Clinical trial NCT01173016: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hurler Syndrome
Keywords: mucopolysaccharide IH (MPS IH)
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2010-07-30
Enrollment: 11
Sex: ALL
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Adherence to the Scheduled Weekly Infusion by the Participants
timeFrame: 24 months
measure: Number of Participants Experiencing Severe Adverse Events
timeFrame: 24 months
Secondary outcomes:
measure: Changes in Growth Velocity
timeFrame: Baseline, Month 24
measure: Change in Muscle Strength
timeFrame: 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
measure: Change in Peak Heart Rate to Monitor "Fitness"
timeFrame: 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
measure: Number of Participants Showing Improvements in Joint Range of Motion (ROM)
timeFrame: 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
measure: Shortening Fraction to Determine Systolic Cardiac Function
timeFrame: Baseline and month 24
measure: Number of Participants With Changes in Cardiac Echo Structural Parameters
timeFrame: Baseline and month 24
measure: Correlation of 6 Minute Walk Test With Anti-laronidase Antibody + Status
timeFrame: 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
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Paul Orchard, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.