Hurler-Scheie Syndrome, Hurler's Syndrome, Mucopolysaccharidosis I, Scheie Syndrome
Conditions
Brief summary
This study is being conducted to collect additional long-term efficacy and safety data of Aldurazyme® (laronidase) patients with MPS I disease. Patients who were previously enrolled in the Phase 3 Double-Blind Study will be enrolled in this study.
Interventions
BIOLOGICALAldurazyme
Placebo for 26 weeks then 0.58 mg/kg Aldurazyme every week for 182 weeks
BIOLOGICALplacebo
Placebo for 26 weeks
Sponsors
BioMarin/Genzyme LLC
Genzyme, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* The patient or patient's legal guardian must provide written informed consent prior to any protocol-related procedures being performed. * The patient must have successfully completed Study ALID-003-99 (who received 21 of 26 consecutive weekly infusions). * The patient has not experienced any safety issues that would contraindicate participation in the Extension study. * A female patient of childbearing potential must have a negative pregnancy test at entry
Exclusion criteria
* The patient is pregnant or lactating. * The patient has received an investigational drug within 30 days prior to the study enrollment. * The patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly interfere with study compliance including all prescribed evaluations and follow-up activities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Baseline to Week 182 | Percent Predicted Forced Vital Capacity: the maximal exhaled breath volume following a maximal inhaled breath. Overall change from Baseline to Week 182 in percent predicted FVC = (observed value)/(predicted value) \* 100%). A higher value indicates a greater response. |
| Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Baseline to Week 182 | Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Baseline to Week 182 | CHAQ/HAQ = Patient questionnaire that measures the degree of disability on a scale of 0 (no disability) to 3 (maximal disability). A lower score indicates a greater response. |
| Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Baseline to Week 182 | Apnea/Hypopnea Index (AHI): Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. A greater decrease in events indicates a greater response. |
| Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Baseline to Week182 | Active Joint Range of Motion (ROM): Shoulder Flexion Ability to maximally raise one's arm overhead without assistance. Shoulder range of motion (mean of left and right arms) measured in degrees (0-180) by goniometry. Greater degree of flexion indicates greater response. |
| Change From Baseline to Week 182 in Liver Volume | Baseline to Week 182 | Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 182 in Urinary GAG Level | Baseline to Week 182 | Urinary Glycosaminoglycan (GAG) Levels: \>\> Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response. |
Countries
Brazil, Canada, Germany, Italy, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Aldurazyme Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. | 23 |
| Aldurazyme/Aldurazyme Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. | 22 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Aldurazyme/Aldurazyme | Placebo/Aldurazyme |
|---|---|---|---|
| Age, Continuous | 15.5 years STANDARD_DEVIATION 8.04 | 15.6 years STANDARD_DEVIATION 8.63 | 15.4 years STANDARD_DEVIATION 7.63 |
| Age, Customized <=12 years | 22 participants | 12 participants | 10 participants |
| Age, Customized 13 to <= 18 years | 11 participants | 3 participants | 8 participants |
| Age, Customized 19 to <= 65 years | 12 participants | 7 participants | 5 participants |
| Race/Ethnicity Asian | 2 participants | 1 participants | 1 participants |
| Race/Ethnicity Black | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity Caucasian | 37 participants | 16 participants | 21 participants |
| Race/Ethnicity Hispanic | 4 participants | 4 participants | 0 participants |
| Race/Ethnicity Other | 2 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 23 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Male | 22 Participants | 11 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 23 | 22 / 22 |
| serious Total, serious adverse events | 11 / 23 | 14 / 22 |
Outcome results
Primary
Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC)
Percent Predicted Forced Vital Capacity: the maximal exhaled breath volume following a maximal inhaled breath. Overall change from Baseline to Week 182 in percent predicted FVC = (observed value)/(predicted value) \* 100%). A higher value indicates a greater response.
Time frame: Baseline to Week 182
Population: This study enrolled patients who completed the Phase 3 Double-Blind Study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat with last value carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Baseline percentage points FVC | 51.0 percent predicted FVC | Standard Deviation 13.15 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Week 182 percentage points FVC | 47.7 percent predicted FVC | Standard Deviation 13.69 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Overall Change from Baseline to Week 182 | -3.3 percent predicted FVC | Standard Deviation 9.07 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Baseline percentage points FVC | 48.4 percent predicted FVC | Standard Deviation 14.85 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Week 182 percentage points FVC | 47.2 percent predicted FVC | Standard Deviation 15.24 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC) | Overall Change from Baseline to Week 182 | -1.2 percent predicted FVC | Standard Deviation 6.52 |
Primary
Change From Baseline to Week 182 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 Week 182
Population: The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat with last value carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Baseline distance walked | 348.3 Meters | Standard Deviation 128.81 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Week 182 distance walked | 367.7 Meters | Standard Deviation 151.25 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Overall Change from Baseline to Week 182 | 19.4 Meters | Standard Deviation 107.36 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Baseline distance walked | 319.0 Meters | Standard Deviation 131.41 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Week 182 distance walked | 358.3 Meters | Standard Deviation 126.4 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Six Minute Walk Test (6MWT) | Overall Change from Baseline to Week 182 | 39.2 Meters | Standard Deviation 85.84 |
Secondary
Change From Baseline to Week 182 in Active Joint Range of Motion (ROM)
Active Joint Range of Motion (ROM): Shoulder Flexion Ability to maximally raise one's arm overhead without assistance. Shoulder range of motion (mean of left and right arms) measured in degrees (0-180) by goniometry. Greater degree of flexion indicates greater response.
Time frame: Baseline to Week182
Population: The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Baseline degrees | 85.2 Degrees | Standard Deviation 32.66 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Week 182 degrees | 103.5 Degrees | Standard Deviation 23.34 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Overall change from Baseline to Week 182 | 18.3 Degrees | Standard Deviation 21.59 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Baseline degrees | 96.1 Degrees | Standard Deviation 30.25 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Week 182 degrees | 109.2 Degrees | Standard Deviation 22.24 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Active Joint Range of Motion (ROM) | Overall change from Baseline to Week 182 | 13.1 Degrees | Standard Deviation 20.66 |
Secondary
Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI)
Apnea/Hypopnea Index (AHI): Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. A greater decrease in events indicates a greater response.
Time frame: Baseline to Week 182
Population: The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Overall Change from Baseline to Week 182 | -4.8 Events per Hour | Standard Deviation 13.86 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Baseline events per hour | 14.6 Events per Hour | Standard Deviation 12.9 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Week 182 events per hour | 9.8 Events per Hour | Standard Deviation 14.6 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Week 182 events per hour | 14.0 Events per Hour | Standard Deviation 19.32 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Overall Change from Baseline to Week 182 | -4.0 Events per Hour | Standard Deviation 12.91 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI) | Baseline events per hour | 18.0 Events per Hour | Standard Deviation 15.54 |
Secondary
Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score
CHAQ/HAQ = Patient questionnaire that measures the degree of disability on a scale of 0 (no disability) to 3 (maximal disability). A lower score indicates a greater response.
Time frame: Baseline to Week 182
Population: The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Baseline Score | 1.75 Units on a scale | Standard Deviation 0.74 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Week 182 Score | 1.49 Units on a scale | Standard Deviation 0.768 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Overall change from Baseline to Week 182 | -0.26 Units on a scale | Standard Deviation 0.688 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Baseline Score | 1.99 Units on a scale | Standard Deviation 0.496 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Week 182 Score | 1.56 Units on a scale | Standard Deviation 0.758 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score | Overall change from Baseline to Week 182 | -0.43 Units on a scale | Standard Deviation 0.574 |
Secondary
Change From Baseline to Week 182 in Liver Volume
Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
Time frame: Baseline to Week 182
Population: The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Liver Volume | Baseline liver volume (cm3) | 1351.6 Cubic centimeters (cm3) | Standard Deviation 323.71 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Liver Volume | Week 182 liver volume (cm3) | 1079.9 Cubic centimeters (cm3) | Standard Deviation 256.99 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Liver Volume | Percent Change from Baseline to Week 182 (%) | -17.6 Cubic centimeters (cm3) | Standard Deviation 20.21 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Liver Volume | Baseline liver volume (cm3) | 1228.5 Cubic centimeters (cm3) | Standard Deviation 279.62 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Liver Volume | Week 182 liver volume (cm3) | 1001.4 Cubic centimeters (cm3) | Standard Deviation 157.23 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Liver Volume | Percent Change from Baseline to Week 182 (%) | -16.1 Cubic centimeters (cm3) | Standard Deviation 14.76 |
Other Pre-specified
Change From Baseline to Week 182 in Urinary GAG Level
Urinary Glycosaminoglycan (GAG) Levels: \>\> Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.
Time frame: Baseline to Week 182
Population: The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Urinary GAG Level | Baseline level (ug GAG/mg Creatinine) | 250.2 ug GAG/mg Creatinine | Standard Deviation 105.09 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Urinary GAG Level | Week 182 level (ug GAG/mg Creatinine) | 55.3 ug GAG/mg Creatinine | Standard Deviation 30.88 |
| Placebo/Aldurazyme | Change From Baseline to Week 182 in Urinary GAG Level | Percent change from Baseline to Week 182 (%) | -77.0 ug GAG/mg Creatinine | Standard Deviation 10.09 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Urinary GAG Level | Baseline level (ug GAG/mg Creatinine) | 190.2 ug GAG/mg Creatinine | Standard Deviation 59.81 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Urinary GAG Level | Week 182 level (ug GAG/mg Creatinine) | 59.8 ug GAG/mg Creatinine | Standard Deviation 34.99 |
| Aldurazyme/Aldurazyme | Change From Baseline to Week 182 in Urinary GAG Level | Percent change from Baseline to Week 182 (%) | -66.3 ug GAG/mg Creatinine | Standard Deviation 21.29 |