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Trial record 1 of 1 for:    NCT05422482
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A Study to Evaluate the Safety, Tolerability, PK and PD of Intracerebroventricular GC1123 in Patients With MPS Ⅱ

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ClinicalTrials.gov Identifier: NCT05422482
Recruitment Status : Recruiting
First Posted : June 16, 2022
Last Update Posted : October 17, 2022
Sponsor:
Information provided by (Responsible Party):
GC Biopharma Corp

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Sequential 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
Actual Study Start Date : September 20, 2022
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : March 2025


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
  1. 30 mg of IP will be administered twice every 28 days for 2 patients enrolled in Group 2
  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.
  3. DSMB will determine whether to proceed the administration after reviewing safety and tolerability data from 1) and 2).
  4. 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




Primary Outcome Measures :
  1. Incidence and frequency of serious adverse events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 2 to Week 22 and Week 30 ]
    Pharmacokinetic (PK) parameters of ICV-Hunterase (GC1123) in serum and CSF

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Week 1 to study completion, an average of 6 months ]
    Liver and Spleen volume measured by MRI



Information from the National Library of Medicine

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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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05422482


Contacts
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Contact: GC Biopharma Corp. 82-(0)31-260-9039 ceg@gccorp.com

Locations
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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
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Responsible Party: GC Biopharma Corp
ClinicalTrials.gov Identifier: NCT05422482    
Other Study ID Numbers: GC1123_MPS2_P0101
First Posted: June 16, 2022    Key Record Dates
Last Update Posted: October 17, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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