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

• ClinicalTrials.gov Identifier: NCT05422482
• Recruitment Status: Recruiting
• First Posted: June 16, 2022
• Last Update Posted: April 12, 2024
• Sponsor: GC Biopharma Corp
• Information provided by (Responsible Party): GC Biopharma Corp

Tracking Information

• First Submitted Date: May 31, 2022
• First Posted Date: June 16, 2022
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: September 20, 2022
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 11, 2024)

• Incidence and frequency of serious adverse events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

Original Primary Outcome Measures (submitted: June 13, 2022)

• Incidence and frequency of serious adverse events (SAEs) [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123) for each group
• Frequency and characteristics (severity, outcome, etc.) of adverse events [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123) for each group
• Presence of clinically significant abnormal echocardiography results [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123) for each group

Current Secondary Outcome Measures (submitted: April 11, 2024)

• Pharmacokinetic (PK) parameters - Cmax [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - Tmax [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - AUClast [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - AUCinf [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - t1/2 [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - CL/F (or CL) [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - Vd/F (or Vd) [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - Bioavailability (F) [ Time Frame: Week 2 to Week 22 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF [ Time Frame: Every 28 days from Week 1 through study completion (about 110 weeks) ]
  Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
• Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum [ Time Frame: 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) [ Time Frame: Every 28 days from Week 1 through study completion (about 110 weeks) ]
  Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
• Presence of anti-drug antibodies (ADAs) [ Time Frame: 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)

Original Secondary Outcome Measures (submitted: June 13, 2022)

• Pharmacokinetic (PK) parameters - Cmax [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - Tmax [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - AUClast [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - AUCinf [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - t1/2 [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - CL/F (or CL) [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - Vd/F (or Vd) [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacokinetic (PK) parameters - Bioavailability (F) [ Time Frame: Week 2 to Week 22 and Week 30 ]
  Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
• Pharmacodynamic (PD) parameters - HS in CSF [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
• Pharmacodynamic (PD) parameters - HS in serum [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
• Pharmacodynamic (PD) parameters - Urine GAG [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
• Presence of anti-drug antibodies (ADAs) [ Time Frame: Week 1 through study completion, an average of 6 months ]
  Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)

Current Other Pre-specified Outcome Measures (submitted: April 11, 2024)

• Development Function assessed by Bayley Scales of Infant and Toddler Development-III and/or Kaufman Assessment Battery for Children-II (BSID-III/KABC-II) [ Time Frame: Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110) ]
  All children will be tested for BSID-III, and children over the age of 3 will be also tested for KABC-II.
• Adaptive Function assessed by Vineland Adaptive Behavior Scales 2nd Ed. (VABS-II) [ Time Frame: Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110) ]
  Children under the age of 19 years will be tested for VABS-II.
• Quality of Life (Survey) assessed by Infant and Toddler Quality of Life Questionnaire (ITQOL) and/or Childhood Health Questionnaire parent form (CHQ-PF50) [ Time Frame: Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110) ]
  Children from the age of 2 months to 5 years will be tested for ITQOL, and children over the age of 5 will be tested for CHQ-PF50. The test performed during screening will be continued to be performed for each patient throughout the study period.
• Liver and Spleen volume [ Time Frame: Week 1 to phase I study completion (about 26 weeks) ]
  Liver and Spleen volume measured by MRI -phase I only

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety, Tolerability, PK and PD of Intracerebroventricular GC1123 in Patients With MPS Ⅱ
• Official Title: An Open-Label, Phase 1 and Extension Study to Evaluate the Safety, Tolerability, PK and PD of Intracerebroventricular GC1123 in Patients With MPS Ⅱ Who Have Central Nervous System Involvement and Are Receiving Treatment With Intravenous Drug
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Mucopolysaccharidosis II
• Hunter Syndrome

Intervention

Biological: GC1123

ICV-administered Hunterase, Idursulfase-ß

Study Arms

Experimental: GC1123 30mg

30 mg of IP will be administered every 28 days for all enrolled patients

Intervention: Biological: GC1123

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 13, 2022): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Months to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: GC Biopharma Corp.; 82-(0)31-260-9562; hi.kim@gccorp.com

• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT05422482
• Other Study ID Numbers: GC1123_MPS2_P0101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: GC Biopharma Corp
• Original Responsible Party: Same as current
• Current Study Sponsor: GC Biopharma Corp
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: GC Biopharma Corp
• Verification Date: April 2024