Mucopolysaccharidosis IPhase 2NCT00146757
A Study Evaluating the Safety and Pharmacokinetics of Aldurazyme® (Laronidase) in MPS I Patients Less Than 5 Years Old
A Phase 2 study testing Aldurazyme (Recombinant Human Alpha-L-Iduronidase) in people with Mucopolysaccharidosis I and Hurler Syndrome, run by Genzyme, a Sanofi Company at 4 sites in 4 countries.
Trial summary
The main objectives of this study are to evaluate the safety and pharmacokinetics (PK) of enzyme replacement therapy with recombinant human alpha-L-iduronidase [Aldurazyme® (laronidase)] in mucopolysaccharidosis I (MPS I) patients less than 5 years old. Efficacy measurements will also be evaluated in this study. Read more about this study
- Who is it for?
- Ages Up to 5 years
- Conditions the study is for
- Mucopolysaccharidosis I, Hurler Syndrome, Hurler-Scheie Syndrome
- What is being tested?
- Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Oct 2002to May 2005
- Phase
- Phase 2
- 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 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion.)
- Be less than 5 years of age at the time of enrollment.
- Have confirmed iduronidase deficiency with a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0 % of the lower limit of the normal range, or below the detection range of the measuring laboratory.
- Have a clinical diagnosis of MPS I based on genotyping.
- Documentation in his/her medical record that the parent(s) or legal guardian(s) have had counseling or a consultation regarding HSCT in order to assure that the parent(s) or legal guardian(s) are fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and with the severe manifestations of MPS I with neurodegeneration.
Who cannot join
- The patient is under consideration for or has undergone hematopoietic stem cell transplantation (HSCT).
- The patient has acute hydrocephalus at the time of enrollment.
- The patient has a clinically significant organic disease (with the exception of symptoms relating to MPS I) including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival.
- The patient has received any investigational product within 30 days prior to trial enrollment.
- The patient has known severe hypersensitivity to Aldurazyme® (laronidase) or components of the delivery solution.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
United Kingdom1 site
Willink Biochemical Genetics Unit Royal Hospital for Children
Manchester
About this study
Official title: A Phase II Open-Label Clinical Trial of Recombinant Human Alpha-L-iduronidase (Aldurazyme®) to Evaluate the Safety and Pharmacokinetics in Mucopolysaccharidosis I (MPS I) Patients Less Than 5 Years Old
The main objectives of this study are to evaluate the safety and pharmacokinetics (PK) of enzyme replacement therapy with recombinant human alpha-L-iduronidase [Aldurazyme® (laronidase)] in mucopolysaccharidosis I (MPS I) patients less than 5 years old. Efficacy measurements will also be evaluated in this study.
- Being tested
- Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)Biological
100 U/kg every week
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)Biological
200 U/kg every week (Week 26 onwards)
| Study group | Role | What they receive |
|---|---|---|
| Aldurazyme (rhIDU) 100 U/kg ONLY every week | Experimental | Patients received Aldurazyme (recombinant human alpha-L-iduronidase (rhIDU)) once per week at a dose of 100 Units/kg (approximately 0.58 mg/kg) for up to 52 weeks - labeled dose. Receives: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase) |
| Aldurazyme (rhIDU) 100-200 U/kg every week | Experimental | After receiving 100 Units/kg dose of Aldurazyme (rhIDU) for the first 25 weeks, patients enrolling after January 1, 2004 were eligible to receive an increased dose of 200 Units/kg from Week 26 onwards if the patient's urinary glycosaminoglycan (uGAG) levels were >200µg/mg creatinine at Week 22. Receives: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Evaluation
Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports.
Measured: 52 weeks
Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞)
AUC∞ is a measure of the total exposure to a drug.
Measured: 52 weeks
Pharmacokinetics - Elimination Half Life (t1/2)
Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.
Measured: 52 weeks
Pharmacokinetics - Total Plasma Clearance (CL)
CL is volume of the body fluid cleared of the drug per unit of time.
Measured: 52 weeks
Pharmacokinetics - Volume of Distribution (Vz)
Vz is the volume that relates the amount of drug in the body after absorption is complete to the concentration of drug in the plasma.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2005 (estimated)
- Study startOct 2002
- Primary completionMay 2005
- Study completionMay 2005
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.
- Other trials for Mucopolysaccharidosis IStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- BioMarin/Genzyme LLC
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00146757
- Sponsor's protocol ID
- ALID-014-02
- Status last verified
- Mar 2015
- First submitted
- 2 Sep 2005
- Last updated
- 3 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label Clinical Trial of Recombinant Human Alpha-L-iduronidase (Aldurazyme®) to Evaluate the Safety and Pharmacokinetics in Mucopolysaccharidosis I (MPS I) Patients Less Than 5 Years Old
- ClinicalTrials.gov ID
- NCT00146757
- Acronym / sponsor ID
- ALID-014-02
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Collaborators
- BioMarin/Genzyme LLC
- Study start
- Oct 2002
- Primary completion
- May 2005 (actual)
- Study completion
- May 2005 (actual)
- First posted
- 7 Sep 2005 (estimated)
- Results
- Posted 16 Jun 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objectives of this study are to evaluate the safety and pharmacokinetics (PK) of enzyme replacement therapy with recombinant human alpha-L-iduronidase [Aldurazyme® (laronidase)] in mucopolysaccharidosis I (MPS I) patients less than 5 years old. Efficacy measurements will also be evaluated in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aldurazyme (rhIDU) 100 U/kg ONLY every week | Experimental | Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)Patients received Aldurazyme (recombinant human alpha-L-iduronidase (rhIDU)) once per week at a dose of 100 Units/kg (approximately 0.58 mg/kg) for up to 52 weeks - labeled dose. |
| Aldurazyme (rhIDU) 100-200 U/kg every week | Experimental | Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)After receiving 100 Units/kg dose of Aldurazyme (rhIDU) for the first 25 weeks, patients enrolling after January 1, 2004 were eligible to receive an increased dose of 200 Units/kg from Week 26 onwards if the patient's urinary glycosaminoglycan (uGAG) levels were >200µg/mg creatinine at Week 22. |
Who may qualify
- Ages
- Up to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion.)
- Be less than 5 years of age at the time of enrollment.
- Have confirmed iduronidase deficiency with a fibroblast or leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0 % of the lower limit of the normal range, or below the detection range of the measuring laboratory.
- Have a clinical diagnosis of MPS I based on genotyping.
- Documentation in his/her medical record that the parent(s) or legal guardian(s) have had counseling or a consultation regarding HSCT in order to assure that the parent(s) or legal guardian(s) are fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and with the severe manifestations of MPS I with neurodegeneration.
Key exclusion criteria (5 listed)
- The patient is under consideration for or has undergone hematopoietic stem cell transplantation (HSCT).
- The patient has acute hydrocephalus at the time of enrollment.
- The patient has a clinically significant organic disease (with the exception of symptoms relating to MPS I) including: cardiovascular, hepatic, pulmonary, neurologic, or renal disease, other serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival.
- The patient has received any investigational product within 30 days prior to trial enrollment.
- The patient has known severe hypersensitivity to Aldurazyme® (laronidase) or components of the delivery solution.
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 |
|---|---|---|
| Aldurazyme (Recombinant Human Alpha-L-Iduronidase)100 U/kg every week | Biological | Aldurazyme (rhIDU) 100 U/kg ONLY every week |
| Aldurazyme (Recombinant Human Alpha-L-Iduronidase)200 U/kg every week (Week 26 onwards) | Biological | Aldurazyme (rhIDU) 100-200 U/kg every week |
Primary outcome
Safety Evaluation
Time frame: 52 weeks
Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports.
Pharmacokinetics - Area Under the (Plasma Concentration-time) Curve (AUC∞)
Time frame: 52 weeks
AUC∞ is a measure of the total exposure to a drug.
Pharmacokinetics - Elimination Half Life (t1/2)
Time frame: 52 weeks
Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.
Pharmacokinetics - Total Plasma Clearance (CL)
Time frame: 52 weeks
CL is volume of the body fluid cleared of the drug per unit of time.
Pharmacokinetics - Volume of Distribution (Vz)
Time frame: 52 weeks
Vz is the volume that relates the amount of drug in the body after absorption is complete to the concentration of drug in the plasma.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Mucopolysaccharidosis I
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
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
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.
Medical Monitor study director
Genzyme, a Sanofi Company
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aldurazyme (Recombinant Human Alpha-L-Iduronidase) in people with Mucopolysaccharidosis I and Hurler Syndrome, run by Genzyme, a Sanofi Company at 4 sites in 4 countries.
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 5 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 3 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, Germany, Netherlands, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Jun 2009). 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?
Safety Evaluation (time frame: 52 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Apr 2015.