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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Incidence and frequency of serious adverse events (SAEs)
研究概览
简要总结
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
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 12 weeks 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
排除标准
- •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 have experience of hypersensitivity or anaphylaxis to ingredients of the investigational product at the time of screening
- •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
研究组 & 干预措施
GC1123 30mg
30 mg of IP will be administered every 28 days for all enrolled patients
干预措施: GC1123 (Biological)
结局指标
主要结局
Incidence and frequency of serious adverse events (SAEs)
时间窗: Every 28 days from Week 1 through study completion (about 110 weeks)
Incidence and frequency of serious adverse events (SAEs) after administration of ICV-Hunterase (GC1123)
Frequency and characteristics (severity, outcome, etc.) of adverse events
时间窗: Every 28 days from Week 1 through study completion (about 110 weeks)
Frequency and characteristics (severity, outcome, etc.) of adverse events after administration of ICV-Hunterase (GC1123)
Presence of clinically significant abnormal echocardiography results
时间窗: Week 1 to Phase I study completion (about 26 weeks)
Presence of clinically significant abnormal echocardiography results after administration of ICV-Hunterase (GC1123); phase I only
次要结局
- Pharmacokinetic (PK) parameters - t1/2(Week 2 to Week 22)
- Pharmacokinetic (PK) parameters - CL/F (or CL)(Week 2 to Week 22)
- Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in CSF(Every 28 days from Week 1 through study completion (about 110 weeks))
- Pharmacokinetic (PK) parameters - Tmax(Week 2 to Week 22)
- Pharmacokinetic (PK) parameters - Vd/F (or Vd)(Week 2 to Week 22)
- Pharmacodynamic (PD) parameters - Heparan Sulfate (HS) in serum(Every 28 days from Week 1 through study completion (about 110 weeks))
- Pharmacodynamic (PD) parameters - Urine Glycosaminoglycan (GAG)(Every 28 days from Week 1 through study completion (about 110 weeks))
- Pharmacokinetic (PK) parameters - Cmax(Week 2 to Week 22)
- Pharmacokinetic (PK) parameters - AUClast(Week 2 to Week 22)
- Pharmacokinetic (PK) parameters - AUCinf(Week 2 to Week 22)
- Pharmacokinetic (PK) parameters - Bioavailability (F)(Week 2 to Week 22)
- Presence of anti-drug antibodies (ADAs)(Approximately every 6 months (Week 2 [baseline], Week 18, Week 26, Week 54, Week 82, Week 110))