Skip to main content
OpenTrials
Completed

NCT Number: NCT01173016

Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hurler Syndrome Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis I Nutritional and Metabolic Diseases Skin and Connective Tissue Diseases

Age range

Up to 14 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

laronidase

Drug

Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years

Other names: Aldurazyme

Primary outcomes

  1. Percentage of Adherence to the Scheduled Weekly Infusion by the Participants

    Time frame: 24 months

    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.

  2. Number of Participants Experiencing Severe Adverse Events

    Time frame: 24 months

    Number of participants experiencing severe adverse events that occur after administration with Laronidase to determine the feasibility of giving weekly Laronidase

Secondary outcomes

  1. Changes in Growth Velocity

    Time frame: Baseline, Month 24

    difference between baseline and month 24 growth velocities

  2. Change in Muscle Strength

    Time frame: 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

    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.

  3. Change in Peak Heart Rate to Monitor "Fitness"

    Time frame: 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

    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) .

  4. Number of Participants Showing Improvements in Joint Range of Motion (ROM)

    Time frame: 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

    Bilateral shoulder flexion, elbow extension, and hip extension were measured using goniometry. Improvements are defined for all joints as >5°.

  5. Shortening Fraction to Determine Systolic Cardiac Function

    Time frame: Baseline and month 24

    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

  6. Number of Participants With Changes in Cardiac Echo Structural Parameters

    Time frame: Baseline and month 24

    Pulse-wave and color Doppler interrogation of cardiac valves was performed for determination of valve regurgitation

  7. Correlation of 6 Minute Walk Test With Anti-laronidase Antibody + Status

    Time frame: 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

    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.

Sponsors and collaborators

Lead sponsor

Masonic Cancer Center, University of Minnesota

Other

Registry information

Official study title

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

Important dates

Study start
2012
Primary completion
2016
Study completion
2016
First posted
Jul 30, 2010
Registry last updated
Mar 20, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.