CompletedNCT00144781Updated Apr 3, 2015Results posted

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

A Phase 4 interventional study of Aldurazyme (Recombinant Human Alpha-L-Iduronidase) and Aldurazyme (Recombinant Human Alpha-L-Iduronidase) in Mucopolysaccharidosis I, Hurler's Syndrome and Hurler-Scheie Syndrome, sponsored by Genzyme, a Sanofi Company. Completed at 5 sites in 2 countries. Per ClinicalTrials.gov, last updated 2015-04-03.

Sponsored by Genzyme, a Sanofi Company · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 34
Allocation: Randomized
Sex: All

Study 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).

Conditions studied

Mucopolysaccharidosis I
Hurler's Syndrome
Hurler-Scheie Syndrome
Scheie Syndrome

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In context

Mucopolysaccharidoses

145 studies on the registry are indexed under Mucopolysaccharidoses; 11 are open to participants now.

This study's enrollment of 34 is above the median of 15 across 80 interventional studies indexed under Mucopolysaccharidoses.

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Lead sponsor

Genzyme, a Sanofi Company is the lead sponsor of 303 studies on the registry; 5 are open to participants now.

Of its 24 completed or terminated interventional studies of FDA-regulated products, 19 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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).

Exclusion criteria

Exclusion Criteria:

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.

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 34 participants (actual)

Study arms

Active comparator
1
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.
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
Active comparator
2
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.
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
Active comparator
3
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.
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)
Active comparator
4
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.
Biological: Aldurazyme (Recombinant Human Alpha-L-Iduronidase)

Interventions

BiologicalAldurazyme (Recombinant Human Alpha-L-Iduronidase)
0.58 mg/kg every week
BiologicalAldurazyme (Recombinant Human Alpha-L-Iduronidase)
1.2 mg/kg every week
BiologicalAldurazyme (Recombinant Human Alpha-L-Iduronidase)
1.2 mg/kg every other week
BiologicalAldurazyme (Recombinant Human Alpha-L-Iduronidase)
1.8 mg/kg every other week

What researchers measure

Primary outcomes

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.
Time frame: Baseline to 26 Weeks

Secondary outcomes

Percent Change From Baseline to Week 26 in Liver Organ Volume
A greater decrease in liver volume indicates a greater response.
Time frame: 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.
Time frame: Baseline to 26 Weeks

Results

Posted Jun 16, 2009

Limitations and caveats

This study is limited by its small sample size and ability to detect small differences in urinary GAG levels between groups.

Participant flow

Participant flow — Overall Study
Milestone	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks
Started	8	9	8	9
Completed	8	7	8	9
Not completed	0	2	0	0
Withdrew: Adverse event	0	1	0	0
Withdrew: Non-compliant	0	1	0	0

Outcome measures

PrimaryPercent 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.

Time frame:: Baseline to 26 Weeks
Reported as:: Mean · Percentage of Change in GAG Level

Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level
Percentage of Change in GAG Level	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks
Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level	-57.57 ± 18.789	-66.63 ± 14.917	-66.15 ± 8.043	-62.66 ± 6.506

SecondaryPercent Change From Baseline to Week 26 in Liver Organ Volume

A greater decrease in liver volume indicates a greater response.

Time frame:: Baseline to 26 Weeks
Reported as:: Mean · Percentage of Change in Liver Volume

Percent Change From Baseline to Week 26 in Liver Organ Volume
Percentage of Change in Liver Volume	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks
Percent Change From Baseline to Week 26 in Liver Organ Volume	-26.27 ± 7.85	-30.67 ± 8.13	-30.74 ± 18.24	-32.14 ± 10.10

SecondaryChange 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.

Time frame:: Baseline to 26 Weeks
Reported as:: Mean · meters

Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)
meters	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks
Change From Baseline to Week 26 in Six Minute Walk Test (6MWT)	7.00 ± 83.355	-12.17 ± 58.043	25.43 ± 75.496	52.14 ± 72.804

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Aldurazyme\|Every Other\|Week 1.2 mg/kg*Check Title*	—	2/8 (25%)	8/8 (100%)
Aldurazyme\|Every Other\|Week 1.8 mg/kg*Check Title*	—	1/9 (11.1%)	9/9 (100%)
Aldurazyme\|Weekly\|0.58 mg/kg*Check Title*	—	1/8 (12.5%)	8/8 (100%)
Aldurazyme\|Weekly\|1.2 mg/kg*Check Title*	—	2/8 (25%)	7/8 (87.5%)

Most frequent serious events

Most frequent serious events
Event	Aldurazyme\|Every Other\|Week 1.2 mg/kg*Check Title*	Aldurazyme\|Every Other\|Week 1.8 mg/kg*Check Title*	Aldurazyme\|Weekly\|0.58 mg/kg*Check Title*	Aldurazyme\|Weekly\|1.2 mg/kg*Check Title*
AbasiaGeneral disorders	1/8	0/9	0/8	0/8
Acute sinusitisInfections and infestations	0/8	0/9	0/8	1/8
PneumoniaInfections and infestations	1/8	0/9	0/8	0/8
Femur fractureInjury, poisoning and procedural complications	0/8	0/9	1/8	0/8
Pulmonary oedemaRespiratory, thoracic and mediastinal disorders	1/8	0/9	0/8	0/8
Respiratory failureRespiratory, thoracic and mediastinal disorders	0/8	0/9	0/8	1/8
Abdominal distensionGastrointestinal disorders	0/8	1/9	0/8	0/8
Otitis media acuteInfections and infestations	0/8	1/9	0/8	0/8

Most frequent other events

Showing 10 of 157

Most frequent other events
Event	Aldurazyme\|Every Other\|Week 1.2 mg/kg*Check Title*	Aldurazyme\|Every Other\|Week 1.8 mg/kg*Check Title*	Aldurazyme\|Weekly\|0.58 mg/kg*Check Title*	Aldurazyme\|Weekly\|1.2 mg/kg*Check Title*
DiarrhoeaGastrointestinal disorders	4/8	3/9	6/8	6/8
VomitingGastrointestinal disorders	2/8	4/9	3/8	6/8
PyrexiaGeneral disorders	5/8	4/9	6/8	5/8
CoughRespiratory, thoracic and mediastinal disorders	1/8	2/9	5/8	5/8
NasopharyngitisInfections and infestations	3/8	5/9	2/8	1/8
Abdominal painGastrointestinal disorders	1/8	2/9	4/8	3/8
NauseaGastrointestinal disorders	0/8	1/9	4/8	4/8
SinusitisInfections and infestations	4/8	2/9	2/8	3/8
HeadacheNervous system disorders	2/8	0/9	2/8	4/8
Nasal congestionRespiratory, thoracic and mediastinal disorders	1/8	3/9	4/8	2/8

Baseline characteristics

Age, Continuous
Age, Continuous(years)	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks	Total
Mean	8.5 ± 4.86	8.0 ± 6.64	9.1 ± 4.97	9.3 ± 5.48	8.7 ± 5.34

Sex: Female, Male
Sex: Female, Male(Participants)	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks	Total
Female	5	4	3	6	18
Male	3	5	5	3	16

Study Specific Race/Ethnicity
Study Specific Race/Ethnicity(participants)	0.58 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every Week	1.2 mg/kg Aldurazyme Every 2 Weeks	1.8 mg/kg Aldurazyme Every 2 Weeks	Total
Caucasian	4	6	5	6	21
Black	1	0	0	0	1
Hispanic	1	0	1	1	3
Asian	0	0	0	0	0
Other	2	3	2	2	9

Study locations

5 sites

Hospital Infantil Joana de Gusmao
Florianopolis, Santa Catarina CEP 88025-601, Brazil
Universidade Federal de Minas Gerais
Belo Horizonte, CEP 30130-100, Brazil
Hospital de Clinical de Porto Alegre
Porto Alegre, CEP 90035-003, Brazil
Universidade Federal de Sao Paulo
San Paulo, CEP 04023-062, Brazil
Division of Clinical and Metabolic Genetics
Toronto, Ontario M5G 1X8, Canada

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 3, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00144781
Lead sponsor: Genzyme, a Sanofi Company
Collaborators: BioMarin/Genzyme LLC
First posted: Sep 5, 2005
Start date: Dec 2004
Primary completion: Jan 2006
Completion: Jan 2006
Results posted: Jun 16, 2009
Last update: Apr 3, 2015

Study contacts

Medical Information

study director · Genzyme, a Sanofi Company

View the source record on ClinicalTrials.gov ↗

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