Back to resultsA 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)
Primary Purpose
Intracerebral Hemorrhage
Status
Recruiting
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Ir-CPI
Sponsored by
About this trial
This is an interventional treatment trial for Intracerebral Hemorrhage focused on measuring Ir-CPI, ICH, Secondary brain injury, Ixodes ricinus-Contact Phase Inhibitor, Neutrophil, Antithrombotic, Intracranial hemorrhage, Stroke, Brain, Inflammation, Neuroinflammation, Cerebrovascular disorders
Eligibility Criteria
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).
Sites / Locations
- UZ GentRecruiting
- UZ LeuvenRecruiting
- CHU Ambroise ParéRecruiting
- AZ GroeningeRecruiting
- UCL St LucRecruiting
- UZ BrusselRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Ir-CPI
Standard care
Arm Description
Ir-CPI will be administered on top of standard of care
Only standard of care
Outcomes
Primary Outcome Measures
Number of Participants with Adverse Events
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.
Change from baseline in HR interval
Measured by standard 12-lead ECG
Change from baseline in PR interval
Measured by standard 12-lead ECG
Change from baseline in QRS duration
Measured by standard 12-lead ECG
Change from baseline in QRS axis
Measured by standard 12-lead ECG
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)
Change from baseline in blood pressure
Blood pressure (systolic and diastolic) is measured using an automatic device
Change from baseline in heart rate
Heart rate is measured using an automatic device
Change from baseline in body temperature
Measurement of tympanic temperature
Secondary Outcome Measures
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.
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
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
Change from baseline in Ir-CPI plasma concentrations
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05970224
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2023 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
July 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioxodes S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracerebral Hemorrhage
Keywords
Ir-CPI, ICH, Secondary brain injury, Ixodes ricinus-Contact Phase Inhibitor, Neutrophil, Antithrombotic, Intracranial hemorrhage, Stroke, Brain, Inflammation, Neuroinflammation, Cerebrovascular disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ir-CPI
Arm Type
Experimental
Arm Description
Ir-CPI will be administered on top of standard of care
Arm Title
Standard care
Arm Type
No Intervention
Arm Description
Only standard of care
Intervention Type
Drug
Intervention Name(s)
Ir-CPI
Intervention Description
Participants receive a single intravenous dose of Ir-CPI during 48 hours
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events
Time Frame
360 days post-randomization
Title
Incidence of abnormalities in physical examination
Description
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.
Time Frame
7 days post-randomization
Title
Change from baseline in HR interval
Description
Measured by standard 12-lead ECG
Time Frame
7 days post-randomization
Title
Change from baseline in PR interval
Description
Measured by standard 12-lead ECG
Time Frame
7 days post-randomization
Title
Change from baseline in QRS duration
Description
Measured by standard 12-lead ECG
Time Frame
7 days post-randomization
Title
Change from baseline in QRS axis
Description
Measured by standard 12-lead ECG
Time Frame
7 days post-randomization
Title
Change from baseline in QT interval
Description
Measured by standard 12-lead ECG. Two corrections of the QT interval will be investigated: Fridericia's correction (QTcF) and Bazett's correction (QTcB)
Time Frame
7 days post-randomization
Title
Change from baseline in blood pressure
Description
Blood pressure (systolic and diastolic) is measured using an automatic device
Time Frame
7 days post-randomization
Title
Change from baseline in heart rate
Description
Heart rate is measured using an automatic device
Time Frame
7 days post-randomization
Title
Change from baseline in body temperature
Description
Measurement of tympanic temperature
Time Frame
7 days post-randomization
Secondary Outcome Measure Information:
Title
Change from baseline in perihematomal oedema (PHO) and haemorrhage volumes
Description
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.
Time Frame
10 days post-randomization
Title
Measurement of the effect of Ir-CPI on the activated Partial Thromboplastin Time (aPTT)
Description
Activated partial thromboplastin time (aPTT) will be used as a pharmacodynamic marker
Time Frame
7 days post-randomization
Title
Measurement of the effect of Ir-CPI on the inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities
Description
The inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities will be assessed to support the aPTT dynamics
Time Frame
7 days post-randomization
Title
Change from baseline in Ir-CPI plasma concentrations
Time Frame
7 days post-randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Charlotte Corbisier
Phone
+32 (0)472 21 01 20
Email
charlotte.corbisier@bioxodes.com
Facility Information:
Facility Name
UZ Gent
City
Gent
State/Province
East Flanders
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wendy Stoop
Facility Name
UZ Leuven
City
Leuven
State/Province
Flemish Brabant
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annemie Devroye
Facility Name
CHU Ambroise Paré
City
Mons
State/Province
Hainaut
ZIP/Postal Code
7000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Virginie Vanderhaegen
Facility Name
AZ Groeninge
City
Kortrijk
State/Province
West Flanders
ZIP/Postal Code
8500
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isabelle Vanpantghem
Facility Name
UCL St Luc
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ayhan Findik
Facility Name
UZ Brussel
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Vandaele
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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
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