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 (BIRCH)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Ir-CPI

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Charlotte Corbisier; Phone Number: +32 (0)472 21 01 20; Email: charlotte.corbisier@bioxodes.com

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • UZ Brussel
    • Contact: Karen Vandaele
  • Brussels, Belgium
    • Recruiting
    • UCL St Luc
    • Contact: Ayhan Findik
  • Brussels, Belgium, 1070
    • Recruiting
    • HUB Erasme
    • Contact: Patrick Lamotte
  • East Flanders
    • Gent, East Flanders, Belgium, 9000
      • Recruiting
      • UZ Gent
      • Contact: Wendy Stoop
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium
      • Recruiting
      • UZ Leuven
      • Contact: Annemie Devroye
  • Hainaut
    • Mons, Hainaut, Belgium, 7000
      • Recruiting
      • CHU Ambroise Pare
      • Contact: Virginie Vanderhaegen
  • West Flanders
    • Brugge, West Flanders, Belgium, 8000
      • Recruiting
      • AZ Sint-Jan
      • Contact: Heleen Couckuyt
    • Kortrijk, West Flanders, Belgium, 8500
      • Recruiting
      • Az Groeninge
      • Contact: Isabelle Vanpantghem
    • Oostende, West Flanders, Belgium, 8400
      • Recruiting
      • AZ Damiaan
      • Contact: Louise Vandenbroucke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of Participants with Adverse Events		360 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

Collaborators and Investigators

• Sponsor: Bioxodes S.A.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Stroke; Neuroinflammation; ICH; Brain; Cerebrovascular disorders; Neutrophil; Intracranial hemorrhage; Antithrombotic; Ir-CPI; Secondary brain injury; Ixodes ricinus-Contact Phase Inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: Clin_IrCPI_201; 2022-500491-53-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No