Clinical trial NCT05422482: A Study to Evaluate the Safety, Tolerability, PK and PD of Intracerebroventricular GC1123 in Patients with MPS Ⅱ
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Mucopolysaccharidosis II
Hunter Syndrome
Lead sponsor: GC Biopharma Corp
Sponsor class: INDUSTRY
First posted: 2022-06-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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, 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)

Eligibility 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

Primary outcomes:
measure: Incidence and frequency of serious adverse events (SAEs)
timeFrame: Every 28 days from Week 1 through study completion (about 110 weeks)
measure: Frequency and characteristics (severity, outcome, etc.) of adverse events
timeFrame: Every 28 days from Week 1 through study completion (about 110 weeks)
measure: Presence of clinically significant abnormal echocardiography results
timeFrame: Week 1 to Phase I study completion (about 26 weeks)
Secondary outcomes:
measure: Pharmacokinetic (PK) parameters - Cmax
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - Tmax
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - AUClast
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - AUCinf
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - t1/2
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - CL/F (or CL)
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - Vd/F (or Vd)
timeFrame: Week 2 to Week 22
measure: Pharmacokinetic (PK) parameters - Bioavailability (F)
timeFrame: Week 2 to Week 22
measure: Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF
timeFrame: Every 28 days from Week 1 through study completion (about 110 weeks)
measure: Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum
timeFrame: Every 28 days from Week 1 through study completion (about 110 weeks)
measure: Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)
timeFrame: Every 28 days from Week 1 through study completion (about 110 weeks)
measure: Presence of anti-drug antibodies (ADAs)
timeFrame: Approximately every 6 months (Week 2 [baseline], Week 18, Week 26, Week 54, Week 82, Week 110)
Other outcomes:
measure: Development Function assessed by Bayley Scales of Infant and Toddler Development-III and/or Kaufman Assessment Battery for Children-II (BSID-III/KABC-II)
timeFrame: Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110)
measure: Adaptive Function assessed by Vineland Adaptive Behavior Scales 2nd Ed. (VABS-II)
timeFrame: Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110)
measure: Quality of Life (Survey) assessed by Infant and Toddler Quality of Life Questionnaire (ITQOL) and/or Childhood Health Questionnaire parent form (CHQ-PF50)
timeFrame: Approximately every 6 months (Week 1 [baseline], Week 26, Week 54, Week 82, Week 110)
measure: Liver and Spleen volume
timeFrame: Week 1 to phase I study completion (about 26 weeks)
Locations:
city: Pusan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: