Clinical Trials
Hunterase ICV (intracerebroventricular idursulfase-β) was well tolerated, reduced the heparan sulfate concentration in the cerebrospinal fluid, and was effective at preventing and stabilizing developmental decline in patients with neuronopathic MPS II.
Phase I/II clinical study aimed to evaluate the efficacy and safety of intracerebroventicular idursulfase-β in patients with mucopolysaccharidosis II (MPS II).
The open-label, phase I/II study was conducted in 6 patients aged 23-65 months with severe MPS II and significant developmental delay using the historical control group at two clinical sites in Japan.
A placebo control was not considered because of an unacceptable risk/benefit ratio as with device placement and ICV administration of an inactive comparator.
All patients had tolerated ≥24 weeks of treatment with intravenous idursulfase before the start of the study.
Intracerebroventricular Idursulfase-β (increasing from 1 to 30 mg between weeks 0 and 24, followed by a 30-mg final dose) was administered once every 4 weeks using an implanted CSF reservoir.
Intravenous administration of idursulfase was also continued throughout the study.
Primary Endpoint and Result
Primary endpoint
Heparan sulfate (HS) concentration in the cerebrospinal fluid (CSF).
Results
HS concentrations in the CSF decreased (40% - 80%) from baseline to week 100 in all patients following ICV idursulfase-β administration.
Change in HS in the CSF of patients with MPS II from the start of idursulfase-β treatment up to week 100
HS concentrations in CSF (µg/mL)
Ratio of each HS concentration relative to baseline in CSF (%)
Secondary Endpoints and Results
Secondary endpoints
Developmental age (DA) determined by the Kyoto Scale of Psychological Development 2001 (KSPD) in the following three areas: postural-motor, cognitive-adaptive and language-social (an individualized face-to-face test).
Results
Monthly ICV administration of idursulfase-β maintained or increased DA in five of six patients compared with the historical control group receiving intravenous idursulfase.
At 100 weeks (about 2 years) after starting this study, six patients who received ICV idursulfase-β had a 5.1-month increase in mean DA compared with 13 historical control patients who received only intravenous administration of idursulfase.
Comparison with the historical control data in patients with MPS II
Change from screening period up to week 100 in DA (all 3 areas) by KSPD (months)
Change difference from screening period up to week 100 in DA (all 3 areas) by KSPD (months)