A Study to Evaluate the Safety, Tolerability and the Effects of Ixodes Ricinus-Contact Phase Inhibitor (Ir-CPI) in Adult Patients With Spontaneous Intracerebral Haemorrhage

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Intracerebral Hemorrhage

Intervention / Treatment
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* Drug: Ir-CPI


Participation Criteria
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Eligibility Criteria
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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. Planned 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ir-CPI<br>Ir-CPI will be administered on top of standard of care | Drug: Ir-CPI<br>* Participants receive a single intravenous dose of Ir-CPI during 48 hours<br>|
| No Intervention: Standard care<br>Only standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events |  | 360 days post-randomization | 
| Incidence of abnormalities in physical examination | 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. | 7 days post-randomization | 
| Change from baseline in HR interval | Measured by standard 12-lead ECG | 7 days post-randomization | 
| Change from baseline in PR interval | Measured by standard 12-lead ECG | 7 days post-randomization | 
| Change from baseline in QRS duration | Measured by standard 12-lead ECG | 7 days post-randomization | 
| Change from baseline in QRS axis | Measured by standard 12-lead ECG | 7 days post-randomization | 
| Change from baseline in QT interval | Measured by standard 12-lead ECG. Two corrections of the QT interval will be investigated: Fridericia's correction (QTcF) and Bazett's correction (QTcB) | 7 days post-randomization | 
| Change from baseline in blood pressure | Blood pressure (systolic and diastolic) is measured using an automatic device | 7 days post-randomization | 
| Change from baseline in heart rate | Heart rate is measured using an automatic device | 7 days post-randomization | 
| Change from baseline in body temperature | Measurement of tympanic temperature | 7 days post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in perihematomal oedema (PHO) and haemorrhage volumes | 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. | 10 days post-randomization | 
| Measurement of the effect of Ir-CPI on the activated Partial Thromboplastin Time (aPTT) | Activated partial thromboplastin time (aPTT) will be used as a pharmacodynamic marker | 7 days post-randomization | 
| Measurement of the effect of Ir-CPI on the inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities | The inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities will be assessed to support the aPTT dynamics | 7 days post-randomization | 
| Change from baseline in Ir-CPI plasma concentrations |  | 7 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Brain, Inflammation, Neuroinflammation, Ir-CPI, ICH, Secondary brain injury, Ixodes ricinus-Contact Phase Inhibitor, Neutrophil, Antithrombotic, Intracranial hemorrhage, Cerebrovascular disorders