Hurler SyndromePhase 1NCT01173016
Administration of IV Laronidase Post Bone Marrow Transplant in Hurler
A Phase 1 study testing Laronidase in people with Hurler Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 14 years
- Conditions the study is for
- Hurler Syndrome
- What is being tested?
- Laronidase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2012to 4 Mar 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: 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.
Read the 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.
- Conditions
- Hurler Syndrome
- Being tested
- Laronidase
- Keywords
- mucopolysaccharide IH (MPS IH)
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LaronidaseDrug
Also called Aldurazyme
Laronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years
| Study group | Role | What they receive |
|---|---|---|
| Laronidase After Transplantation | Experimental | 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. Receives: Drug: Laronidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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
Measured: 24 months
Secondary outcomes (7)
Changes in Growth Velocity
difference between baseline and month 24 growth velocities
Measured: 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.
Measured: 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) .
Measured: 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°.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2010 (estimated)
- Study start29 May 2012
- Primary completion4 Mar 2016
- Study completion4 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hurler SyndromeStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Orchard, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01173016
- Sponsor's protocol ID
- 2009LS090
- Other IDs
- MT2009-20, 1004M80513
- Status last verified
- Mar 2020
- First submitted
- 28 Jul 2010
- Last updated
- 20 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 31575939
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Administration of Intravenous Laronidase Following Allogeneic Transplantation for Hurler Syndrome
- ClinicalTrials.gov ID
- NCT01173016
- Acronym / sponsor ID
- 2009LS090
- Conditions
- Hurler Syndrome
- Keywords
- mucopolysaccharide IH (MPS IH)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 29 May 2012 (actual)
- Primary completion
- 4 Mar 2016 (actual)
- Study completion
- 4 Mar 2016 (actual)
- First posted
- 30 Jul 2010 (estimated)
- Results
- Posted 20 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Laronidase After Transplantation | Experimental | Drug: LaronidasePatients 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. |
Who may qualify
- Ages
- Up to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LaronidaseAlso: AldurazymeLaronidase 0.58 mg/kg intravenously (IV) once a week for a maximum of 2 years | Drug | Laronidase After Transplantation |
Primary outcome
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.
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
7 secondary outcomes
Changes in Growth Velocity
Time frame: Baseline, Month 24
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
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
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
Shortening Fraction to Determine Systolic Cardiac Function
Time frame: Baseline and month 24
Number of Participants With Changes in Cardiac Echo Structural Parameters
Time frame: Baseline and month 24
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31575939Lund 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
Related trials for Hurler Syndrome
Active, not recruitingObservational study
Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.
Hematopoietic Cell Transplantation, Mucopolysaccharidosis Type I
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
RecruitingPhase 1
ISP-001: Sleeping Beauty Transposon-Engineered B Cells for MPS I
Mucopolysaccharidosis IH/S, Mucopolysaccharidosis IS
Active, not recruitingPhase 1/2
Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant
Mucopolysaccharidosis IH
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Orchard, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Laronidase in people with Hurler Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Adherence to the Scheduled Weekly Infusion by the Participants (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01173016, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2020.