NCT00920647

A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase®

A Phase I/II, Randomized, Safety and Ascending Dose Ranging Study of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase in Pediatric Patients With Hunter Syndrome and Cognitive Impairment

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Shire · Industry
• Sex: Male
• Age: 3 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

Elaprase (idursulfase), a large molecular protein, is not expected to cross the blood brain barrier at therapeutic levels when administered intravenously. A new formulation of idursulfase, idursulfase-IT, that differs from that of the intravenous (IV) formulation, Elaprase, has been developed to be suitable for delivery into the cerebrospinal fluid (CSF) via intrathecal administration. This Phase I/II study is designed to obtain necessary safety and exposure data, as well as secondary and exploratory outcome measures, to be interpreted and used in the design of subsequent clinical trials.

Conditions

• Hunter Syndrome

Interventions

Type	Name	Description
OTHER	Control	3 dose cohorts were planned. Within each dose cohort, patients will be randomized to 1 of 2 treatment options: treatment with study drug or no treatment with 4 treated patients per dose group and a total of 4 untreated patients (1-2 untreated patients will be assigned in each dose cohort). They will not undergo surgical placement of an Intrathecal Drug Delivery Device (IDDD), and will not receive Idursulfase-IT.
DRUG	Idursulfase IT (1 mg)	The original design of the study was to test the dose levels of 10, 30 and 100 mg. This was based on a calculation of a minimally effective dose around 10 mg, with subsequent dose levels being chosen as increasing half-log steps. During the conduct of the study; however, it became clear that the 10 mg dose elicited a strong Pharmacodynamic response, as measured by a dramatic and sustained drop in the CSF GAG levels. This indicated the need to explore a lower level as a minimally effective dose level, leading to the introduction of the 1 mg group. Enrollment of patients in this dose cohort will commence after the last patient has been enrolled in 30 mg dose cohort. 4 patients will be undergo surgical placement of an IDDD and receive 1 mg idursulfase-IT as an IT injection via an IDDD once per month (ie, every 28 days) for 6 month.
DRUG	Idursulfase IT (10 mg)	Patients will be enrolled in 10 mg dose cohort and 30 mg dose cohort in a sequential, escalating fashion. 4 patients will undergo surgical placement of an IDDD and receive 10 mg idursulfase-IT as an intrathecal (IT) injection via an IDDD once per month (ie, every 28 days) for 6 month.
DRUG	Idursulfase IT (30 mg)	Patients will be enrolled in 10 mg dose cohort and 30 mg dose cohort in a sequential, escalating fashion. 4 patients will undergo surgical placement of an IDDD and receive 30 mg idursulfase-IT as an IT injection via an IDDD once per month (ie, every 28 days) for 6 month.

Timeline

• Start date: 2009-11-18
• Primary completion: 2012-10-29
• Completion: 2012-10-29
• First posted: 2009-06-15
• Last updated: 2021-06-28
• Results posted: 2014-05-16

Locations

3 sites across 2 countries: United States, United Kingdom