<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/NCT04481685</url>
  </required_header>
  <id_info>
    <org_study_id>IIT-2020-ATI-450-COVID-19</org_study_id>
    <nct_id>NCT04481685</nct_id>
  </id_info>
  <brief_title>A Trial of Aclaris Therapeutics, Inc. (ATI)-450 in Patients With Moderate-severe Novel Coronavirus Disease 2019 (COVID-19)</brief_title>
  <official_title>A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Kansas Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kansas Medical Center</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>
      COVID-19 morbidity and mortality has been associated with Cytokine Release Syndrome (CRS) and&#xD;
      Acute Respiratory Distress Syndrome (ARDS).&#xD;
&#xD;
      ATI-450 is an oral small molecule MAPKAPK2 (MK2) inhibitor that potently inhibits multiple&#xD;
      inflammatory cytokines.&#xD;
&#xD;
      The investigator hypothesizes that MK2 pathway blockade during active COVID-19 infection in&#xD;
      hospitalized participants will result in improvement in respiratory-failure free survival.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Actual">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">February 25, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Respiratory failure-free survival in participants with moderate-severe COVID-19 who are treated with ATI-450</measure>
    <time_frame>Study day 14</time_frame>
    <description>Participants medical record</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in 7 point-ordinal scale</measure>
    <time_frame>Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months</time_frame>
    <description>Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Proportion and time to participants with greater than 2 point improvement on the 7 point categorical scale. This scale measures illness severity over time and has a range of 0-7.&#xD;
0- Uninfected: No clinical or virological evidence of infection.&#xD;
1- Ambulatory: No limitation of activities.&#xD;
2- Ambulatory: Limitation of activities.&#xD;
3- Hospitalized, mild disease: Hospitalized, no oxygen.&#xD;
4- Hospitalized, mild disease: Oxygen by mask or nasal prongs.&#xD;
5- Hospitalized, severe disease: Non- invasive ventilation or high- flow oxygen.&#xD;
6- Hospitalized, severe disease: Intubation and mechanical ventilation.&#xD;
7- Hospitalized, severe disease: Ventilation + organ support; pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in oxygen saturation-normalization</measure>
    <time_frame>Baseline and continuous throughout hospitalization up to 14 days</time_frame>
    <description>Peripheral capillary pulse oximeter to measure: Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) ratio over time, sustainment of normalization in 24 hours, and relative shifts in SpO2/FiO2 categories (&lt;235, between 235 and 315, greater than 315) over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for advanced respiratory care</measure>
    <time_frame>Baseline and continuous throughout hospitalization up to 14 days</time_frame>
    <description>Derived from medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>Baseline and through day 60</time_frame>
    <description>Noted in participant medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of adverse events (AEs)</measure>
    <time_frame>Baseline through day 14 or at discharge &lt;day 14, at day 28, day 45 and day 60</time_frame>
    <description>CTCAE v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of serious adverse events (SAEs)</measure>
    <time_frame>Baseline through day 14 or at discharge &lt;day 14, at day 28, day 45 and day 60</time_frame>
    <description>CTCAE v5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with normalization of fever for 24 hours</measure>
    <time_frame>Baseline through day 14 or at discharge &lt;day 14</time_frame>
    <description>Standard daily temperature measurement and obtained from participant medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who develop new bacterial infection</measure>
    <time_frame>Continuous throughout hospitalization up to 14 days</time_frame>
    <description>Noted in participant medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants who develop new fungal infection</measure>
    <time_frame>Continuous throughout hospitalization up to 14 days</time_frame>
    <description>Noted in participant medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adult Respiratory distress Syndrome (ARDS2)</measure>
    <time_frame>From day 1 though day 14 or at discharge &lt;day 14</time_frame>
    <description>Noted in participant medical record</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum cytokine Interleukin (IL)-6</measure>
    <time_frame>Baseline, day 3, day 7 (or discharge &lt;day 7), day 14 (or discharge &gt;day 7 and &lt;day 14)</time_frame>
    <description>Serum collected from blood and assayed on Luminex panel performed by University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum cytokine IL-8</measure>
    <time_frame>Baseline, day 3, day 7 (or discharge &lt;day 7), day 14 (or discharge &gt;day 7 and &lt;day 14)</time_frame>
    <description>Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum cytokines IL-1β</measure>
    <time_frame>Baseline, day 3, day 7 (or discharge &lt;day 7), day 14 (or discharge &gt;day 7 and &lt;day 14)</time_frame>
    <description>Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum cytokine Tumor Necrosis Factor (TNF-α)</measure>
    <time_frame>Baseline, day 3, day 7 (or discharge &lt;day 7), day 14 (or discharge &gt;day 7 and &lt;day 14)</time_frame>
    <description>Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>ATI-450</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Treated with matched placebo, orally, twice daily for 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ATI-450</intervention_name>
    <description>50 mg (as determined from Phase I study) per dose. (100 mg per day). Up to a maximum of 14 days while inpatient. Patients discharged home or transferred to the intensive care unit (ICU) will be discontinued off drug permanently.</description>
    <arm_group_label>ATI-450</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo pill will be taken twice daily preferably spaced 12 hours apart.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to comprehend and be willing to sign the Institutional Review Board&#xD;
             (IRB)-approved subject informed consent form (ICF) prior to administration of any&#xD;
             study-related procedures, or consent from surrogate decision maker when the above&#xD;
             criteria cannot be met&#xD;
&#xD;
          -  Male or non-pregnant female adult ≥18 years of age at time of enrollment; female&#xD;
             patients must have a negative serum pregnancy test at study enrollment&#xD;
&#xD;
          -  Has laboratory-confirmed COVID-19 coronavirus infection as determined by polymerase&#xD;
             chain reaction (PCR), or other commercial or public health assay in oropharyngeal or&#xD;
             nasopharyngeal testing within 14 days of hospitalization. An additional 24-hour&#xD;
             COVID-19 PCR test will be performed at KUMC. Patients outside of KUMC will have their&#xD;
             samples sent to KUMC as a Central Lab for test processing&#xD;
&#xD;
          -  Hospitalized as a result of symptoms and signs related to COVID-19 infection, and ≤14&#xD;
             days since positive test&#xD;
&#xD;
          -  Evidence of hypoxic respiratory failure: SpO2≤93% on room air, or SpO2 &gt;93% requiring&#xD;
             ≥ 2 Liters (L) O2, or Pa02/Fi02 ratio &lt;300 Millimeter of Mercury (mmHg), or tachypnea&#xD;
             (respiratory rate &gt; 30 breaths/min)&#xD;
&#xD;
          -  Evidence of pulmonary involvement by: chest imaging or pulmonary exam&#xD;
&#xD;
          -  Previous use of hydroxychloroquine or chloroquine is allowed in this study&#xD;
&#xD;
          -  Adequate organ function per laboratory tests&#xD;
&#xD;
          -  Females of child-bearing potential and males with partners of child-bearing potential&#xD;
             must agree to practice sexual abstinence or to use the forms of contraception listed&#xD;
             in Child-Bearing Potential/Pregnancy section for the duration of study participation&#xD;
             and for 30 Days for females and 90 days for males following completion of therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to ATI-450&#xD;
&#xD;
          -  History or evidence of active or latent tuberculosis or recent exposure (within last&#xD;
             30d) to a person with active Tb&#xD;
&#xD;
          -  Evidence of active, untreated bacterial infection. Patients who are treated with&#xD;
             antibiotics for at least 72 hours, will become eligible for rescreening for trial&#xD;
             enrollment&#xD;
&#xD;
          -  Active use of immunosuppressant medication(s) (i.e. anti-rejection ,immunomodulators&#xD;
             or immunosuppressant drugs, including but not limited to IL-6 inhibitors, TNF&#xD;
             inhibitors, anti-IL-1 agents and Janus kinase (JAK) inhibitors within 5 half-lives or&#xD;
             30 days (whichever is longer) prior to randomization. (Use of&#xD;
             hydroxychloroquine/chloroquine should be discontinued)&#xD;
&#xD;
          -  Oncology patients who are on active chemotherapy or immunotherapy. However, oncology&#xD;
             patients who come off active therapy prior to enrollment and have absolute neutrophil&#xD;
             count (ANC) ≥1500/mmc are eligible for enrollment&#xD;
&#xD;
          -  Active participation in a concurrent COVID-19 clinical trial with investigative&#xD;
             medical drug therapies. However, co-enrollment for non-investigative drug therapies&#xD;
             will be allowed; use or re-purposing of FDA approved treatments will be considered at&#xD;
             the discretion of the medical monitor&#xD;
&#xD;
          -  In the opinion of the investigator, unlikely to survive for at least 48 hours from&#xD;
             screening or anticipate mechanical ventilation within 48 hours&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Prisoner&#xD;
&#xD;
          -  Intubation and ventilation at time of enrollment&#xD;
&#xD;
          -  Known history for HIV, hepatitis B or C infection. Patients with serologic evidence of&#xD;
             hepatitis B vaccination (hepatitis B surface antibody without the presence of&#xD;
             hepatitis B surface antigen) will be allowed to participate&#xD;
&#xD;
          -  History of a past or current medical condition that in the opinion of the treating&#xD;
             physician would compromise patient safety (e.g. uncontrolled HIV) by participation in&#xD;
             the study&#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>Gregory Gan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Kansas</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Deepika Polineni, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Kansas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>June 22, 2021</last_update_submitted>
  <last_update_submitted_qc>June 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2021</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>COVID-19</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>March 29, 2023</submitted>
    <returned>April 19, 2023</returned>
  </pending_results>
  <!-- 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/NCT04481685
org study id: IIT-2020-ATI-450-COVID-19
nct id: NCT04481685
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
COVID-19 morbidity and mortality has been associated with Cytokine Release Syndrome (CRS) and
      Acute Respiratory Distress Syndrome (ARDS).

      ATI-450 is an oral small molecule MAPKAPK2 (MK2) inhibitor that potently inhibits multiple
      inflammatory cytokines.

      The investigator hypothesizes that MK2 pathway blockade during active COVID-19 infection in
      hospitalized participants will result in improvement in respiratory-failure free survival.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Respiratory failure-free survival in participants with moderate-severe COVID-19 who are treated with ATI-450
time frame: Study day 14
description: Participants medical record
measure: Change in 7 point-ordinal scale
time frame: Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months
description: Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Proportion and time to participants with greater than 2 point improvement on the 7 point categorical scale. This scale measures illness severity over time and has a range of 0-7.
0- Uninfected: No clinical or virological evidence of infection.
1- Ambulatory: No limitation of activities.
2- Ambulatory: Limitation of activities.
3- Hospitalized, mild disease: Hospitalized, no oxygen.
4- Hospitalized, mild disease: Oxygen by mask or nasal prongs.
5- Hospitalized, severe disease: Non- invasive ventilation or high- flow oxygen.
6- Hospitalized, severe disease: Intubation and mechanical ventilation.
7- Hospitalized, severe disease: Ventilation + organ support; pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO).
measure: Change in oxygen saturation-normalization
time frame: Baseline and continuous throughout hospitalization up to 14 days
description: Peripheral capillary pulse oximeter to measure: Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) ratio over time, sustainment of normalization in 24 hours, and relative shifts in SpO2/FiO2 categories (<235, between 235 and 315, greater than 315) over time
measure: Need for advanced respiratory care
time frame: Baseline and continuous throughout hospitalization up to 14 days
description: Derived from medical record
measure: All-cause mortality
time frame: Baseline and through day 60
description: Noted in participant medical record
measure: Percentage of adverse events (AEs)
time frame: Baseline through day 14 or at discharge <day 14, at day 28, day 45 and day 60
description: CTCAE v5.0
measure: Percentage of serious adverse events (SAEs)
time frame: Baseline through day 14 or at discharge <day 14, at day 28, day 45 and day 60
description: CTCAE v5.0
measure: Proportion of participants with normalization of fever for 24 hours
time frame: Baseline through day 14 or at discharge <day 14
description: Standard daily temperature measurement and obtained from participant medical record
measure: Number of participants who develop new bacterial infection
time frame: Continuous throughout hospitalization up to 14 days
description: Noted in participant medical record
measure: Number of participants who develop new fungal infection
time frame: Continuous throughout hospitalization up to 14 days
description: Noted in participant medical record
measure: Incidence of Adult Respiratory distress Syndrome (ARDS2)
time frame: From day 1 though day 14 or at discharge <day 14
description: Noted in participant medical record
measure: Change in serum cytokine Interleukin (IL)-6
time frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14)
description: Serum collected from blood and assayed on Luminex panel performed by University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core
measure: Change in serum cytokine IL-8
time frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14)
description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
measure: Change in serum cytokines IL-1β
time frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14)
description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
measure: Change in serum cytokine Tumor Necrosis Factor (TNF-α)
time frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14)
description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
arm group label: ATI-450
arm group type: Active Comparator
description: Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Treated with matched placebo, orally, twice daily for 14 days
intervention type: Drug
intervention name: ATI-450
description: 50 mg (as determined from Phase I study) per dose. (100 mg per day). Up to a maximum of 14 days while inpatient. Patients discharged home or transferred to the intensive care unit (ICU) will be discontinued off drug permanently.
arm group label: ATI-450
intervention type: Drug
intervention name: Placebo
description: Placebo pill will be taken twice daily preferably spaced 12 hours apart.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory Gan, MD, PhD
role: Principal Investigator
affiliation: The University of Kansas
last name: Deepika Polineni, MD, PhD
role: Principal Investigator
affiliation: The University of Kansas
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
submitted: March 29, 2023
returned: April 19, 2023