Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.

Study Overview
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Brief Summary
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This is a prospective, observational multicenter study to collect blood from patients with mucopolysaccharidosis type IH undergoing laronidase therapy and a stem cell transplant. Sixteen patients will be enrolled over a 24 month period.

Official Title
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Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.

Conditions
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Hematopoietic Cell Transplantation, Mucopolysaccharidosis Type I

Intervention / Treatment
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* Drug: Laronidase therapy and a stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 0 to 3 years of age Meet protocol specific eligibility criteria for allogeneic HCT for MPS IH Planning to receive laronidase both pre and post-transplant in an inpatient setting as part of standard-of-care treatment. Virtually all patients with MPSIH being considered for transplantation at the University of Minnesota are already receiving enzyme infusions, and it is standard practice to continue to give enzyme infusions to 8 weeks post-transplant. Therefore, participation will not modify the treatment course. Exclusion Criteria: Patient's parent/ legal guardians are unable to provide informed consent.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Collect blood from patients with MPS-IH) undergoing laronidase therapy and stem cell transplant.<br>The primary aim is to characterize the PK of IV laronidase in individuals with MPS IH and identify patient specific covariates that impact drug exposure. The secondary aim is to identify key differences pre-and post-HCT leading to variability in PK parameters for patients receiving IV laronidase therapy for the treatment of MPS-IH. | Drug: Laronidase therapy and a stem cell transplant<br>* To identify key differences leading to variability in PK parameters for patients receiving IV laronidase therapy for the treatment of MPS-IH. There will be 12 samples per patient (6 pre-transplant and 6-post-transplant). Laronidase will be administered IV per protocol using standard dosing (0.58 mg/kg intravenously on a weekly basis), and six (n=6) blood samples will be collected over 24 hours for the determination of mononuclear cell lysates and plasma laronidase concentrations for a total of 18mL. The second PK monitoring will be obtained using the same PK design but following complete or near-completedonor derived myeloid engraftment which is evaluated at different time pointspost-HCT (day 30, day 42, day 60). The standard is to continue ERT through 8 weeks post-transplant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify covariates that impact drug exposure | Measure indicators for body size and maturation contribute to variability in laronidase exposure in patients with MPS IH. | 2 years | 
| Identify key differences pre- and post-HCT leading to variability in PK parameters | Measure endogenous source of enzyme present in relation to the transplanted cells. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS I, HCT