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

Primary Purpose

Mucopolysaccharidosis II, Hunter Syndrome

Status
Recruiting
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
GC1123
Sponsored by
GC Biopharma Corp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis II

Eligibility Criteria

18 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pusan National University Yangsan HospitalRecruiting
  • Seoul National UniversityRecruiting
  • Samsung Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

GC1123 30mg

GC1123 30mg + GC1123 45mg

GC1123 45mg

Arm Description

30 mg of IP will be administered every 28 days for 6 patients enrolled in Group 1

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

45 mg of IP will be administered every 28 days for 4 patients enrolled in Group 3

Outcomes

Primary Outcome Measures

Incidence and frequency of serious adverse events (SAEs)
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
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
Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123) for each group

Secondary Outcome Measures

Pharmacokinetic (PK) parameters - Cmax
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - Tmax
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - AUClast
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - AUCinf
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - t1/2
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - CL/F (or CL)
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - Vd/F (or Vd)
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacokinetic (PK) parameters - Bioavailability (F)
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Presence of anti-drug antibodies (ADAs)
Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)

Full Information

First Posted
May 31, 2022
Last Updated
October 14, 2022
Sponsor
GC Biopharma Corp
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1. Study Identification

Unique Protocol Identification Number
NCT05422482
Brief Title
A Study to Evaluate the Safety, Tolerability, PK and PD of Intracerebroventricular GC1123 in Patients With MPS Ⅱ
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 20, 2022 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GC Biopharma Corp

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis II, Hunter Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Sequential dose escalation model
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GC1123 30mg
Arm Type
Experimental
Arm Description
30 mg of IP will be administered every 28 days for 6 patients enrolled in Group 1
Arm Title
GC1123 30mg + GC1123 45mg
Arm Type
Experimental
Arm Description
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
Arm Title
GC1123 45mg
Arm Type
Experimental
Arm Description
45 mg of IP will be administered every 28 days for 4 patients enrolled in Group 3
Intervention Type
Biological
Intervention Name(s)
GC1123
Intervention Description
ICV-administered Hunterase, Idursulfase-ß
Primary Outcome Measure Information:
Title
Incidence and frequency of serious adverse events (SAEs)
Description
Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123) for each group
Time Frame
Every 28 days from Week 1 through study completion (average of 6 months)
Title
Frequency and characteristics (severity, outcome, etc.) of adverse events
Description
Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123) for each group
Time Frame
Every 28 days from Week 1 through study completion (average of 6 months)
Title
Presence of clinically significant abnormal echocardiography results
Description
Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123) for each group
Time Frame
Week 1 to study completion, an average of 6 months
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) parameters - Cmax
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - Tmax
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - AUClast
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - AUCinf
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - t1/2
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - CL/F (or CL)
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - Vd/F (or Vd)
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacokinetic (PK) parameters - Bioavailability (F)
Description
Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF
Time Frame
Week 2 to Week 22 and Week 30
Title
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF
Description
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Time Frame
Every 28 days from Week 1 through study completion (average of 6 months)
Title
Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum
Description
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Time Frame
Every 28 days from Week 1 through study completion (average of 6 months)
Title
Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)
Description
Pharmacodynamic (PD) parameters of ICV-Hunterase (GC1123)
Time Frame
Every 28 days from Week 1 through study completion (average of 6 months)
Title
Presence of anti-drug antibodies (ADAs)
Description
Presence of anti-drug antibodies (ADAs) in CSF and serum, and neutralizing antibodies of ICV-Hunterase (GC1123)
Time Frame
Week 1 to Week 14, Week 26 (Group2 only), study completion (average of 6 months)
Other Pre-specified Outcome Measures:
Title
Development Quotient (DQ) assessed by Bayley Scales of Infant and Toddler Development-III/Kaufman Assessment Battery for Children-II (BSID-III/KABC-II)
Description
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.
Time Frame
Week 1 to study completion, an average of 6 months
Title
Adaptive Function assessed by Vineland Adaptive Behavior Scales 2nd Ed. (VABS-II)
Description
Children under the age of 19 years will be tested for VABS-II.
Time Frame
Week 1 to study completion, an average of 6 months
Title
Quality of Life (Survey) assessed by Infant and Toddler Quality of Life Questionnaire (ITQoL)/Childhood Health Questionnaire parent form (CHQ-PF50)
Description
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.
Time Frame
Week 1 to study completion, an average of 6 months
Title
Liver and Spleen volume
Description
Liver and Spleen volume measured by MRI
Time Frame
Week 1 to study completion, an average of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient who has been diagnosed with severe MPS Ⅱ (Hunter syndrome) Patient, aged 1.5 years (18 months) to 18 years at the time of the screening 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. Patient who is capable of undergoing neurosurgery, which has been confirmed by neurosurgeons and anesthesiologist. Patient eligible to execute patient evaluation activities during the clinical trial period, as assessed by the investigator Patient whose parents or legal representative are willing to participate in this clinical trial and provide written informed consent form Exclusion Criteria: Patient who has been administered with intrathecal Idursulfase in the past Patient with a history of bone marrow transplantation or cord blood transplant Patient with a history of ventriculoperitoneal shunt or other intracranial surgeries Patient with end-stage multiple organ dysfunction syndrome or other severe diseases Patient who is exposed to malignant neoplasm Patient who has received treatment with any investigational drug or device within 30 days prior to study entry Patient who had experienced hypersensitivity or anaphylaxis to ingredients of the investigational product Patient with a history of bronchotomy/tracheostomy, or patient with acute respiratory disease at the time of screening Patient who is ineligible to participate in the clinical trial due to laboratory test results or other reasons, as determined by the investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
GC Biopharma Corp.
Phone
82-(0)31-260-9039
Email
ceg@gccorp.com
Facility Information:
Facility Name
Pusan National University Yangsan Hospital
City
Pusan
ZIP/Postal Code
50612
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chong Kun Cheon, M.D.
Facility Name
Seoul National University
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ko Jung Min, M.D.
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong-Kyu Jin, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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