A Phase IIa, Randomized, Open-label, Proof-of-Concept Study to Evaluate Safety, Tolerability and Efficacy of Ir-CPI in Patients With Spontaneous Intracerebral Haemorrhage
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 12
- 主要终点
- Number of Participants with Adverse Events
研究概览
简要总结
The purpose of the study is to provide a first assessment of safety, tolerability and efficacy of Ir-CPI, administered on top of standard-of-care, on secondary brain injury in patients with spontaneous intracerebral haemorrhage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients aged ≥ 18 years.
- •Written informed consent obtained before any study assessment. If the patient is not able to give the informed consent personally, consent by a legal representative as defined by local law and regulation is acceptable.
- •First-ever, spontaneous, supratentorial intracerebral haemorrhage in cerebral cortex or deep brain structures (putamen, thalamus, caudate, and associated deep white matter tracts) with a volume ≥ 5 mL and ≤ 60 mL determined by non-contrast CT scan.
- •Patients with Glasgow Coma Scale (GCS) best motor score no less than
- •Modified Rankin Scale (mRS) score 0-2 prior to ICH symptom onset.
排除标准
- •History of personal or familial bleeding disorders; including prolonged or unusual bleeding.
- •Known deficiency in factor XII (FXII) or haemophilia type A (FVII) or type B (FIX) or type C (FXI).
- •Infratentorial (midbrain, pons, medulla, or cerebellum) ICH.
- •Secondary ICH due to aneurysm, brain tumour, arteriovenous malformation, thrombocytopenia, coagulopathy, acute sepsis, traumatic brain injury (TBI), or disseminated intravascular coagulation (DIC).
- •Planned neurosurgical hematoma evacuation or other urgent surgical intervention (i.e., surgical relief of increased intracranial pressure) on initial presentation.
- •Anticoagulation reversal treatment.
- •Patients with intraventricular haemorrhage (IVH) having a Graeb score of >3 on initial presentation. Patients must not have blood in the 4th ventricle and may only have blood in the 3rd ventricle in the absence of ventricular expansion. Trace or mild haemorrhage in either or both lateral ventricles is permitted. Patients with hydrocephalus determined radiologically on initial presentation are excluded regardless of Graeb score.
- •Use of immunosuppressive or immune-modulating therapy at admission (e.g., steroids, methotrexate, monoclonal antibodies, etc).
- •Patients with active systemic bacterial, viral or fungal infections.
- •Women of childbearing potential.
- •Have a body weight > 120 kg at screening.
- •Severe renal impairment (eGFR < 30 mL/min/1.73 m2).
研究组 & 干预措施
Standard care
Only standard of care
Ir-CPI
Ir-CPI will be administered on top of standard of care
干预措施: Ir-CPI (Drug)
结局指标
主要结局
Number of Participants with Adverse Events
时间窗: 360 days post-randomization
Incidence of abnormalities in physical examination
时间窗: 7 days post-randomization
A complete physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal, dermatological, neurological (including basic neurological testing for isocoria, light reflexes, gait and balance), musculoskeletal and lymphatic systems, in addition to head, eyes, ears, nose, throat, and neck.
Change from baseline in HR interval
时间窗: 7 days post-randomization
Measured by standard 12-lead ECG
Change from baseline in PR interval
时间窗: 7 days post-randomization
Measured by standard 12-lead ECG
Change from baseline in QRS duration
时间窗: 7 days post-randomization
Measured by standard 12-lead ECG
Change from baseline in QRS axis
时间窗: 7 days post-randomization
Measured by standard 12-lead ECG
Change from baseline in QT interval
时间窗: 7 days post-randomization
Measured by standard 12-lead ECG. Two corrections of the QT interval will be investigated: Fridericia's correction (QTcF) and Bazett's correction (QTcB)
Change from baseline in blood pressure
时间窗: 7 days post-randomization
Blood pressure (systolic and diastolic) is measured using an automatic device
Change from baseline in heart rate
时间窗: 7 days post-randomization
Heart rate is measured using an automatic device
Change from baseline in body temperature
时间窗: 7 days post-randomization
Measurement of tympanic temperature
次要结局
- Change from baseline in perihematomal oedema (PHO) and haemorrhage volumes(10 days post-randomization)
- Measurement of the effect of Ir-CPI on the activated Partial Thromboplastin Time (aPTT)(7 days post-randomization)
- Measurement of the effect of Ir-CPI on the inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities(7 days post-randomization)
- Change from baseline in Ir-CPI plasma concentrations(7 days post-randomization)