xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05970224</url>
    </required_header>
    <id_info>
      <org_study_id>Clin_IrCPI_201</org_study_id>
      <secondary_id>2022-500491-53-00</secondary_id>
      <nct_id>NCT05970224</nct_id>
    </id_info>
    <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</brief_title>
    <acronym>BIRCH</acronym>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Bioxodes S.A.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Bioxodes S.A.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of the study is to provide a first assessment of safety, tolerability and&#xD;
        efficacy of Ir-CPI, administered on top of standard-of-care, on secondary brain injury in&#xD;
        patients with spontaneous intracerebral haemorrhage.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 27, 2023</start_date>
    <completion_date type="Anticipated">July 2027</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of Participants with Adverse Events</measure>
      <time_frame>360 days post-randomization</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of abnormalities in physical examination</measure>
      <time_frame>7 days post-randomization</time_frame>
      <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.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in HR interval</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Measured by standard 12-lead ECG</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in PR interval</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Measured by standard 12-lead ECG</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in QRS duration</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Measured by standard 12-lead ECG</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in QRS axis</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Measured by standard 12-lead ECG</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in QT interval</measure>
      <time_frame>7 days post-randomization</time_frame>
      <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)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in blood pressure</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Blood pressure (systolic and diastolic) is measured using an automatic device</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in heart rate</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Heart rate is measured using an automatic device</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in body temperature</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Measurement of tympanic temperature</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in perihematomal oedema (PHO) and haemorrhage volumes</measure>
      <time_frame>10 days post-randomization</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurement of the effect of Ir-CPI on the activated Partial Thromboplastin Time (aPTT)</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>Activated partial thromboplastin time (aPTT) will be used as a pharmacodynamic marker</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurement of the effect of Ir-CPI on the inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities</measure>
      <time_frame>7 days post-randomization</time_frame>
      <description>The inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities will be assessed to support the aPTT dynamics</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Ir-CPI plasma concentrations</measure>
      <time_frame>7 days post-randomization</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">32</enrollment>
    <condition>Intracerebral Hemorrhage</condition>
    <arm_group>
      <arm_group_label>Ir-CPI</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Ir-CPI will be administered on top of standard of care</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard care</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Only standard of care</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ir-CPI</intervention_name>
      <description>Participants receive a single intravenous dose of Ir-CPI during 48 hours</description>
      <arm_group_label>Ir-CPI</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or female patients aged ≥ 18 years.&#xD;
  &#xD;
            -  Written informed consent obtained before any study assessment. If the patient is not&#xD;
               able to give the informed consent personally, consent by a legal representative as&#xD;
               defined by local law and regulation is acceptable.&#xD;
  &#xD;
            -  First-ever, spontaneous, supratentorial intracerebral haemorrhage in cerebral cortex&#xD;
               or deep brain structures (putamen, thalamus, caudate, and associated deep white matter&#xD;
               tracts) with a volume ≥ 5 mL and ≤ 60 mL determined by non-contrast CT scan.&#xD;
  &#xD;
            -  Patients with Glasgow Coma Scale (GCS) best motor score no less than 5.&#xD;
  &#xD;
            -  Modified Rankin Scale (mRS) score 0-2 prior to ICH symptom onset.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of personal or familial bleeding disorders; including prolonged or unusual&#xD;
               bleeding.&#xD;
  &#xD;
            -  Known deficiency in factor XII (FXII) or haemophilia type A (FVII) or type B (FIX) or&#xD;
               type C (FXI).&#xD;
  &#xD;
            -  Infratentorial (midbrain, pons, medulla, or cerebellum) ICH.&#xD;
  &#xD;
            -  Secondary ICH due to aneurysm, brain tumour, arteriovenous malformation,&#xD;
               thrombocytopenia, coagulopathy, acute sepsis, traumatic brain injury (TBI), or&#xD;
               disseminated intravascular coagulation (DIC).&#xD;
  &#xD;
            -  Planned neurosurgical hematoma evacuation or other urgent surgical intervention (i.e.,&#xD;
               surgical relief of increased intracranial pressure) on initial presentation.&#xD;
  &#xD;
            -  Planned anticoagulation reversal treatment.&#xD;
  &#xD;
            -  Patients with intraventricular haemorrhage (IVH) having a Graeb score of &gt;3 on initial&#xD;
               presentation. Patients must not have blood in the 4th ventricle and may only have&#xD;
               blood in the 3rd ventricle in the absence of ventricular expansion. Trace or mild&#xD;
               haemorrhage in either or both lateral ventricles is permitted. Patients with&#xD;
               hydrocephalus determined radiologically on initial presentation are excluded&#xD;
               regardless of Graeb score.&#xD;
  &#xD;
            -  Use of immunosuppressive or immune-modulating therapy at admission (e.g., steroids,&#xD;
               methotrexate, monoclonal antibodies, etc).&#xD;
  &#xD;
            -  Patients with active systemic bacterial, viral or fungal infections.&#xD;
  &#xD;
            -  Women of childbearing potential.&#xD;
  &#xD;
            -  Have a body weight &gt; 120 kg at screening.&#xD;
  &#xD;
            -  Severe renal impairment (eGFR &lt; 30 mL/min/1.73 m2).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Charlotte Corbisier</last_name>
      <phone>+32 (0)472 21 01 20</phone>
      <email>charlotte.corbisier@bioxodes.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>UZ Gent</name>
        <address>
          <city>Gent</city>
          <state>East Flanders</state>
          <zip>9000</zip>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Wendy Stoop</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>UZ Leuven</name>
        <address>
          <city>Leuven</city>
          <state>Flemish Brabant</state>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Annemie Devroye</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>CHU Ambroise Paré</name>
        <address>
          <city>Mons</city>
          <state>Hainaut</state>
          <zip>7000</zip>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Virginie Vanderhaegen</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>AZ Groeninge</name>
        <address>
          <city>Kortrijk</city>
          <state>West Flanders</state>
          <zip>8500</zip>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Isabelle Vanpantghem</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>UCL St Luc</name>
        <address>
          <city>Brussels</city>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ayhan Findik</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>UZ Brussel</name>
        <address>
          <city>Brussels</city>
          <country>Belgium</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Karen Vandaele</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Belgium</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Ir-CPI</keyword>
    <keyword>ICH</keyword>
    <keyword>Secondary brain injury</keyword>
    <keyword>Ixodes ricinus-Contact Phase Inhibitor</keyword>
    <keyword>Neutrophil</keyword>
    <keyword>Antithrombotic</keyword>
    <keyword>Intracranial hemorrhage</keyword>
    <keyword>Stroke</keyword>
    <keyword>Brain</keyword>
    <keyword>Inflammation</keyword>
    <keyword>Neuroinflammation</keyword>
    <keyword>Cerebrovascular disorders</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cerebral Hemorrhage</mesh_term>
      <mesh_term>Hemorrhage</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05970224
  org study id: Clin_IrCPI_201
  secondary id: 2022-500491-53-00
  nct id: NCT05970224
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of Participants with Adverse Events
  time frame: 360 days post-randomization
  measure: Incidence of abnormalities in physical examination
  time frame: 7 days post-randomization
  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.
  measure: Change from baseline in HR interval
  time frame: 7 days post-randomization
  description: Measured by standard 12-lead ECG
  measure: Change from baseline in PR interval
  time frame: 7 days post-randomization
  description: Measured by standard 12-lead ECG
  measure: Change from baseline in QRS duration
  time frame: 7 days post-randomization
  description: Measured by standard 12-lead ECG
  measure: Change from baseline in QRS axis
  time frame: 7 days post-randomization
  description: Measured by standard 12-lead ECG
  measure: Change from baseline in QT interval
  time frame: 7 days post-randomization
  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)
  measure: Change from baseline in blood pressure
  time frame: 7 days post-randomization
  description: Blood pressure (systolic and diastolic) is measured using an automatic device
  measure: Change from baseline in heart rate
  time frame: 7 days post-randomization
  description: Heart rate is measured using an automatic device
  measure: Change from baseline in body temperature
  time frame: 7 days post-randomization
  description: Measurement of tympanic temperature
  measure: Change from baseline in perihematomal oedema (PHO) and haemorrhage volumes
  time frame: 10 days post-randomization
  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.
  measure: Measurement of the effect of Ir-CPI on the activated Partial Thromboplastin Time (aPTT)
  time frame: 7 days post-randomization
  description: Activated partial thromboplastin time (aPTT) will be used as a pharmacodynamic marker
  measure: Measurement of the effect of Ir-CPI on the inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities
  time frame: 7 days post-randomization
  description: The inhibition of Factor XI (FXI) and Factor XII (FXII) procoagulant activities will be assessed to support the aPTT dynamics
  measure: Change from baseline in Ir-CPI plasma concentrations
  time frame: 7 days post-randomization
  arm group label: Ir-CPI
  arm group type: Experimental
  description: Ir-CPI will be administered on top of standard of care
  arm group label: Standard care
  arm group type: No Intervention
  description: Only standard of care
  intervention type: Drug
  intervention name: Ir-CPI
  description: Participants receive a single intravenous dose of Ir-CPI during 48 hours
  arm group label: Ir-CPI
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Charlotte Corbisier
  phone: +32 (0)472 21 01 20
  email: charlotte.corbisier@bioxodes.com
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: Belgium
  responsible party type: Sponsor
  mesh term: Cerebral Hemorrhage
  mesh term: Hemorrhage
  sharing ipd: No