Replagal Enzyme Replacement Therapy for Children With Fabry Disease
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: Agalsidase alfa
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 7 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Lysosomes; Storage; Glycolipid; Fabry disease; Stroke; Children; Pediatrics

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)
    

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.