Hurler-Scheie Syndrome, Hurler's Syndrome, Mucopolysaccharidosis I, Scheie Syndrome
Conditions
Brief 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).
Interventions
0.58 mg/kg every week
Sponsors
BioMarin/Genzyme LLC
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 26 in Liver Organ Volume | Baseline to 26 Weeks | A greater decrease in liver volume indicates a greater response. |
| Change From Baseline to Week 26 in Six Minute Walk Test (6MWT) | Baseline to 26 Weeks | Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response. |
Countries
Brazil, Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.58 mg/kg Aldurazyme Every Week 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. | 8 |
| 1.2 mg/kg Aldurazyme Every Week 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. | 9 |
| 1.2 mg/kg Aldurazyme Every 2 Weeks 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. | 8 |
| 1.8 mg/kg Aldurazyme Every 2 Weeks 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. | 9 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Non-compliant | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 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 |
|---|---|---|---|---|---|
| Age, Continuous | 8.7 years STANDARD_DEVIATION 5.34 | 8.5 years STANDARD_DEVIATION 4.86 | 8.0 years STANDARD_DEVIATION 6.64 | 9.1 years STANDARD_DEVIATION 4.97 | 9.3 years STANDARD_DEVIATION 5.48 |
| Sex: Female, Male Female | 18 Participants | 5 Participants | 4 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 16 Participants | 3 Participants | 5 Participants | 5 Participants | 3 Participants |
| Study Specific Race/Ethnicity Asian | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Study Specific Race/Ethnicity Black | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Study Specific Race/Ethnicity Caucasian | 21 participants | 4 participants | 6 participants | 5 participants | 6 participants |
| Study Specific Race/Ethnicity Hispanic | 3 participants | 1 participants | 0 participants | 1 participants | 1 participants |
| Study Specific Race/Ethnicity Other | 9 participants | 2 participants | 3 participants | 2 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 9 / 9 | 8 / 8 | 7 / 8 |
| serious Total, serious adverse events | 2 / 8 | 1 / 9 | 1 / 8 | 2 / 8 |
Outcome results
Primary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.58 mg/kg Aldurazyme Every Week | Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level | -57.57 Percentage of Change in GAG Level | 95% Confidence Interval 18.789 |
| 1.2 mg/kg Aldurazyme Every Week | Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level | -66.63 Percentage of Change in GAG Level | 95% Confidence Interval 14.917 |
| 1.2 mg/kg Aldurazyme Every 2 Weeks | Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level | -66.15 Percentage of Change in GAG Level | 95% Confidence Interval 8.043 |
| 1.8 mg/kg Aldurazyme Every 2 Weeks | Percent Change From Baseline to Week 26 in Urinary Glycosaminoglycan (GAG) Level | -62.66 Percentage of Change in GAG Level | 95% Confidence Interval 6.506 |
Secondary
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
Population: The analysis was intention to treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.58 mg/kg Aldurazyme Every Week | Change From Baseline to Week 26 in Six Minute Walk Test (6MWT) | 7.00 meters | 95% Confidence Interval 83.355 |
| 1.2 mg/kg Aldurazyme Every Week | Change From Baseline to Week 26 in Six Minute Walk Test (6MWT) | -12.17 meters | 95% Confidence Interval 58.043 |
| 1.2 mg/kg Aldurazyme Every 2 Weeks | Change From Baseline to Week 26 in Six Minute Walk Test (6MWT) | 25.43 meters | 95% Confidence Interval 75.496 |
| 1.8 mg/kg Aldurazyme Every 2 Weeks | Change From Baseline to Week 26 in Six Minute Walk Test (6MWT) | 52.14 meters | 95% Confidence Interval 72.804 |
Secondary
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
Population: The analysis was intention to treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.58 mg/kg Aldurazyme Every Week | Percent Change From Baseline to Week 26 in Liver Organ Volume | -26.27 Percentage of Change in Liver Volume | 95% Confidence Interval 7.85 |
| 1.2 mg/kg Aldurazyme Every Week | Percent Change From Baseline to Week 26 in Liver Organ Volume | -30.67 Percentage of Change in Liver Volume | 95% Confidence Interval 8.13 |
| 1.2 mg/kg Aldurazyme Every 2 Weeks | Percent Change From Baseline to Week 26 in Liver Organ Volume | -30.74 Percentage of Change in Liver Volume | 95% Confidence Interval 18.24 |
| 1.8 mg/kg Aldurazyme Every 2 Weeks | Percent Change From Baseline to Week 26 in Liver Organ Volume | -32.14 Percentage of Change in Liver Volume | 95% Confidence Interval 10.1 |