Hurler-Scheie Syndrome, Hurler Syndrome, Mucopolysaccharidosis I, Scheie Syndrome
Conditions
Keywords
MPS I Disease
Brief summary
This is a multi-center, open label, study conducted to evaluate the safety of laronidase administered by intravenous drip infusion in Japanese patients with MPS I disease. Following baseline evaluation, patients will receive weekly infusions of JC0498 at an intravenous dose of 100 units/kg. Patient safety will be monitored continuously throughout the trial. In addition, the effects of JC0498 treatment in this patient population will be assessed by periodically evaluating aspects of MPS I disease in patients at scheduled intervals over the duration of the trial. Since patients may be eligible for the trial if they have received JC0498, a portion of the data may be captured retrospectively and recorded onto the case report forms (CRFs). This study represents the first good clinical practice (GCP) effort to characterize MPS I in the Japanese population and evaluate the effects of JC0498 on disease manifestations.
Interventions
0.58 mg/kg every week
Sponsors
BioMarin/Genzyme LLC
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Written informed consent/assent of the patient or written informed consent of the parent(s) or the legal guardian(s), depending on the age of the patient, is required prior to any protocol-related procedures being performed; this includes information regarding hematopoietic stem cell transplantation (HSCT) in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative treatment for patients eligible for the trial and who have severe manifestations of MPS I with neurodegeneration. * Have a clinical diagnosis of MPS, confirmed by measurable clinical signs and symptoms of MPS I. * Have confirmed iduronidase deficiency with a leukocyte alpha-L-iduronidase enzyme activity level of less than 10.0% of the lower limit of the normal range of the measuring laboratory (SRL)
Exclusion criteria
* The patient is under consideration for or has previously undergone hematopoietic stem cell transplantation. * 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 (exception: JC0498). * The patient has known severe hypersensitivity to JC0498 or components of the delivery solution.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Evaluation | Up to 73 Weeks | Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Glycosaminoglycan (GAG) Excretion | Up to 73 Weeks | Percentage change in the concentration of GAG relative to creatinine in urine (ug GAG/mg creatinine) from baseline to last study visit. Greater decrease indicates greater response. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aldurazyme (Laronidase) Treatment Patients received weekly infusions of Aldurazyme (laronidase) at an intravenous dose of 100 Units/kg (0.58 mg/kg) body weight (labeled dose) for up to 73 weeks. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Aldurazyme (Laronidase) Treatment |
|---|---|
| Age, Continuous | 12.2 years STANDARD_DEVIATION 12.57 |
| Race/Ethnicity, Customized Asian (Japanese) | 3 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
Safety Evaluation
Overall Safety Summary of Adverse Events (AEs) during Treatment Safety assessment was based on the incidence of AE reports.
Time frame: Up to 73 Weeks
Population: The study enrolled eligible MPS I patients prior to marketing authorization in Japan. The analysis was intention to treat.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Having Adverse Events (AEs) | 3 participants |
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Having drug related AEs | 0 participants |
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Discontinuations due to AEs | 0 participants |
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Having Serious AEs | 1 participants |
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Having Severe AEs | 1 participants |
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Deaths | 0 participants |
| Aldurazyme (Laronidase) Treatment | Safety Evaluation | Having infusion-associated reactions | 0 participants |
Secondary
Urinary Glycosaminoglycan (GAG) Excretion
Percentage change in the concentration of GAG relative to creatinine in urine (ug GAG/mg creatinine) from baseline to last study visit. Greater decrease indicates greater response.
Time frame: Up to 73 Weeks
Population: The study enrolled eligible MPS I patients prior to marketing authorization in Japan. The analysis was intention to treat.\>~\* 1 patient final visit = Week 73; 1 patient final visit = Week 32; 1 patient final visit = Week 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 42 (1 patients analyzed) | -78.0 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 46 (1 patients analyzed) | -67.9 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Baseline (3 patients analyzed) | 0 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 4 (3 patients analyzed) | -68.0 percent change in concentration of GAG | Standard Deviation 12.76 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 8 (3 patients analyzed) | -69.9 percent change in concentration of GAG | Standard Deviation 7.98 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 12 (2 patients analyzed) | -74.6 percent change in concentration of GAG | Standard Deviation 11.47 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 16 (2 patients analyzed) | -71.0 percent change in concentration of GAG | Standard Deviation 9.4 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 20 (2 patients analyzed) | -60.6 percent change in concentration of GAG | Standard Deviation 12.85 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 26 (2 patients analyzed) | -71.5 percent change in concentration of GAG | Standard Deviation 5.84 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 30 (2 patients analyzed) | -75.2 percent change in concentration of GAG | Standard Deviation 10.65 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 34 (1 patients analyzed) | -77.7 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 38 (1 patients analyzed) | -69.9 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 52 (1 patients analyzed) | -77.0 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Week 64 (1 patients analyzed) | -81.1 percent change in concentration of GAG | Standard Deviation 0 |
| Aldurazyme (Laronidase) Treatment | Urinary Glycosaminoglycan (GAG) Excretion | Final Examination * (3 patients analyzed) | -69.7 percent change in concentration of GAG | Standard Deviation 20.23 |