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

• Sponsor: GC Biopharma Corp (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05422482
• Collaborator: (none)
• Enrollment: 12
• Locations: 3
• Arms: 3
• Anticipated Duration (Months): 33
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

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, ascending dose phase I 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 doses are 30 mg and 45 mg. After the 2nd dose on the 6th (last) patient in Group 1, Data and Safety Monitoring Boards (DSMB) will evaluate the safety and tolerability data of GC1123 to determine dose escalation if dose limiting toxicity (DLT) occurs in less than 2 out of 6 patients.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Sequential dose escalation modelSequential dose escalation model
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Open-Label, Ascending Dose 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
• Anticipated Study Start Date: Jun 1, 2022
• Anticipated Primary Completion Date: Mar 1, 2025
• Anticipated Study Completion Date: Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GC1123 30mg 30 mg of IP will be administered every 28 days for 6 patients enrolled in Group 1	Biological: GC1123; ICV-administered Hunterase, Idursulfase-ß
Experimental: GC1123 30mg + GC1123 45mg 30 mg of IP will be administered twice every 28 days for 2 patients enrolled in Group 2 45 mg of IP will be administered twice, and any DLT occurrence will be followed-up until 4 weeks after the 2nd 45 mg dose on the 2nd patient. DSMB will determine whether to proceed the administration after reviewing safety and tolerability data from 1) and 2). Group 2 will continue to receive 45 mg of IP administration	Biological: GC1123; ICV-administered Hunterase, Idursulfase-ß
Experimental: GC1123 45mg 45 mg of IP will be administered every 28 days for 4 patients enrolled in Group 3	Biological: GC1123; ICV-administered Hunterase, Idursulfase-ß

Outcome Measures

Primary Outcome Measures

1. Incidence and frequency of serious adverse events (SAEs) [Every 28 days from Week 1 through study completion (average of 6 months)]

   Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123) for each group

2. Frequency and characteristics (severity, outcome, etc.) of adverse events [Every 28 days from Week 1 through study completion (average of 6 months)]

   Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123) for each group

3. Presence of clinically significant abnormal echocardiography results [Week 1 to study completion, an average of 6 months]

   Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123) for each group

Secondary Outcome Measures

1. Pharmacokinetic (PK) parameters - Cmax [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

2. Pharmacokinetic (PK) parameters - Tmax [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

3. Pharmacokinetic (PK) parameters - AUClast [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

4. Pharmacokinetic (PK) parameters - AUCinf [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

5. Pharmacokinetic (PK) parameters - t1/2 [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

6. Pharmacokinetic (PK) parameters - CL/F (or CL) [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

7. Pharmacokinetic (PK) parameters - Vd/F (or Vd) [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

8. Pharmacokinetic (PK) parameters - Bioavailability (F) [Week 2 to Week 22 and Week 30]

   Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

9. Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF [Every 28 days from Week 1 through study completion (average of 6 months)]

   Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)

10. Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum [Every 28 days from Week 1 through study completion (average of 6 months)]

    Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)

11. Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG) [Every 28 days from Week 1 through study completion (average of 6 months)]

    Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)

12. Presence of anti-drug antibodies (ADAs) [Week 1 to Week 14, Week 26 (Group2 only), study completion (average of 6 months)]

    Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)

Other Outcome Measures

1. Development Quotient (DQ) assessed by Bayley Scales of Infant and Toddler Development-III/Kaufman Assessment Battery for Children-II (BSID-III/KABC-II) [Week 1 to study completion, an average of 6 months]

   Children under the age of 42 months will be tested for BSID-III, and children over the age of 3 will be tested for KABC-II. BSID-III test will be the dominant test to perform if the age lies in the range of 36 months to 42 months.

2. Adaptive Function assessed by Vineland Adaptive Behavior Scales 2nd Ed. (VABS-II) [Week 1 to study completion, an average of 6 months]

   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)/Childhood Health Questionnaire parent form (CHQ-PF50) [Week 1 to study completion, an average of 6 months]

   Children from the age of 2 monthst to 5 years will be tested for ITQoL, and children over the age of 5 will be tested for CHQ-PF50. ITQoL test will be the dominant test to perform if the child is 5 years old.

4. Liver and Spleen volume [Week 1 to study completion, an average of 6 months]

   Liver and Spleen volume measured by MRI

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Months to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 6 month 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 had experienced hypersensitivity or anaphylaxis to ingredients of the investigational product

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

Locations

	Site	City	State	Country	Postal Code
1	Pusan National University Yangsan Hospital	Pusan		Korea, Republic of	50612
2	Seoul National University	Seoul		Korea, Republic of	03080
3	Samsung Medical Center	Seoul		Korea, Republic of	06351

Sponsors and Collaborators

• GC Biopharma Corp

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GC Biopharma Corp
• ClinicalTrials.gov Identifier: NCT05422482
• Other Study ID Numbers: GC1123_MPS2_P0101
• First Posted: Jun 16, 2022
• Last Update Posted: Jun 22, 2022
• Last Verified: Jun 1, 2022

• 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

Study Results

No Results Posted as of Jun 22, 2022