<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/NCT04414631</url>
  </required_header>
  <id_info>
    <org_study_id>2020-01252; me20Osthoff3</org_study_id>
    <nct_id>NCT04414631</nct_id>
  </id_info>
  <brief_title>Conestat Alfa in the Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19</brief_title>
  <official_title>Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19: a Randomized, Parallel-group, Open-label, Multi-center Pilot Trial (PROTECT-COVID-19).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pharming Technologies B.V.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</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 aim of this study is to analyze if administration of conestat alfa for 72 hours in&#xD;
      addition to standard of care (SOC) in patients hospitalized with non-critical SARS-CoV-2&#xD;
      pneumonia (WHO Ordinal Scale Score 3 or 4) reduces the risk of disease progression to Acute&#xD;
      Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Systemic hyperinflammation is a hallmark of more severe stages of COVID-19 leading to acute&#xD;
      respiratory distress syndrome, mechanical ventilation and ultimately death. In this stage,&#xD;
      COVID-19 is associated with a decrease in suppressor and regulatory T cell counts and an&#xD;
      extensive release of proinflammatory cytokines and biomarkers called a cytokine storm, which&#xD;
      is thought to be the major driver of severe pneumonia caused by SARS-CoV-2. C1 esterase&#xD;
      inhibitor (C1INH) is a member of the serpin superfamily of serine-protease inhibitors and is&#xD;
      a strong inhibitor of the complement System (CS) and the kinin-kallikrein (KK) System.&#xD;
      Conestat alfa is a recombinant human C1INH, that shares an identical protein structure with&#xD;
      plasma-derived C1INH. The rationale of the current trial is based upon the following&#xD;
      assumptions: In the context of COVID-19, conestat alfa treatment may 1) dampen uncontrolled&#xD;
      complement activation and collateral lung damage and 2) reduce capillary leakage and&#xD;
      subsequent pulmonary edema by direct inhibition of KK system. The aim of this study is to&#xD;
      analyze administration of conestat alfa for 72 hours in addition to standard of care in&#xD;
      patients hospitalized with non-critical SARS-CoV-2 pneumonia (WHO Ordinal Scale Score 3 or 4)&#xD;
      and its association with clinical severity on day 7 after inclusion and the risk of disease&#xD;
      progression to Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Aim to enroll 120 patients deemed not sufficient to show a difference in the primary outcome&#xD;
    measure. Standard of care treatment recently changed in Switzerland adding further&#xD;
    heterogeneity to trial population when including future participants.&#xD;
  </why_stopped>
  <start_date type="Actual">August 6, 2020</start_date>
  <completion_date type="Actual">September 15, 2021</completion_date>
  <primary_completion_date type="Actual">September 15, 2021</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>
    <intervention_model_description>Randomized, open-label, parallel-group, controlled, multi-center clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease severity</measure>
    <time_frame>on day 7</time_frame>
    <description>Disease severity on the 7-point Ordinal World Health Organization (WHO) scale (for the current study, score 0 will be omitted and score 6 and 7 will be combined). The ordinal scale measures illness severity over time. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to clinical improvement</measure>
    <time_frame>within 14 days after enrolment</time_frame>
    <description>Time to clinical improvement (time from randomisation to an improvement of two points on the seven-category WHO ordinal scale or live discharge from hospital, whichever came first)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants alive and not having required invasive or non-invasive ventilation</measure>
    <time_frame>at 14 days after enrolment</time_frame>
    <description>Proportion of participants alive and not having required invasive or non-invasive ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with an ALI (defined by PaO2/FiO2 ratio of &lt;300mmHg)</measure>
    <time_frame>within 14 days after enrolment</time_frame>
    <description>Proportion of subjects with an ALI (defined by PaO2/FiO2 ratio of &lt;300mmHg)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in the ordinal WHO scale</measure>
    <time_frame>from baseline over 14 days</time_frame>
    <description>Changes in the ordinal WHO scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Length of hospital stay in survivors</measure>
    <time_frame>until day 28</time_frame>
    <description>Length of hospital stay in survivors</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants progressing to mechanical ventilation</measure>
    <time_frame>on day 7 and day 14</time_frame>
    <description>Proportion of participants progressing to mechanical ventilation</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants requiring ICU treatment</measure>
    <time_frame>on day 7 and 14</time_frame>
    <description>Proportion of participants requiring ICU treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Length of ICU stay</measure>
    <time_frame>until day 28</time_frame>
    <description>Length of ICU stay</description>
  </other_outcome>
  <other_outcome>
    <measure>28 Ventilator-free days</measure>
    <time_frame>until day 28</time_frame>
    <description>28 Ventilator-free days</description>
  </other_outcome>
  <other_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>time from randomisation to death within four weeks</time_frame>
    <description>All-cause mortality</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in biomarker level CRP (mg/l)</measure>
    <time_frame>until day 14</time_frame>
    <description>Changes in biomarker level CRP</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in biomarker level LDH (U/l)</measure>
    <time_frame>until day 14</time_frame>
    <description>Changes in biomarker level LDH</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in biomarker level D- Dimer (yg/ml)</measure>
    <time_frame>until day 14</time_frame>
    <description>Changes in biomarker level D-Dimer</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in biomarker level Ferritin (ng/ml)</measure>
    <time_frame>until day 14</time_frame>
    <description>Changes in biomarker level Ferritin</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in biomarker level Interleukin 6 (IL- 6) (pg/ml)</measure>
    <time_frame>until day 14</time_frame>
    <description>Changes in biomarker level IL-6</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in lymphocyte count (cells per microliter of blood)</measure>
    <time_frame>until day 14</time_frame>
    <description>Changes in lymphocyte count</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to virological clearance of SARS-CoV-2 by PCR from upper or lower respiratory tract samples</measure>
    <time_frame>time from enrolment to first of 2 negative assays at least 12 hours apart</time_frame>
    <description>Time to virological clearance of SARS-CoV-2 by PCR from upper or lower respiratory tract samples</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of patients receiving additional anti-inflammatory treatment such as tocilizumab or immunoglobulins</measure>
    <time_frame>within 14 days</time_frame>
    <description>Proportion of patients receiving additional anti-inflammatory treatment such as tocilizumab or immunoglobulins</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to defervescence (temperature &lt;38.0°C)</measure>
    <time_frame>sustained for at least 48 hours</time_frame>
    <description>Time to defervescence (temperature &lt;38.0°C)</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to clinical improvement (defervescence, normalization of oxygen saturation (&gt;93%) and respiratory rate) until day 28</measure>
    <time_frame>until day 28</time_frame>
    <description>Time to clinical improvement (defervescence, normalization of oxygen saturation (&gt;93%) and respiratory rate)</description>
  </other_outcome>
  <other_outcome>
    <measure>Duration of supplemental oxygen</measure>
    <time_frame>until day 28</time_frame>
    <description>Duration of supplemental oxygen</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in pharmacokinetics of conestat alfa</measure>
    <time_frame>at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date</time_frame>
    <description>Peak serum concentration of conestat alfa will be measured</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in pharmacodynamics of conestat alfa (C1-inhibitor (CI-INH) concentration)</measure>
    <time_frame>at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date</time_frame>
    <description>Change in pharmacodynamics of conestat alfa (C1-inhibitor (CI-INH) concentration)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Coronavirus Infections</condition>
  <arm_group>
    <arm_group_label>active treatment arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>treatment with conestat alfa in addition to standarf of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care treatment arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care treatment established at the centers</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Conestat alfa</intervention_name>
    <description>Conestat alfa (8400 Units (U) followed by 4200 U every 8 hours, 9 administrations in total) will be administered as a slow intravenous injection (5-10 minutes) over a 72 hour period.</description>
    <arm_group_label>active treatment arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed Consent as documented by signature&#xD;
&#xD;
          -  admitted to the hospital because of confirmed (by a positive SARS-CoV-2 PCR result)&#xD;
             COVID-19 infection&#xD;
&#xD;
          -  evidence of pulmonary involvement on CT scan or X-ray of the chest (e.g. ground glass&#xD;
             opacities)&#xD;
&#xD;
          -  symptom onset within the previous 10 days OR shortness of breath within the previous 5&#xD;
             days. Symptoms include fever or one respiratory symptom (patients presenting later may&#xD;
             have already progressed to an inflammatory state that is potentially not amenable to&#xD;
             C1INH treatment). Respiratory symptoms include cough, sore throat, hemoptysis,&#xD;
             shortness of breath, runny nose, or chest pain.&#xD;
&#xD;
          -  expected to remain an inpatient over the next three calender days from time of&#xD;
             enrolment&#xD;
&#xD;
          -  at least one additional risk factor for progression to mechanical ventilation: 1)&#xD;
             arterial hypertension, 2) &gt;50 years, 3) obesity (BMI&gt;30.0 kg/m2), 4) cardiovascular&#xD;
             disease, 5) chronic pulmonary disease, 7) chronic renal disease, 6) C-reactive protein&#xD;
             of &gt;35mg/L, 7) oxygen saturation at rest in ambient air of &lt;94%. Cardiovascular&#xD;
             disease includes a history of coronary artery disease, cerebrovascular disease,&#xD;
             peripheral artery disease, rheumatic heart disease, congenital heart disease and of&#xD;
             recent (&lt; 3 months) deep vein thrombosis or pulmonary embolism. Chronic pulmonary&#xD;
             disease includes a history of chronic obstructive pulmonary disease, asthma,&#xD;
             occupational lung disease, interstitial lung disease or of pulmonary hypertension.&#xD;
             Chronic renal disease is defined as a history of an estimated glomerular filtration&#xD;
             rate (according to the Chronic Kidney Disease Epidemiology Collaboration equation) &lt;&#xD;
             60ml/min/1.73 m2 for at least three months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to the class of drugs under study (C1 esterase inhibitor), e.g.&#xD;
             known hypersensitivity or allergy to class of drugs or the investigational product&#xD;
&#xD;
          -  Treatment with tocilizumab or another Il-6R or Il-6 inhibitor before enrolment&#xD;
&#xD;
          -  History or suspicion of allergy to rabbits&#xD;
&#xD;
          -  Women who are pregnant or breast feeding&#xD;
&#xD;
          -  Active or planned treatment with any other complement inhibitor&#xD;
&#xD;
          -  Liver cirrhosis (any Child-Pugh score)&#xD;
&#xD;
          -  Incapacity or inability to provide informed consent&#xD;
&#xD;
          -  Currently admitted to an ICU or expected admission within the next 24 hours&#xD;
&#xD;
          -  Currently receiving invasive or non-invasive ventilation (with the exception of&#xD;
             high-flow oxygen therapy).&#xD;
&#xD;
          -  In the opinion of the treating time, death is deemed to be imminent and inevitable&#xD;
             within the next 24 hours&#xD;
&#xD;
          -  Participation in another study with investigational drug within the 30 days preceding&#xD;
             and during the present study with the following exemptions: 1) participation in&#xD;
             COVID-19 drug trials started at least 48 hours before admission (e.g. postexposure&#xD;
             prophylaxis with hydroxychloroquine) and 2) participation in COVID-19 drug trials&#xD;
             during ICU admission&#xD;
&#xD;
          -  Previous enrolment into the current study&#xD;
&#xD;
          -  Enrolment of the investigator, his/her family members, employees and other dependent&#xD;
             persons&#xD;
&#xD;
          -  Any uncontrolled or significant concurrent illness that would put the patient at a&#xD;
             greater risk or limit compliance with the study requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Osthoff, PD Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Basel, Division of Internal Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Práxis Pesquisa Medica</name>
      <address>
        <city>São Paulo</city>
        <zip>09090-790</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario &quot;Dr. José Eleiterio González&quot;, Colinia Mitras Centro</name>
      <address>
        <city>Monterey</city>
        <state>Nuevo Leon Mexico</state>
        <zip>C.P 64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Basel, Division of Internal Medicine</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital St. Gallen, Klinik für Infektiologie/Spitalhygiene</name>
      <address>
        <city>St. Gallen</city>
        <zip>9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stadtspital Triemli, Departement Innere Medizin</name>
      <address>
        <city>Zürich</city>
        <zip>8063</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Mexico</country>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>November 1, 2021</last_update_submitted>
  <last_update_submitted_qc>November 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Systemic hyperinflammation</keyword>
  <keyword>cytokine storm</keyword>
  <keyword>complement system</keyword>
  <keyword>kinin-kallikrein system</keyword>
  <keyword>C1 esterase inhibitor</keyword>
  <keyword>Conestat alfa</keyword>
  <keyword>Coronavirus Disease 19 (COVID-19)</keyword>
  <keyword>Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Complement C1 Inhibitor Protein</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04414631
org study id: 2020-01252; me20Osthoff3
nct id: NCT04414631
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to analyze if administration of conestat alfa for 72 hours in
      addition to standard of care (SOC) in patients hospitalized with non-critical SARS-CoV-2
      pneumonia (WHO Ordinal Scale Score 3 or 4) reduces the risk of disease progression to Acute
      Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).
Systemic hyperinflammation is a hallmark of more severe stages of COVID-19 leading to acute
      respiratory distress syndrome, mechanical ventilation and ultimately death. In this stage,
      COVID-19 is associated with a decrease in suppressor and regulatory T cell counts and an
      extensive release of proinflammatory cytokines and biomarkers called a cytokine storm, which
      is thought to be the major driver of severe pneumonia caused by SARS-CoV-2. C1 esterase
      inhibitor (C1INH) is a member of the serpin superfamily of serine-protease inhibitors and is
      a strong inhibitor of the complement System (CS) and the kinin-kallikrein (KK) System.
      Conestat alfa is a recombinant human C1INH, that shares an identical protein structure with
      plasma-derived C1INH. The rationale of the current trial is based upon the following
      assumptions: In the context of COVID-19, conestat alfa treatment may 1) dampen uncontrolled
      complement activation and collateral lung damage and 2) reduce capillary leakage and
      subsequent pulmonary edema by direct inhibition of KK system. The aim of this study is to
      analyze administration of conestat alfa for 72 hours in addition to standard of care in
      patients hospitalized with non-critical SARS-CoV-2 pneumonia (WHO Ordinal Scale Score 3 or 4)
      and its association with clinical severity on day 7 after inclusion and the risk of disease
      progression to Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, open-label, parallel-group, controlled, multi-center clinical trial
primary purpose: Treatment
masking: None (Open Label)
measure: Disease severity
time frame: on day 7
description: Disease severity on the 7-point Ordinal World Health Organization (WHO) scale (for the current study, score 0 will be omitted and score 6 and 7 will be combined). The ordinal scale measures illness severity over time. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19.
measure: Time to clinical improvement
time frame: within 14 days after enrolment
description: Time to clinical improvement (time from randomisation to an improvement of two points on the seven-category WHO ordinal scale or live discharge from hospital, whichever came first)
measure: Proportion of participants alive and not having required invasive or non-invasive ventilation
time frame: at 14 days after enrolment
description: Proportion of participants alive and not having required invasive or non-invasive ventilation
measure: Proportion of subjects with an ALI (defined by PaO2/FiO2 ratio of <300mmHg)
time frame: within 14 days after enrolment
description: Proportion of subjects with an ALI (defined by PaO2/FiO2 ratio of <300mmHg)
measure: Changes in the ordinal WHO scale
time frame: from baseline over 14 days
description: Changes in the ordinal WHO scale
measure: Length of hospital stay in survivors
time frame: until day 28
description: Length of hospital stay in survivors
measure: Proportion of participants progressing to mechanical ventilation
time frame: on day 7 and day 14
description: Proportion of participants progressing to mechanical ventilation
measure: Proportion of participants requiring ICU treatment
time frame: on day 7 and 14
description: Proportion of participants requiring ICU treatment
measure: Length of ICU stay
time frame: until day 28
description: Length of ICU stay
measure: 28 Ventilator-free days
time frame: until day 28
description: 28 Ventilator-free days
measure: All-cause mortality
time frame: time from randomisation to death within four weeks
description: All-cause mortality
measure: Changes in biomarker level CRP (mg/l)
time frame: until day 14
description: Changes in biomarker level CRP
measure: Changes in biomarker level LDH (U/l)
time frame: until day 14
description: Changes in biomarker level LDH
measure: Changes in biomarker level D- Dimer (yg/ml)
time frame: until day 14
description: Changes in biomarker level D-Dimer
measure: Changes in biomarker level Ferritin (ng/ml)
time frame: until day 14
description: Changes in biomarker level Ferritin
measure: Changes in biomarker level Interleukin 6 (IL- 6) (pg/ml)
time frame: until day 14
description: Changes in biomarker level IL-6
measure: Changes in lymphocyte count (cells per microliter of blood)
time frame: until day 14
description: Changes in lymphocyte count
measure: Time to virological clearance of SARS-CoV-2 by PCR from upper or lower respiratory tract samples
time frame: time from enrolment to first of 2 negative assays at least 12 hours apart
description: Time to virological clearance of SARS-CoV-2 by PCR from upper or lower respiratory tract samples
measure: Proportion of patients receiving additional anti-inflammatory treatment such as tocilizumab or immunoglobulins
time frame: within 14 days
description: Proportion of patients receiving additional anti-inflammatory treatment such as tocilizumab or immunoglobulins
measure: Time to defervescence (temperature <38.0°C)
time frame: sustained for at least 48 hours
description: Time to defervescence (temperature <38.0°C)
measure: Time to clinical improvement (defervescence, normalization of oxygen saturation (>93%) and respiratory rate) until day 28
time frame: until day 28
description: Time to clinical improvement (defervescence, normalization of oxygen saturation (>93%) and respiratory rate)
measure: Duration of supplemental oxygen
time frame: until day 28
description: Duration of supplemental oxygen
measure: Change in pharmacokinetics of conestat alfa
time frame: at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date
description: Peak serum concentration of conestat alfa will be measured
measure: Change in pharmacodynamics of conestat alfa (C1-inhibitor (CI-INH) concentration)
time frame: at baseline, day 1, day 3, day 7, day 10 (during admission) and day 14 (1/- 2days) or discharge date
description: Change in pharmacodynamics of conestat alfa (C1-inhibitor (CI-INH) concentration)
arm group label: active treatment arm
arm group type: Active Comparator
description: treatment with conestat alfa in addition to standarf of care
arm group label: Standard of care treatment arm
arm group type: No Intervention
description: Standard of care treatment established at the centers
intervention type: Drug
intervention name: Conestat alfa
description: Conestat alfa (8400 Units (U) followed by 4200 U every 8 hours, 9 administrations in total) will be administered as a slow intravenous injection (5-10 minutes) over a 72 hour period.
arm group label: active treatment arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Michael Osthoff, PD Dr. med.
role: Principal Investigator
affiliation: University Hospital Basel, Division of Internal Medicine
facility: 
facility: 
facility: 
facility: 
facility: 
country: Brazil
country: Mexico
country: Switzerland
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Complement C1 Inhibitor Protein