Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Hurler Syndrome

Intervention / Treatment
-----------------
* Drug: Laronidase


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Maximum Age: 14 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laronidase After Transplantation<br>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<br>* Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mucopolysaccharide IH (MPS IH)