Replagal Enzyme Replacement Therapy for Children With Fabry Disease

NCT ID: NCT00084084

Last Updated: 2021-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-10
• Study Completion Date: 2011-06-15

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.

Conditions

Fabry Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Agalsidase alfa (Cohort 1)

Cohort 1: Patients who completed TKT023.

Group Type: EXPERIMENTAL

Agalsidase alfa

Intervention Type: DRUG

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

Agalsidase Alfa (Cohort 2)

Cohort 2: Treatment-naive patients.

Group Type: EXPERIMENTAL

Agalsidase alfa

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Replagal

Eligibility 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.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Tucson Access Center of Arizona Kidney Disease Hypertension Center

Tucson, Arizona, United States

University of Arizona Health Sciences Center

Tucson, Arizona, United States

Children's Physician Group

Palm Beach Gardens, Florida, United States

Christus St. Patrick Hospital

Lake Charles, Louisiana, United States

Clinical Center, National Institutes of Health

Bethesda, Maryland, United States

Memorial Hospital

Easton, Maryland, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

NYU School of Medicine

New York, New York, United States

Sacred Heart Hospital

Allentown, Pennsylvania, United States

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

University of Tennessee, Health Science Center

Memphis, Tennessee, United States

Institute of Metabolic Diseases

Dallas, Texas, United States

Office of Michael Cohen

Stafford, Virginia, United States

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 25425121 (View on PubMed)

Other Identifiers

TKT029

Identifier Type: -

Identifier Source: org_study_id