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

Intracerebral Hemorrhage Clinical Trial

— BIRCH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05970224
• Other study ID #: Clin_IrCPI_201
• Secondary ID: 2022-500491-53-0
• Status: Recruiting
• Phase: Phase 2
• Start date: November 17, 2023
• Est. completion date: July 2027

Study information

• Verified date: May 2024
• Source: Bioxodes S.A.
• Contact: Charlotte Corbisier
• Phone: +32 (0)472 21 01 20
• Email: charlotte.corbisier[@]bioxodes.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: July 2027
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage

Intervention

Drug:
• Ir-CPI
Participants receive a single intravenous dose of Ir-CPI during 48 hours

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan	Brugge	West Flanders
Belgium	HUB Erasme	Brussels
Belgium	UCL St Luc	Brussels
Belgium	UZ Brussel	Brussels
Belgium	UZ Gent	Gent	East Flanders
Belgium	AZ Groeninge	Kortrijk	West Flanders
Belgium	UZ Leuven	Leuven	Flemish Brabant
Belgium	Clinique CHC MontLégia	Liège
Belgium	CHU Ambroise Paré	Mons	Hainaut
Belgium	AZ Damiaan	Oostende	West Flanders

Sponsors (1)

Lead Sponsor	Collaborator
Bioxodes S.A.

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events		360 days post-randomization
Primary	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
Primary	Change from baseline in HR interval	Measured by standard 12-lead ECG	7 days post-randomization
Primary	Change from baseline in PR interval	Measured by standard 12-lead ECG	7 days post-randomization
Primary	Change from baseline in QRS duration	Measured by standard 12-lead ECG	7 days post-randomization
Primary	Change from baseline in QRS axis	Measured by standard 12-lead ECG	7 days post-randomization
Primary	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
Primary	Change from baseline in blood pressure	Blood pressure (systolic and diastolic) is measured using an automatic device	7 days post-randomization
Primary	Change from baseline in heart rate	Heart rate is measured using an automatic device	7 days post-randomization
Primary	Change from baseline in body temperature	Measurement of tympanic temperature	7 days post-randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in Ir-CPI plasma concentrations		7 days post-randomization