A Study to Evaluate the Safety, Tolerability, PK and PD of Intracerebroventricular GC1123 in Patients with MPS Ⅱ

Phase 1

Active, not recruiting

• Conditions: Hunter Syndrome; Mucopolysaccharidosis II
• Interventions: Biological: GC1123

• Registration Number: NCT05422482
• Lead Sponsor: GC Biopharma Corp

Brief Summary

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

Detailed Description

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 Timeline

• Study First Submitted: 2022-05-31
• Study First Submitted QC: 2022-06-13
• Study First Posted: 2022-06-16
• Study Start: 2022-09-20
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-13
• Last Update Posted: 2024-10-15
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Patient who has been diagnosed with severe MPS Ⅱ (Hunter syndrome)
2. Patient, aged 1.5 years (18 months) to 18 years at the time of the screening
3. Patient who has received and tolerated a minimum of 12 weeks of treatment with weekly intravenous treatment, and who has received 80% of the total planned infusions within that time frame.
4. Patient who is capable of undergoing neurosurgery, which has been confirmed by neurosurgeons and anesthesiologist.
5. Patient eligible to execute patient evaluation activities during the clinical trial period, as assessed by the investigator
6. Patient whose parents or legal representative are willing to participate in this clinical trial and provide written informed consent form

Exclusion Criteria

1. Patient who has been administered with intrathecal Idursulfase in the past
2. Patient with a history of bone marrow transplantation or cord blood transplant
3. Patient with a history of ventriculoperitoneal shunt or other intracranial surgeries
4. Patient with end-stage multiple organ dysfunction syndrome or other severe diseases
5. Patient who is exposed to malignant neoplasm
6. Patient who has received treatment with any investigational drug or device within 30 days prior to study entry
7. Patient who have experience of hypersensitivity or anaphylaxis to ingredients of the investigational product at the time of screening
8. Patient with a history of bronchotomy/tracheostomy, or patient with acute respiratory disease at the time of screening
9. Patient who is ineligible to participate in the clinical trial due to laboratory test results or other reasons, as determined by the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GC1123 30mg	GC1123	30 mg of IP will be administered every 28 days for all enrolled patients

Primary Outcome Measures

Name	Time	Method
Incidence and frequency of serious adverse events (SAEs)	Every 28 days from Week 1 through study completion (about 110 weeks)	Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123)
Frequency and characteristics (severity, outcome, etc.) of adverse events	Every 28 days from Week 1 through study completion (about 110 weeks)	Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123)
Presence of clinically significant abnormal echocardiography results	Week 1 to Phase I study completion (about 26 weeks)	Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123); phase I only

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) parameters - t1/2	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - CL/F (or CL)	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF	Every 28 days from Week 1 through study completion (about 110 weeks)	Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Pharmacokinetic (PK) parameters - Tmax	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - Vd/F (or Vd)	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum	Every 28 days from Week 1 through study completion (about 110 weeks)	Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)	Every 28 days from Week 1 through study completion (about 110 weeks)	Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Pharmacokinetic (PK) parameters - Cmax	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - AUClast	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - AUCinf	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - Bioavailability (F)	Week 2 to Week 22	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Presence of anti-drug antibodies (ADAs)	Approximately every 6 months (Week 2 [baseline], Week 18, Week 26, Week 54, Week 82, Week 110)	Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)

Trial Locations

Locations (3)

Pusan National University Yangsan Hospital; 🇰🇷 Pusan, Korea, Republic of

Seoul National University; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of