Mucopolysaccharidosis IPhase 4NCT00144781

A Dose-optimization Study of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I (MPS I) Disease

A Phase 4 study testing Aldurazyme (Recombinant Human Alpha-L-Iduronidase) in people with Mucopolysaccharidosis I and Hurler's Syndrome, run by Genzyme, a Sanofi Company at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The main purpose of this study is to evaluate differences in the pharmacodynamic response of 4 Aldurazyme® (laronidase) dose regimens in patients with Mucopolysaccharidosis I (MPS I). Read more about this study

Who is it for?: Any age
Conditions the study is for: Mucopolysaccharidosis I, Hurler's 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: 34 participants
Where: 5 sitesin 2 countries
Study dates: Dec 2004to Jan 2006
Phase: Phase 4
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Have a documented diagnosis of MPS I, confirmed by measurable clinical signs and symptoms of MPS I, and a documented fibroblast or leukocyte α-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.
Weigh at least 12.5 kg.
Have serum creatinine and blood urea nitrogen (BUN) values within age appropriate normal ranges.
Provide signed, written informed consent prior to any protocol-related procedures being performed. Consent of a legally authorized guardian(s) is (are) required for patients under 18 years. If the patient is under 18 years old and can understand the consent, written informed consent will be required from both the patient and the authorized guardian(s).

Who cannot join

Have previously received Aldurazyme® (laronidase).
Have a suspected hypersensitivity to Aldurazyme® (laronidase) or known hypersensitivity to components of the infusion solution.
Have previously undergone hematopoietic stem cell transplantation (HSCT; i.e., from bone marrow [BMT], peripheral blood, or umbilical cord blood) or other major organ transplantation.
Have a medical condition, serious inter-current illness, or other extenuating circumstance that may interfere with study compliance including all prescribed evaluations and follow-up activities, except the 6MWT. (Note: All patients may not be capable of performing the 6MWT due to age and/or maturity level. Exemption from performing the 6MWT must be obtained in writing by the investigator from the sponsor's medical monitor prior to enrollment).
Have an acute illness that requires surgical intervention, and/or anticipates surgery during study participation, and/or has had surgery within 30 days prior to study enrollment.
Have received an investigational drug within 30 days prior to study enrollment.
Is pregnant or lactating. Female patients of childbearing potential must have a negative pregnancy test [urine β-human chronic gonadotropin (hCG)] at entry (prior to the first infusion). Note: All female patients of childbearing potential and sexually mature males must be advised to use a medically accepted method of contraception throughout the study.

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

Brazil4 sites

Universidade Federal de Minas Gerais
Belo Horizonte, CEP 30130-100
Hospital Infantil Joana de Gusmao
Florianópolis, Santa Catarina, CEP 88025-601
Hospital de Clinical de Porto Alegre
Porto Alegre, CEP 90035-003
Universidade Federal de Sao Paulo
São Paulo, CEP 04023-062

Other trials in Brazil

Canada1 site

Division of Clinical and Metabolic Genetics
Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Multicenter, Multinational, Randomized, Dose-Optimization Study of the Safety and Pharmacodynamic Response of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I

The main purpose of this study is to evaluate differences in the pharmacodynamic response of 4 Aldurazyme® (laronidase) dose regimens in patients with Mucopolysaccharidosis I (MPS I).

Conditions: Mucopolysaccharidosis I, Hurler's Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome
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
0.58 mg/kg every week
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)Biological
1.2 mg/kg every week
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)Biological
1.2 mg/kg every other week
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)Biological
1.8 mg/kg every other week

Study groups in NCT00144781
Study group	Role	What they receive
1	Active comparator	0.58 mg Aldurazyme/kg of body weight (100 U/kg) administered every week (labeled dose). Final Visit is Week 27 for patients randomized to every week regimen. Receives: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
2	Active comparator	1.2 mg Aldurazyme/kg of body weight (200 U/kg) administered every week. Final Visit is Week 27 for patients randomized to every week regimen. Receives: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
3	Active comparator	1.2 mg Aldurazyme/kg of body weight (200 U/kg) administered every 2 weeks. Final Visit is Week 26 for patients randomized to every 2 week regimen. Receives: Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
4	Active comparator	1.8 mg Aldurazyme/kg of body weight (300 U/kg) administered every 2 weeks. Final Visit is Week 26 for patients randomized to every 2 week regimen. 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.

Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level
Urinary GAG Level - Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.
Measured: Baseline to 26 Weeks

Secondary outcomes (2)

Percent Change From Baseline to Week 26 in Liver Organ Volume
A greater decrease in liver volume indicates a greater response.
Measured: Baseline to 26 Weeks
Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)
Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.
Measured: Baseline to 26 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2004Jan 2006

First posted5 Sep 2005 (estimated)
Study startDec 2004
Primary completionJan 2006
Study completionJan 2006

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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00144781
Sponsor's protocol ID: ALID-017-03
Status last verified: Mar 2015
First submitted: 2 Sep 2005
Last updated: 3 Apr 2015
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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

All Mucopolysaccharidosis I trials

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 Multicenter, Multinational, Randomized, Dose-Optimization Study of the Safety and Pharmacodynamic Response of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I
ClinicalTrials.gov ID: NCT00144781
Acronym / sponsor ID: ALID-017-03
Conditions: Mucopolysaccharidosis I, Hurler's Syndrome, Hurler-Scheie Syndrome, Scheie Syndrome
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
Collaborators: BioMarin/Genzyme LLC
Study start: Dec 2004
Primary completion: Jan 2006 (actual)
Study completion: Jan 2006 (actual)
First posted: 5 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 purpose of this study is to evaluate differences in the pharmacodynamic response of 4 Aldurazyme® (laronidase) dose regimens in patients with Mucopolysaccharidosis I (MPS I).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
1	Active comparator	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)0.58 mg Aldurazyme/kg of body weight (100 U/kg) administered every week (labeled dose). Final Visit is Week 27 for patients randomized to every week regimen.
2	Active comparator	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)1.2 mg Aldurazyme/kg of body weight (200 U/kg) administered every week. Final Visit is Week 27 for patients randomized to every week regimen.
3	Active comparator	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)1.2 mg Aldurazyme/kg of body weight (200 U/kg) administered every 2 weeks. Final Visit is Week 26 for patients randomized to every 2 week regimen.
4	Active comparator	Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)1.8 mg Aldurazyme/kg of body weight (300 U/kg) administered every 2 weeks. Final Visit is Week 26 for patients randomized to every 2 week regimen.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

Have a documented diagnosis of MPS I, confirmed by measurable clinical signs and symptoms of MPS I, and a documented fibroblast or leukocyte α-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range of the measuring laboratory.
Weigh at least 12.5 kg.
Have serum creatinine and blood urea nitrogen (BUN) values within age appropriate normal ranges.
Provide signed, written informed consent prior to any protocol-related procedures being performed. Consent of a legally authorized guardian(s) is (are) required for patients under 18 years. If the patient is under 18 years old and can understand the consent, written informed consent will be required from both the patient and the authorized guardian(s).

Key exclusion criteria (7 listed)

Have previously received Aldurazyme® (laronidase).
Have a suspected hypersensitivity to Aldurazyme® (laronidase) or known hypersensitivity to components of the infusion solution.
Have previously undergone hematopoietic stem cell transplantation (HSCT; i.e., from bone marrow [BMT], peripheral blood, or umbilical cord blood) or other major organ transplantation.
Have a medical condition, serious inter-current illness, or other extenuating circumstance that may interfere with study compliance including all prescribed evaluations and follow-up activities, except the 6MWT. (Note: All patients may not be capable of performing the 6MWT due to age and/or maturity level. Exemption from performing the 6MWT must be obtained in writing by the investigator from the sponsor's medical monitor prior to enrollment).
Have an acute illness that requires surgical intervention, and/or anticipates surgery during study participation, and/or has had surgery within 30 days prior to study enrollment.

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)0.58 mg/kg every week	Biological	1
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)1.2 mg/kg every week	Biological	2
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)1.2 mg/kg every other week	Biological	3
Aldurazyme (Recombinant Human Alpha-L-Iduronidase)1.8 mg/kg every other week	Biological	4

Primary outcome

Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level
Time frame: Baseline to 26 Weeks
Urinary GAG Level - Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.

2 secondary outcomes

Percent Change From Baseline to Week 26 in Liver Organ Volume
Time frame: Baseline to 26 Weeks
Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)
Time frame: Baseline to 26 Weeks

Results and safety

Results posted to the registry on 16 Jun 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
0.58 mg/kg Aldurazyme Every Week	8	8
1.2 mg/kg Aldurazyme Every Week	9	7
1.2 mg/kg Aldurazyme Every 2 Weeks	8	8
1.8 mg/kg Aldurazyme Every 2 Weeks	9	9

Primary outcome: Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level

Time frame: Baseline to 26 Weeks. Mean (95% Confidence Interval). Unit: Percentage of Change in GAG Level

Measure	0.58 mg/kg Aldurazyme Every Week n = 8	1.2 mg/kg Aldurazyme Every Week n = 7	1.2 mg/kg Aldurazyme Every 2 Weeks n = 8	1.8 mg/kg Aldurazyme Every 2 Weeks n = 9
Value	-57.57 (18.789)	-66.63 (14.917)	-66.15 (8.043)	-62.66 (6.506)

Population analysed: Based on the changes in urinary GAG levels observed in the Phase 3 double-blind study, a sample size of 8 patients per group would have sufficient power to detect a 29 percentage point difference between groups in the mean change in urinary GAG levels as being statistically significant. The analysis was intention to treat.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aldurazyme\|Every Other\|Week 1.2 mg/kg*Check Title*	2 of 8 (25%)	8 of 8 (100%)	Not reported
Aldurazyme\|Every Other\|Week 1.8 mg/kg*Check Title*	1 of 9 (11.1%)	9 of 9 (100%)	Not reported
Aldurazyme\|Weekly\|0.58 mg/kg*Check Title*	1 of 8 (12.5%)	8 of 8 (100%)	Not reported
Aldurazyme\|Weekly\|1.2 mg/kg*Check Title*	2 of 8 (25%)	7 of 8 (87.5%)	Not reported

Limitations and caveats (from the sponsor): This study is limited by its small sample size and ability to detect small differences in urinary GAG levels between groups.

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 Information study director

Genzyme, a Sanofi Company

5 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Aldurazyme (Recombinant Human Alpha-L-Iduronidase) in people with Mucopolysaccharidosis I and Hurler's Syndrome, run by Genzyme, a Sanofi Company at 5 sites in 2 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 4 inclusion and 7 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 5 sites in Brazil, Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level (time frame: Baseline to 26 Weeks). 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 NCT00144781.

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.