Replagal Enzyme Replacement Therapy for Children With Fabry Disease
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
1 other identifier
interventional
17
2 countries
14
Brief Summary
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jun 2004
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 5, 2004
CompletedFirst Posted
Study publicly available on registry
June 7, 2004
CompletedStudy Start
First participant enrolled
June 10, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 15, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
June 15, 2011
CompletedResults Posted
Study results publicly available
October 10, 2013
CompletedJuly 30, 2021
July 1, 2021
7 years
June 5, 2004
August 1, 2013
July 2, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Patients Who Experienced At Least One Adverse Event (AE)
362 weeks
Secondary Outcomes (8)
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81
Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.
- +3 more secondary outcomes
Other Outcomes (1)
Heart Rate Variability - Change From Baseline at Week 185 in SDNN
Week 185
Study Arms (2)
Agalsidase alfa (Cohort 1)
EXPERIMENTALCohort 1: Patients who completed TKT023.
Agalsidase Alfa (Cohort 2)
EXPERIMENTALCohort 2: Treatment-naive patients.
Interventions
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
Eligibility Criteria
You may qualify if:
- a. 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.
- b. 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.
- \- 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.
- \. 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.
- \. 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).
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Shirelead
Study Sites (14)
Tucson Access Center of Arizona Kidney Disease Hypertension Center
Tucson, Arizona, 85719, United States
University of Arizona Health Sciences Center
Tucson, Arizona, 85724, United States
Children's Physician Group
Palm Beach Gardens, Florida, 33410, United States
Christus St. Patrick Hospital
Lake Charles, Louisiana, 70601, United States
Clinical Center, National Institutes of Health
Bethesda, Maryland, 20892, United States
Memorial Hospital
Easton, Maryland, 21601, United States
St. Louis Children's Hospital
St Louis, Missouri, 63110, United States
NYU School of Medicine
New York, New York, 10016, United States
Sacred Heart Hospital
Allentown, Pennsylvania, 18102, United States
East Tennessee Children's Hospital
Knoxville, Tennessee, 37916, United States
University of Tennessee, Health Science Center
Memphis, Tennessee, 38163, United States
Institute of Metabolic Diseases
Dallas, Texas, 75226, United States
Office of Michael Cohen
Stafford, Virginia, 22556, United States
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (1)
Schiffmann R, Pastores GM, Lien YH, Castaneda V, Chang P, Martin R, Wijatyk A. Agalsidase alfa in pediatric patients with Fabry disease: a 6.5-year open-label follow-up study. Orphanet J Rare Dis. 2014 Nov 26;9:169. doi: 10.1186/s13023-014-0169-6.
PMID: 25425121DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Shire
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 5, 2004
First Posted
June 7, 2004
Study Start
June 10, 2004
Primary Completion
June 15, 2011
Study Completion
June 15, 2011
Last Updated
July 30, 2021
Results First Posted
October 10, 2013
Record last verified: 2021-07