The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of intracerebroventricular GC1123 in patients with MPS Ⅱ who have central nervous system involvement and are receiving treatment with intravenous drug
This study is designed as prospective, open-label, phase I and extension study. Safety, tolerability, pharmacokinetic, and pharmacodynamic properties of repeat-dose treatment of ICV-administered investigational product will be studied in patients undergoing standard treatments. Patients will undergo cerebrospinal fluid (CSF) reservoir device implantation surgery on their scalps, and the reservoirs will be used to administer GC1123 to the cerebral ventricles monthly (every 28 days). The planned administering dose is 30 mg. After the 2nd dose on the 6th patient, Data and Safety Monitoring Boards (DSMB) will evaluate the safety and tolerability data of GC1123. The planned duration of the sutdy is total about 2 years (phase I and extension)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
ICV-administered Hunterase, Idursulfase-ß
Pusan National University Yangsan Hospital
Pusan, South Korea
Seoul National University
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Incidence and frequency of serious adverse events (SAEs)
Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123)
Time frame: Every 28 days from Week 1 through study completion (about 110 weeks)
Frequency and characteristics (severity, outcome, etc.) of adverse events
Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123)
Time frame: Every 28 days from Week 1 through study completion (about 110 weeks)
Presence of clinically significant abnormal echocardiography results
Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123); phase I only
Time frame: Week 1 to Phase I study completion (about 26 weeks)
Pharmacokinetic (PK) parameters - Cmax
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - Tmax
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - AUClast
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - AUCinf
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
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Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - t1/2
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - CL/F (or CL)
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - Vd/F (or Vd)
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacokinetic (PK) parameters - Bioavailability (F)
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time frame: Week 2 to Week 22
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Time frame: Every 28 days from Week 1 through study completion (about 110 weeks)
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Time frame: Every 28 days from Week 1 through study completion (about 110 weeks)
Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Time frame: Every 28 days from Week 1 through study completion (about 110 weeks)
Presence of anti-drug antibodies (ADAs)
Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)
Time frame: Approximately every 6 months (Week 2 [baseline], Week 18, Week 26, Week 54, Week 82, Week 110)