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

Study Description

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

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis II; Hunter Syndrome	Biological: GC1123	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 20, 2022
• Estimated Primary Completion Date: June 2026
• Estimated Study Completion Date: June 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: GC1123 30mg; 30 mg of IP will be administered every 28 days for all enrolled patients	Biological: GC1123; ICV-administered Hunterase, Idursulfase-ß

Outcome Measures

Primary Outcome Measures :

1. 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)
2. 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)
3. 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

Secondary Outcome Measures :

1. Pharmacokinetic (PK) parameters - Cmax [ Time Frame: Week 2 to Week 22 ]
   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
2. Pharmacokinetic (PK) parameters - Tmax [ Time Frame: Week 2 to Week 22 ]
   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
3. Pharmacokinetic (PK) parameters - AUClast [ Time Frame: Week 2 to Week 22 ]
   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
4. Pharmacokinetic (PK) parameters - AUCinf [ Time Frame: Week 2 to Week 22 ]
   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
5. Pharmacokinetic (PK) parameters - t1/2 [ Time Frame: Week 2 to Week 22 ]
   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
6. 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
7. 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
8. Pharmacokinetic (PK) parameters - Bioavailability (F) [ Time Frame: Week 2 to Week 22 ]
   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
9. 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)
10. 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)
11. 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)
12. 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)

Other Outcome Measures:

1. 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.
2. 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.
3. 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.
4. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Months to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

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

Locations

Korea, Republic of

Pusan National University Yangsan Hospital; Recruiting

Pusan, Korea, Republic of, 50612

Principal Investigator: Chong Kun Cheon, M.D.

Seoul National University; Recruiting

Seoul, Korea, Republic of, 03080

Principal Investigator: Ko Jung Min, M.D.

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 06351

Principal Investigator: Dong-Kyu Jin, M.D.

Sponsors and Collaborators

GC Biopharma Corp

More Information

• Responsible Party: GC Biopharma Corp
• ClinicalTrials.gov Identifier: NCT05422482
• Other Study ID Numbers: GC1123_MPS2_P0101
• First Posted: June 16, 2022
• Last Update Posted: April 12, 2024
• Last Verified: April 2024

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

Additional relevant MeSH terms:

Mucopolysaccharidosis II; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System