Intracerebral Hemorrhage
Conditions
Keywords
Ir-CPI, ICH, Secondary brain injury, Ixodes ricinus-Contact Phase Inhibitor, Neutrophil, Antithrombotic, Intracranial hemorrhage, Stroke, Brain, Inflammation, Neuroinflammation, Cerebrovascular disorders
Brief summary
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.
Interventions
DRUGIr-CPI
Participants receive a single intravenous dose of Ir-CPI during 48 hours
Sponsors
Bioxodes S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 5. * Modified Rankin Scale (mRS) score 0-2 prior to ICH symptom onset.
Exclusion criteria
* 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events | 360 days post-randomization | — |
| Incidence of abnormalities in physical examination | 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 | 7 days post-randomization | Measured by standard 12-lead ECG |
| Change from baseline in PR interval | 7 days post-randomization | Measured by standard 12-lead ECG |
| Change from baseline in QRS duration | 7 days post-randomization | Measured by standard 12-lead ECG |
| Change from baseline in QRS axis | 7 days post-randomization | Measured by standard 12-lead ECG |
| Change from baseline in QT interval | 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 | 7 days post-randomization | Blood pressure (systolic and diastolic) is measured using an automatic device |
| Change from baseline in heart rate | 7 days post-randomization | Heart rate is measured using an automatic device |
| Change from baseline in body temperature | 7 days post-randomization | Measurement of tympanic temperature |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in perihematomal oedema (PHO) and haemorrhage volumes | 10 days post-randomization | CT scans will be acquired by volumetric CT acquisition with reconstructions in 3 planes, in order to assess hematoma volume and perihematomal volume. Assessment of hematoma expansion will be performed by comparing follow-up CT scans with baseline CT. |
| Measurement of the effect of Ir-CPI on the activated Partial Thromboplastin Time (aPTT) | 7 days post-randomization | Activated partial thromboplastin time (aPTT) will be used as a pharmacodynamic marker |
| Measurement of the effect of Ir-CPI on the inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities | 7 days post-randomization | The inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities will be assessed to support the aPTT dynamics |
| Change from baseline in Ir-CPI plasma concentrations | 7 days post-randomization | — |
Countries
Belgium
Outcome results
None listed