. Louis Children's Hospital
Principal Investigator: Brian J. Corden, MD, PhD Memorial Hospital
Principal Investigator: Karen L. Johnson, MD, MPH University of Tennessee Health Science Center
Principal Investigator: Joe T. Clarke, MD, PhD The Hospital for Sick Children
Principal Investigator: Leslie F. Carroll, MD Sacred Heart Hospital
Principal Investigator: Rick A. Martin, MD St. Louis Children's Hospital
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00084084     History of Changes
Other Study ID Numbers: TKT029
Study First Received: June 5, 2004
Results First Received: August 1, 2013
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Shire:
Lysosomes
Storage
Glycolipid
Fabry disease
Stroke
Children
Pediatrics

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 September 18, 2014