<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/NCT03017547</url>
  </required_header>
  <id_info>
    <org_study_id>AACTT01</org_study_id>
    <nct_id>NCT03017547</nct_id>
  </id_info>
  <brief_title>A Phase 2 Study of IC14 in Acute Respiratory Distress Syndrome</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Preliminary Efficacy Study of IC14 in Acute Respiratory Distress Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Implicit Bioscience</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Implicit Bioscience</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Acute Respiratory Distress Syndrome (ARDS) patients will be randomized to receive either IC14&#xD;
      (a single dose of 4 mg/kg followed by 2 mg/kg on Days 2-4) or placebo. Study participation&#xD;
      will be for a total of 28 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 160 patients with ARDS will be randomized to receive either IC14 at a dosage of 4 mg/kg&#xD;
      on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 or placebo for 4 days beginning&#xD;
      within 48 hours of meeting inclusion criteria. Study participation will be for 28 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    seeking funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">June 2019</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">June 2020</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>28 days</time_frame>
    <description>The number of toxicities and adverse events that are attributable to treatment. The safety parameters will include an evaluation of the clinical signs and symptoms from the history and physical exam, vital signs, adverse events, and laboratory findings. Immunogenicity studies will measure antibodies against IC14.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ventilator-free days</measure>
    <time_frame>28 days</time_frame>
    <description>The number of days alive and free of mechanical ventilation through Day 28.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in ARDS biologic markers.</measure>
    <time_frame>28 days</time_frame>
    <description>Change in plasma IL-8, sTNFR1, IL-6 from Day 0 to Day 4&#xD;
Change in alveolar neutrophils and total protein from Day 0 to Day 4</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>IC14</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IC14 4 mg/kg IV on Study Day 1, then IC14 2 mg/kg IV once daily on Study Days 2-4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo IV once daily on Study Day 1-4</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IC14</intervention_name>
    <description>Blocks CD14 signalling which is responsible for disease pathogenesis in ARDS</description>
    <arm_group_label>IC14</arm_group_label>
    <other_name>monoclonal antibody against CD14</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>sterile normal saline for infusion</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ICU admission&#xD;
&#xD;
          2. Age 18-70 years&#xD;
&#xD;
          3. Presence of a known ARDS clinical risk within 7 days of onset:&#xD;
&#xD;
               1. Pneumonia&#xD;
&#xD;
               2. Sepsis&#xD;
&#xD;
               3. Trauma&#xD;
&#xD;
               4. Aspiration&#xD;
&#xD;
               5. Pancreatitis&#xD;
&#xD;
          4. Presence of ARDS (per Berlin criteria) defined as follows:&#xD;
&#xD;
               1. Acute onset (&lt;48 hours)&#xD;
&#xD;
               2. PaO2/FiO2&lt;300 on PEEP≥5&#xD;
&#xD;
               3. Bilateral opacities consistent with pulmonary edema on frontal chest radiograph&#xD;
                  not fully explained by effusions, lobar/lung collapse, or nodules.&#xD;
&#xD;
               4. Requirement for positive pressure ventilation via endotracheal tube&#xD;
&#xD;
          5. Anticipated duration of mechanical ventilation &gt;48 hrs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treatment with a drug or device within the last 30 days that has not received&#xD;
             regulatory approval at the time of study entry&#xD;
&#xD;
          2. Intubation for cardiopulmonary arrest&#xD;
&#xD;
          3. Do-not-attempt resuscitation (DNAR) status&#xD;
&#xD;
          4. Intubation for status asthmaticus, pulmonary embolus, myocardial infarction&#xD;
&#xD;
          5. Anticipated survival &lt;48 hours from intubation&#xD;
&#xD;
          6. Anticipated survival &lt;28 days due to pre-existing medical condition&#xD;
&#xD;
          7. Significant pre-existing organ dysfunction&#xD;
&#xD;
               1. Lung: Currently receiving home oxygen therapy as documented in medical record&#xD;
&#xD;
               2. Heart: Pre-existing congestive heart failure defined as an ejection fraction &lt;20%&#xD;
                  as documented in the medical record&#xD;
&#xD;
               3. Renal: Chronic renal failure requiring renal replacement therapy&#xD;
&#xD;
               4. Liver: Severe chronic liver disease defined as Child-Pugh Class C&#xD;
&#xD;
          8. Pre-existing, ongoing immunosuppression&#xD;
&#xD;
               1. Solid organ transplant recipient&#xD;
&#xD;
               2. Chronic high-dose corticosteroids (equivalent to &gt;20 mg/prednisone/day for &gt;14&#xD;
                  days in the last 30 days)&#xD;
&#xD;
               3. Oncolytic drug therapy within the past 14 days&#xD;
&#xD;
               4. Known HIV positive with CD4 count &lt;200 cells/mm3&#xD;
&#xD;
          9. Current treatment with Enbrel® (etanercept), Remicade® (infliximab), Humira®&#xD;
             (adalimumab), Cimzia® (certolizumab), or Simponi® (golimumab), Kineret® (anakinra), or&#xD;
             Arcalyst® (rilonacept)&#xD;
&#xD;
         10. Pregnancy&#xD;
&#xD;
         11. History of hypersensitivity or idiosyncratic reaction to IC14&#xD;
&#xD;
         12. Deprivation of freedom by administrative or court order&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jan Agosti, MD</last_name>
    <role>Study Director</role>
    <affiliation>Implicit Bioscience</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>March 12, 2019</last_update_submitted>
  <last_update_submitted_qc>March 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_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/NCT03017547
org study id: AACTT01
nct id: NCT03017547
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Acute Respiratory Distress Syndrome (ARDS) patients will be randomized to receive either IC14
      (a single dose of 4 mg/kg followed by 2 mg/kg on Days 2-4) or placebo. Study participation
      will be for a total of 28 days.
Up to 160 patients with ARDS will be randomized to receive either IC14 at a dosage of 4 mg/kg
      on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 or placebo for 4 days beginning
      within 48 hours of meeting inclusion criteria. Study participation will be for 28 days.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety
time frame: 28 days
description: The number of toxicities and adverse events that are attributable to treatment. The safety parameters will include an evaluation of the clinical signs and symptoms from the history and physical exam, vital signs, adverse events, and laboratory findings. Immunogenicity studies will measure antibodies against IC14.
measure: Ventilator-free days
time frame: 28 days
description: The number of days alive and free of mechanical ventilation through Day 28.
measure: Change in ARDS biologic markers.
time frame: 28 days
description: Change in plasma IL-8, sTNFR1, IL-6 from Day 0 to Day 4
Change in alveolar neutrophils and total protein from Day 0 to Day 4
arm group label: IC14
arm group type: Experimental
description: IC14 4 mg/kg IV on Study Day 1, then IC14 2 mg/kg IV once daily on Study Days 2-4.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo IV once daily on Study Day 1-4
intervention type: Drug
intervention name: IC14
description: Blocks CD14 signalling which is responsible for disease pathogenesis in ARDS
arm group label: IC14
other name: monoclonal antibody against CD14
intervention type: Other
intervention name: Placebo
description: sterile normal saline for infusion
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jan Agosti, MD
role: Study Director
affiliation: Implicit Bioscience
country: United States
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome