Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Laronidase

About this trial

This is an interventional treatment trial for Hurler Syndrome focused on measuring mucopolysaccharide IH (MPS IH)

Eligibility Criteria

undefined - 14 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Laronidase After Transplantation

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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

Secondary Outcome Measures

Changes in Growth Velocity

difference between baseline and month 24 growth velocities

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.

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) .

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°.

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

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

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.

Full Information

NCT ID

NCT01173016

First Posted

July 28, 2010

Last Updated

March 6, 2020

Sponsor

Masonic Cancer Center, University of Minnesota

1. Study Identification

Unique Protocol Identification Number

NCT01173016

Brief Title

Administration of IV Laronidase Post Bone Marrow Transplant in Hurler

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

May 29, 2012 (Actual)

Primary Completion Date

March 4, 2016 (Actual)

Study Completion Date

March 4, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hurler Syndrome

Keywords

mucopolysaccharide IH (MPS IH)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Laronidase After Transplantation

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Laronidase

Other Intervention Name(s)

Aldurazyme

Intervention Description

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

Primary Outcome Measure Information:

Title

Percentage of Adherence to the Scheduled Weekly Infusion by the Participants

Description

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.

Time Frame

24 months

Title

Number of Participants Experiencing Severe Adverse Events

Description

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

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Changes in Growth Velocity

Description

difference between baseline and month 24 growth velocities

Time Frame

Baseline, Month 24

Title

Change in Muscle Strength

Description

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.

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

Title

Change in Peak Heart Rate to Monitor "Fitness"

Description

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) .

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

Title

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

Description

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

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

Title

Shortening Fraction to Determine Systolic Cardiac Function

Description

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

Time Frame

Baseline and month 24

Title

Number of Participants With Changes in Cardiac Echo Structural Parameters

Description

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

Time Frame

Baseline and month 24

Title

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

Description

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.

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

10. Eligibility

Sex

All

Maximum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

No

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul Orchard, MD

Organizational Affiliation

Masonic Cancer Center, University of Minnesota

Official's Role

Principal Investigator

Facility Information:

Facility Name

Masonic Cancer Center, University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31575939

Citation

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.

Results Reference

derived

Links:

URL

https://www.nature.com/articles/s41390-019-0541-2

Description

Related Info

URL

https://www.nature.com/articles/s41598-019-50595-1#citeas

Description

Related Info

Hurler Syndrome

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial