Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

Pilot Study of Administration of Intravenous Laronidase Following Allogeneic Transplantation for Hurler Syndrome

This is a single center pilot study in which Laronidase will be given weekly for two years in patients with Hurler syndrome, also known as mucopolysaccharide IH (MPS I, Hurler syndrome), that have previously been treated with an allogeneic transplant.

Study Overview

• Status: Completed
• Conditions: Hurler Syndrome
• Intervention / Treatment: Drug: Laronidase

Detailed Description

This 2-year open-label pilot study of laronidase includes patients (age 5-13 years) who are at least 2 years post-hematopoietic cell transplantation (HCT) and donor engrafted. Outcomes are assessed semi-annually and compared to historic controls. Eligible patients will receive Laronidase as an infusion over several hours once a week at a local site. The dosing of enzyme will be the standard doses recommended by Genzyme.

The findings of this Pilot Study will be used to assess whether a subsequent larger study can be conducted.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant >2 years previously
• Age <14 years old
• >10% engrafted based on recent testing (<4 months prior to enrollment)
• Willing to commit to traveling to the University of Minnesota every 6 months
• Written informed consent prior to the performance of any study related procedures

Exclusion Criteria:

• Previous administration of Laronidase enzyme > 3 months post transplantation
• Anticipated survival less than 2 years
• History of cardiac or pulmonary insufficiency, including an ejection fraction (EF) < 40% or those requiring continuous supplemental oxygen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Laronidase After Transplantation; Patients with Mucopolysaccharidosis type IH (MPS I, Hurler syndrome) treated with a prior allogeneic transplant >2 years previously and treated with Laronidase weekly for 2 years after transplant.	Drug: Laronidase; Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years; Other Names: Aldurazyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Adherence to the Scheduled Weekly Infusion by the Participants	To determine the feasibility of giving weekly Laronidase for 2 years in patients with Hurler syndrome after allogeneic transplantation, compliance throughout the study with drug administration, the percentage of adherence to the scheduled weekly infusion for each participant is measured.	24 months
Number of Participants Experiencing Severe Adverse Events	Number of participants experiencing severe adverse events that occur after administration with Laronidase to determine the feasibility of giving weekly Laronidase	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Growth Velocity	difference between baseline and month 24 growth velocities	Baseline, Month 24
Change in Muscle Strength	Handgrip strength is measured three times in both hands with a mechanical handheld Biodex System 3 dynamometer (Biodex medical Systems, Inc., Shirley, NY) with the subject in a seated position at each visit; the average for each hand is presented.	Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months
Change in Peak Heart Rate to Monitor "Fitness"	A modified Balke Treadmill Test was performed. Briefly, patients began walking at 2.0 mph with a 2% increase in grade every 2 min. A 12-lead electrocardiogram was monitored continuously throughout the test for the determination of heart rate and dysrhythmias or ischemic changes. Heart rate was measured at the end of each stage (i.e. every 2 min) .	Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months
Number of Participants Showing Improvements in Joint Range of Motion (ROM)	Bilateral shoulder flexion, elbow extension, and hip extension were measured using goniometry. Improvements are defined for all joints as >5°.	Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months
Shortening Fraction to Determine Systolic Cardiac Function	Cardiac ultrasounds were obtained at baseline and month 24. Two-dimensional imaging was obtained for determination of anatomy. Shortening fraction (SF [normal > 27%]) was calculated by standard methods to determine the normal systolic cardiac function	Baseline and month 24
Number of Participants With Changes in Cardiac Echo Structural Parameters	Pulse-wave and color Doppler interrogation of cardiac valves was performed for determination of valve regurgitation	Baseline and month 24
Correlation of 6 Minute Walk Test With Anti-laronidase Antibody + Status	6 minute walk test (6MWT) was performed to assess overall physical function and health status. In brief, a 30m hospital corridor marked by colored tape at each end was used. Subjects were instructed to walk from end to end at their self-selected pace, while attempting to cover as much distance as possible in the 6 min. The patients were instructed to walk around the mark as they changed direction. The time and distance covered was recorded, as was the heart rate prior to and immediately after completion of the walk test. To find the association between the rate of change in 6MWT, and anti drug antibody (ADA) titer, a statistical test is performed adjusting for age at the time of enrollment.	Assessed from baseline every 6 months through 2 years; change between baseline and 24 months reported.If baseline and/or 24-month data were not available, the longest interval between measurements was reported, with a minimum requirement of 12 months

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Publications and helpful links

General Publications

• Lund TC, Miller WP, Liao AY, Tolar J, Shanley R, Pasquali M, Sando N, Bigger BW, Polgreen LE, Orchard PJ. Post-transplant laronidase augmentation for children with Hurler syndrome: biochemical outcomes. Sci Rep. 2019 Oct 1;9(1):14105. doi: 10.1038/s41598-019-50595-1.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start (ACTUAL): May 29, 2012
• Primary Completion (ACTUAL): March 4, 2016
• Study Completion (ACTUAL): March 4, 2016

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (ESTIMATE): July 30, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: mucopolysaccharide IH (MPS IH)
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Syndrome; Mucopolysaccharidosis I
• Other Study ID Numbers: 2009LS090; MT2009-20 (OTHER: Blood and Marrow Transplantation Program); 1004M80513 (OTHER: IRB, University of Minnesota)