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Replagal Enzyme Replacement Therapy for Children With Fabry Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00084084
Recruitment Status : Completed
First Posted : June 7, 2004
Results First Posted : October 10, 2013
Last Update Posted : April 16, 2014
Sponsor:
Information provided by (Responsible Party):
Shire

Tracking Information
First Submitted Date  ICMJE June 5, 2004
First Posted Date  ICMJE June 7, 2004
Results First Submitted Date  ICMJE August 1, 2013
Results First Posted Date  ICMJE October 10, 2013
Last Update Posted Date April 16, 2014
Study Start Date  ICMJE June 2004
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2013)
Patients Who Experienced At Least One Adverse Event (AE) [ Time Frame: 362 weeks ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2013)
  • Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) [ Time Frame: 341 weeks ]
    AUC0-∞ is a measure of the total exposure to a drug.
  • Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) [ Time Frame: 341 weeks ]
    Cmax is the peak plasma concentration of a drug after administration.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: August 1, 2013)
Heart Rate Variability - Change From Baseline at Week 185 in SDNN [ Time Frame: Week 185 ]
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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Replagal Enzyme Replacement Therapy for Children With Fabry Disease
Official Title  ICMJE 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
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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fabry Disease
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Agalsidase alfa (Cohort 1)
    Cohort 1: Patients who completed TKT023.
    Intervention: Drug: Agalsidase alfa
  • Experimental: Agalsidase Alfa (Cohort 2)
    Cohort 2: Treatment-naive patients.
    Intervention: Drug: Agalsidase alfa
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 7, 2012)
17
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
19
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00084084
Other Study ID Numbers  ICMJE TKT029
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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 NYU Langone Health
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
PRS Account Shire
Verification Date March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP