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

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.

Study Overview

• Status: Recruiting
• Conditions: Mucopolysaccharidosis Type I; Hematopoietic Cell Transplantation
• Intervention / Treatment: Drug: Laronidase therapy and a stem cell transplant

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Kim Nelson, RN; Phone Number: 612-273-2925; Email: knelso62@fiarview.org

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Masonic Cancer Center
      • Contact: Kim Nelson, RN; Phone Number: 612-273-2925

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 3 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Study entry is open to pediatric patients regardless of gender or ethnic background. While there will be every effort to seek out and include females and minority patients, the patient population is dependent upon the MPS-IH populations at the University of Minnesota.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Collect blood from patients with MPS-IH) undergoing laronidase therapy and stem cell transplant.; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Paul Orchard, University of Minnesota Masonic Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: November 22, 2022
• First Posted (Actual): December 2, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: MPS I; HCT
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis I
• Other Study ID Numbers: 2021LS144; NCI-2022-09774 (Registry Identifier: NCI Trial ID); MT2021-29 (Other Identifier: University of Minnesota Masonic Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No