<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/NCT02246595</url>
  </required_header>
  <id_info>
    <org_study_id>IFX-1-P2.1</org_study_id>
    <secondary_id>2013-001037-40</secondary_id>
    <nct_id>NCT02246595</nct_id>
  </id_info>
  <brief_title>Studying Complement Inhibition in Early, Newly Developing Septic Organ Dysfunction</brief_title>
  <acronym>SCIENS</acronym>
  <official_title>A Phase II Randomized, Placebo-controlled, Double-blind, Dose Controlled Trial in Patients Suffering From Early, Newly Developing Abdominal or Pulmonary Derived Septic Organ Dysfunction to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and to Estimate Efficacy of the New Humanized Monoclonal i.v. Administered Antibody CaCP29</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>InflaRx GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>InflaRx GmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial enrolls patients with early severe sepsis or septic shock displaying at least one&#xD;
      newly developed organ dysfunction and showing clinical evidence of pulmonary or abdominal&#xD;
      infection. The primary goal of the trial is to assess the pharmacokinetics and&#xD;
      pharmacodynamics of the new monoclonal antibody CaCP29 and to characterize safety and&#xD;
      tolerability as well as evaluate parameters of efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma Concentration of CaCP29</measure>
    <time_frame>0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28</time_frame>
    <description>Pharmacokinetic measures include&#xD;
Plasma concentration over time&#xD;
Maximum observed concentration per infusion&#xD;
Concentration measured immediately before next dosing&#xD;
Area under the curve of plasma concentration per infusion&#xD;
Mean concentration per infusion&#xD;
Terminal phase half-life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess the pharmacodynamic (PD) effects of CaCP29 on the change from baseline in plasma concentrations of C5a</measure>
    <time_frame>0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety variables will be summarized using descriptive statistics based on adverse event collection</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibodies (ADA)</measure>
    <time_frame>28 days or hospital discharge</time_frame>
    <description>The development of ADA will be described by:&#xD;
Number of patients with detection of anti-drug antibody (ADA)&#xD;
Number of patients with detection of ADA at each time point measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality rate</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Morbidity</measure>
    <time_frame>daily</time_frame>
    <description>Mean SOFA until Day 10&#xD;
Modified mean SOFA until day 10 (calculated by omitting the Central Nervous System sub-score and calculating the renal subscore without taking urine output into consideration)&#xD;
Mean SOFA Sub-scores until Day 10&#xD;
Days on ICU until Day 28&#xD;
Number of patients ventilated until Day 14&#xD;
Ventilator-free days until Day 14&#xD;
Numbers of patients with renal replacement therapy (RRT) until Day 14&#xD;
RRT-free days until Day 14&#xD;
Numbers of patients with administration of vasopressor until Day 14&#xD;
Vasopressor-free days until Day 14&#xD;
Days without antimicrobial therapy (AMT) until Day 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluid balance</measure>
    <time_frame>28 days or ICU discharge</time_frame>
    <description>Mean daily total fluid intake until Day 28 (maximal until ICU discharge)&#xD;
Mean daily total fluid output until Day 28 (maximal until ICU discharge)&#xD;
Mean daily fluid balance until Day 28 (maximal until ICU discharge)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in routine laboratory parameters as compared to baseline</measure>
    <time_frame>Days 1, 2, 3, 4, 5, 8, 13, 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ECG as compared to baseline</measure>
    <time_frame>Days 2, 4, 8, 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in vital signs as compared to baseline</measure>
    <time_frame>Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Severe Sepsis</condition>
  <condition>Septic Shock</condition>
  <arm_group>
    <arm_group_label>CaCP29</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>dose escalating i.v. administration of CaCP29 (verum)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>dose escalation mimicing i.v. placebo treatment:</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CaCP29</intervention_name>
    <arm_group_label>CaCP29</arm_group_label>
    <other_name>IFX-1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria at screening:&#xD;
&#xD;
          1. Male or female patients &gt;= 18 years old&#xD;
&#xD;
          2. Written informed consent&#xD;
&#xD;
          3. Occurrence of at least two criteria of a systemic inflammatory response syndrome&#xD;
             (SIRS) not explained by other reasons. These criteria should be present within 12&#xD;
             hours prior to screening&#xD;
&#xD;
          4. Suspected or confirmed abdominal or pulmonary infection at screening&#xD;
&#xD;
          5. Broad spectrum i.v. antimicrobial therapy to treat abdominal or pulmonary infection&#xD;
&#xD;
          6. At least one of the following acute organ dysfunctions due to sepsis. Each organ&#xD;
             dysfunction must have occurred within 12 hours prior to screening, cannot mainly be&#xD;
             explained by other disease processes than sepsis and is judged by the investigator as&#xD;
             being caused or directly related to an abdominal or pulmonary infectious focus:&#xD;
&#xD;
               1. respiratory&#xD;
&#xD;
               2. renal&#xD;
&#xD;
               3. hematologic&#xD;
&#xD;
               4. metabolic&#xD;
&#xD;
               5. cardiovascular (occurred within the last three hours)&#xD;
&#xD;
          7. Reasonable likelihood that administration of study drug can be started within 3.5&#xD;
             hours after start of screening process&#xD;
&#xD;
        Key Exclusion Criteria at screening:&#xD;
&#xD;
          1. Sepsis of other primary cause than pulmonary or abdominal source&#xD;
&#xD;
          2. Weight &gt; 130 kg at screening&#xD;
&#xD;
          3. Any other disease and condition that is likely to interfere with evaluation of study&#xD;
             product, outcome assessment or satisfactory conduct of the study&#xD;
&#xD;
          4. Patients receiving the following concomitant medication within 14 days prior to&#xD;
             screening:&#xD;
&#xD;
               1. Calcineurin inhibitors (e.g., ciclosporine, tacrolimus)&#xD;
&#xD;
               2. Proliferation inhibitors (e.g., everolimus, sirolimus)&#xD;
&#xD;
               3. Anti-metabolites (e.g., mycophenolate, mycophenolic acid, azathioprine)&#xD;
&#xD;
               4. High dose corticosteroids (e.g., &gt; 50mg prednisolon per day or equivalent)&#xD;
&#xD;
          5. Patients receiving high dose immunoglobulins within 3 months prior to screening&#xD;
&#xD;
          6. Patients with following abnormal laboratory result: Neutrocytopenia with neutrophil&#xD;
             count &lt; 1,000/mm3 unless likely due to sepsis&#xD;
&#xD;
          7. General criteria:&#xD;
&#xD;
               1. Pregnant (in women of childbearing potential an urine pregnancy test has to be&#xD;
                  performed) or breast-feeding women&#xD;
&#xD;
               2. Women with childbearing potential (defined as within two years of their last&#xD;
                  menstruation) not willing to practice appropriate contraceptive measures (e.g.,&#xD;
                  implanon, injections, oral contraceptives, intrauterine devices, partner with&#xD;
                  vasectomy, abstinence) while participating in the trial&#xD;
&#xD;
               3. Participation in any interventional clinical trial within the last three months&#xD;
&#xD;
               4. Prior participation in this clinical trial&#xD;
&#xD;
               5. Patient is chronically bed-bound prior to the onset of sepsis&#xD;
&#xD;
               6. Known intravenous drug abuse&#xD;
&#xD;
               7. Employee at the study site, spouse/partner or relative of any study staff (e.g.,&#xD;
                  investigator, sub-investigators, or study nurse) or relationship to the sponsor&#xD;
&#xD;
               8. No commitment to full aggressive life support (e.g., do not resuscitate order)&#xD;
&#xD;
        Inclusion Criteria at randomisation:&#xD;
&#xD;
          1. At least one of the sepsis related organ dysfunction detected at screening is still&#xD;
             present&#xD;
&#xD;
          2. Current treatment with broad spectrum i.v. antibiotics has been started or is ongoing&#xD;
&#xD;
        Exclusion Criteria at randomisation:&#xD;
&#xD;
          1. Time frame between detection of a non cardiovascular organ dysfunction and start of&#xD;
             randomization procedure is more than 15 hours&#xD;
&#xD;
          2. Time frame between detection of a cardiovascular organ dysfunction and start of&#xD;
             randomization is more than six hours&#xD;
&#xD;
          3. Organ dysfunctions are unlikely to be persistent for next three hours&#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_official>
    <last_name>Michael Bauer, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Jena</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Aachen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Augsburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Bad Saarow</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Greifswald</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Göttingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Jena</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Kiel</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Study Site</name>
      <address>
        <city>Oldenburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <last_update_submitted>April 22, 2016</last_update_submitted>
  <last_update_submitted_qc>April 22, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 25, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sepsis</keyword>
  <keyword>Severe Sepsis</keyword>
  <keyword>Septic Shock</keyword>
  <keyword>Systemic Inflammatory Response Syndrome</keyword>
  <keyword>Organ Dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Shock, Septic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vilobelimab</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/NCT02246595
org study id: IFX-1-P2.1
secondary id: 2013-001037-40
nct id: NCT02246595
lead sponsor: 
has dmc: Yes
The trial enrolls patients with early severe sepsis or septic shock displaying at least one
      newly developed organ dysfunction and showing clinical evidence of pulmonary or abdominal
      infection. The primary goal of the trial is to assess the pharmacokinetics and
      pharmacodynamics of the new monoclonal antibody CaCP29 and to characterize safety and
      tolerability as well as evaluate parameters of efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Plasma Concentration of CaCP29
time frame: 0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28
description: Pharmacokinetic measures include
Plasma concentration over time
Maximum observed concentration per infusion
Concentration measured immediately before next dosing
Area under the curve of plasma concentration per infusion
Mean concentration per infusion
Terminal phase half-life
measure: Assess the pharmacodynamic (PD) effects of CaCP29 on the change from baseline in plasma concentrations of C5a
time frame: 0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28
measure: Safety variables will be summarized using descriptive statistics based on adverse event collection
time frame: 28 days
measure: Anti-drug antibodies (ADA)
time frame: 28 days or hospital discharge
description: The development of ADA will be described by:
Number of patients with detection of anti-drug antibody (ADA)
Number of patients with detection of ADA at each time point measured
measure: All-cause mortality rate
time frame: 28 days
measure: Morbidity
time frame: daily
description: Mean SOFA until Day 10
Modified mean SOFA until day 10 (calculated by omitting the Central Nervous System sub-score and calculating the renal subscore without taking urine output into consideration)
Mean SOFA Sub-scores until Day 10
Days on ICU until Day 28
Number of patients ventilated until Day 14
Ventilator-free days until Day 14
Numbers of patients with renal replacement therapy (RRT) until Day 14
RRT-free days until Day 14
Numbers of patients with administration of vasopressor until Day 14
Vasopressor-free days until Day 14
Days without antimicrobial therapy (AMT) until Day 14
measure: Fluid balance
time frame: 28 days or ICU discharge
description: Mean daily total fluid intake until Day 28 (maximal until ICU discharge)
Mean daily total fluid output until Day 28 (maximal until ICU discharge)
Mean daily fluid balance until Day 28 (maximal until ICU discharge)
measure: Change in routine laboratory parameters as compared to baseline
time frame: Days 1, 2, 3, 4, 5, 8, 13, 28
measure: Change in ECG as compared to baseline
time frame: Days 2, 4, 8, 28
measure: Change in vital signs as compared to baseline
time frame: Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28
arm group label: CaCP29
arm group type: Active Comparator
description: dose escalating i.v. administration of CaCP29 (verum)
arm group label: Placebo
arm group type: Placebo Comparator
description: dose escalation mimicing i.v. placebo treatment:
intervention type: Biological
intervention name: CaCP29
arm group label: CaCP29
other name: IFX-1
intervention type: Biological
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Bauer, Prof. Dr.
role: Principal Investigator
affiliation: University Hospital Jena
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Sepsis
mesh term: Shock, Septic
mesh term: Vilobelimab