Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00741338 | Immune Tolerance Study With Aldurazyme® (Laronidase) | PHASE1 | COMPLETED | 7 | — | — | Sep 1, 2008 | Sep 1, 2012 | Jul 2, 2014 | 2 | Brazil, Russia |
Immune tolerance induction success was defined as development of an anti-laronidase immunoglobulin G (IgG) antibody titer less than or equal to (\<=) 1:3200 after 24 weeks of receiving full-dose (0.58 mg/kg) laronidase therapy.
| Arm | Type | Description |
|---|---|---|
| Cohort 1 | EXPERIMENTAL | Tolerance Induction Period (TIP): Cyclosporine A (CsA) starting at 5 milligram per kilogram (mg/kg) orally three times daily until the target trough concentration of at least 350 nanogram per milliliter (ng/mL) (preferably 400 ng/mL) achieved along with azathioprine (Aza) 2.5 mg/kg/day orally. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly intravenous (IV) infusion (starting from Day 1) up to Week 12. CsA and Aza were gradually discontinued. Immune Challenge Period (ICP): following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 39. |
| Cohort 2 | EXPERIMENTAL | TIP: CsA starting at 6.7 mg/kg orally three times daily until the target trough concentration of at least 350 ng/mL (preferably 400 ng/mL) achieved along with Aza 5 mg/kg orally every other day. Once target CsA trough level achieved and maintained for at least 1 week, participants received laronidase 0.058 mg/kg (low-dose) once weekly IV infusion (starting from Day 1) up to Week 18. CsA and Aza were gradually discontinued. ICP: following TIP, laronidase dose increased to 0.12 mg/kg once weekly IV infusion for 1 week followed by 0.25 mg/kg once weekly IV infusion for 1 week and then 0.58 mg/kg (full-dose) once weekly IV infusion up to Week 45. |
| Name | Type | Description |
|---|---|---|
| Laronidase | BIOLOGICAL | 0.058 mg/kg - 0.58 mg/kg IV infusion weekly. |
| Cyclosporine A (CsA) | DRUG | Orally three times daily. |
| Azathioprine (Aza) | DRUG | Orally either every day for Cohort 1 or every other day for Cohort 2. |
Inclusion Criteria: * Written informed consent is required from the parent(s) or legal guardian(s) prior to any protocol-related procedures being performed. (A separate informed consent will be requested from the parent(s) for their genotyping, which is independent of the inclusion) * Participant's...