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

Mucopolysaccharidosis II Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05422482
• Other study ID #: GC1123_MPS2_P0101
• Status: Recruiting
• Phase: Phase 1
• Start date: September 20, 2022
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: GC Biopharma Corp
• Contact: GC Biopharma Corp.
• Phone: 82-(0)31-260-9562
• Email: hi.kim[@]gccorp.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 18 Years

Eligibility

Inclusion Criteria:

1. Patient who has been diagnosed with severe MPS ? (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

Related Conditions & MeSH terms

• Hunter Syndrome
• Mucopolysaccharidoses
• Mucopolysaccharidosis II

Intervention

Biological:
• GC1123
ICV-administered Hunterase, Idursulfase-ß

Locations

Country	Name	City	State
Korea, Republic of	Pusan National University Yangsan Hospital	Pusan
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
GC Biopharma Corp

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Development Function assessed by Bayley Scales of Infant and Toddler Development-III and/or Kaufman Assessment Battery for Children-II (BSID-III/KABC-II)	All children will be tested for BSID-III, and children over the age of 3 will be also tested for KABC-II.	Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110)
Other	Adaptive Function assessed by Vineland Adaptive Behavior Scales 2nd Ed. (VABS-II)	Children under the age of 19 years will be tested for VABS-II.	Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110)
Other	Quality of Life (Survey) assessed by Infant and Toddler Quality of Life Questionnaire (ITQOL) and/or Childhood Health Questionnaire parent form (CHQ-PF50)	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.	Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110)
Other	Liver and Spleen volume	Liver and Spleen volume measured by MRI -phase I only	Week 1 to phase I study completion (about 26 weeks)
Primary	Incidence and frequency of serious adverse events (SAEs)	Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123)	Every 28 days from Week 1 through study completion (about 110 weeks)
Primary	Frequency and characteristics (severity, outcome, etc.) of adverse events	Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123)	Every 28 days from Week 1 through study completion (about 110 weeks)
Primary	Presence of clinically significant abnormal echocardiography results	Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123); phase I only	Week 1 to Phase I study completion (about 26 weeks)
Secondary	Pharmacokinetic (PK) parameters - Cmax	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - Tmax	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - AUClast	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - AUCinf	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - t1/2	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - CL/F (or CL)	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - Vd/F (or Vd)	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacokinetic (PK) parameters - Bioavailability (F)	Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF	Week 2 to Week 22
Secondary	Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF	Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)	Every 28 days from Week 1 through study completion (about 110 weeks)
Secondary	Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum	Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)	Every 28 days from Week 1 through study completion (about 110 weeks)
Secondary	Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)	Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)	Every 28 days from Week 1 through study completion (about 110 weeks)
Secondary	Presence of anti-drug antibodies (ADAs)	Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)	Approximately every 6 months (Week 2 [baseline], Week 18, Week 26, Week 54, Week 82, Week 110)