<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/NCT04458298</url>
  </required_header>
  <id_info>
    <org_study_id>OP-101-004</org_study_id>
    <nct_id>NCT04458298</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate OP-101 (Dendrimer N-acetyl-cysteine) in Severe Coronavirus Disease 2019 (COVID-19) Patients</brief_title>
  <acronym>PRANA</acronym>
  <official_title>A Two-Stage, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OP-101 (Dendrimer N-acetyl-cysteine) in Patients With Severe COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ashvattha Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ashvattha Therapeutics, Inc.</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>
      The primary purpose of Stage-I of this study is to evaluate the safety and tolerability of&#xD;
      OP-101 in patients with severe COVID-19 and of Stage 2 of this study is to evaluate the&#xD;
      efficacy of OP-101 in patients with severe COVID-19.&#xD;
&#xD;
      The secondary purpose of Stage 1 and Stage 2 of this study is to determine the effect of&#xD;
      OP-101 reducing proinflammatory cytokines biomarkers in severe COVID-19 Patients.&#xD;
&#xD;
      A further secondary objective of Stage 2 of this study is:&#xD;
&#xD;
      To evaluate the safety and tolerability of OP-101 in patients with severe COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">August 11, 2020</start_date>
  <completion_date type="Actual">August 12, 2022</completion_date>
  <primary_completion_date type="Actual">August 12, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stage I: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0</measure>
    <time_frame>Up to Day 60</time_frame>
    <description>Number of participants with treatment emergent adverse events will be evaluated as a measure of safety and tolerability of OP-101 by monitoring and documenting all adverse events, which include laboratory test variables.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stage II: Percentage of Participants Who Were Alive (i.e., not died due to any reason) at Day 29</measure>
    <time_frame>Day 29</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stage I: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS)</measure>
    <time_frame>Up to Day 30</time_frame>
    <description>WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Time to Resolution of Fever for at least 48 hours Without Antipyretics for Patients with Documented Fever (&gt;=37.2 degree celsius [oral], or &gt;=37.8 degree celsius [rectal], or &gt;=38.0 degree celsius [tympanic])</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Time to Improvement in Oxygenation for at least 48 hours</measure>
    <time_frame>Up to Day 30</time_frame>
    <description>Improvement in oxygenation is defined by increase in pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) of &gt;=50 compared with nadir SpO2/FiO2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale</measure>
    <time_frame>Baseline up to Day 30</time_frame>
    <description>WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of &lt;=2 and maintained for 24 hours</measure>
    <time_frame>Up to Day 30</time_frame>
    <description>NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Percentage of Patients Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 30</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Days of Resting Respiratory Rate of more than 24 breath/min</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Days with Hypoxemia</measure>
    <time_frame>Up to Day 30</time_frame>
    <description>Hypoxemia is defined by Saturation of Peripheral Oxygen (SpO2) of less than (&lt;) 95 percent (%) on room air or acute respiratory distress syndrome (ARDS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Days of Supplemental Oxygen use</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Ventilator-free Days</measure>
    <time_frame>Up to Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Days in Intensive Care Unit (ICU)</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Days of Hospitalization for Survivors</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Number of Participants with all cause Deaths</measure>
    <time_frame>Up to Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Percent Change from Baseline in Proinflammatory Cytokines</measure>
    <time_frame>Baseline up to Day 30</time_frame>
    <description>Percent change from baseline in proinflammatory cytokines (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage I: Incidence of Drug-related Serious Adverse Events (SAEs)</measure>
    <time_frame>Up to Day 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Participants Who Were Alive and free of Respiratory Failure</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Respiratory failure is defined as at least 1 of the following: i. Endotracheal intubation and mechanical ventilation; ii. Oxygen delivered by high-flow nasal cannula (&gt;20 L/minute; &gt;=50% oxygen) OR fraction of inspired oxygen &gt;50% delivered by Face Mask, Venturi, Rebreather Mask, Oxymizer Mask; iii. Non-invasive positive pressure oxygen - Continuous Positive Airway Pressure (CPAP) use for chronic sleep apnea treatment is not included in the definition of respiratory failure; iv. Extracorporeal membrane oxygenation (ECMO).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Participants Alive and Free of Invasive Mechanical Ventilation</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Participants Alive and Discharged From the Hospital</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percentage of Participants Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 29</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Percent Change from Baseline in Proinflammatory Biomarkers</measure>
    <time_frame>Baseline up to Day 29</time_frame>
    <description>Percent change from baseline in proinflammatory cytokines (CRP, ferritin, IL-6, and serum neurofilament light chain [sNfL]) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stage II: Number of Days in Intensive Care Unit (ICU)</measure>
    <time_frame>Up to Day 29</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Stage I: Cohort A: OP-101 2 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single intravenous (IV) infusion of OP-101 2 milligram per kilogram (mg/kg) on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: Cohort B: OP-101 4 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of OP-101 4 mg/kg on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: Cohort C: OP-101 8 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of OP-101 8 mg/kg on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I: Cohort D: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive a single IV infusion of matching placebo on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II: Cohort E: OP-101 8 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single IV infusion of OP-101 8 mg/kg on Days 1 and 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II: Cohort F: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive a single IV infusion of matching placebo on Days 1 and 4.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OP-101</intervention_name>
    <description>OP-101 infusion will be administered intravenously.</description>
    <arm_group_label>Stage I: Cohort A: OP-101 2 mg/kg</arm_group_label>
    <arm_group_label>Stage I: Cohort B: OP-101 4 mg/kg</arm_group_label>
    <arm_group_label>Stage I: Cohort C: OP-101 8 mg/kg</arm_group_label>
    <arm_group_label>Stage II: Cohort E: OP-101 8 mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo infusion will be administered intravenously.</description>
    <arm_group_label>Stage I: Cohort D: Placebo</arm_group_label>
    <arm_group_label>Stage II: Cohort F: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Stage I:&#xD;
&#xD;
          -  Body mass index (BMI) less than or equal to (&lt;=) 35 kilogram per meter square (kg/m^2)&#xD;
&#xD;
          -  Positive laboratory test for severe acute respiratory syndrome coronavirus 2&#xD;
             (SARS-CoV-2) or respiratory infection with recent exposure to a person with&#xD;
             laboratory-proven SARS-CoV-2&#xD;
&#xD;
          -  Patient has an ordinal scale score between 5 and 7, inclusive, using the WHO 7OS&#xD;
&#xD;
          -  Hypoxemia defined by saturation of peripheral oxygen (SpO2) of less than (&lt;) 95&#xD;
             percent (%) on room air or Acute respiratory distress syndrome (ARDS)&#xD;
&#xD;
          -  Occurrence of at least two of the following criteria: fever greater than (&gt;) 38.0&#xD;
             degree celsius, tachycardia &gt;90 beats/minute, tachypnea &gt;20 breaths/minute,&#xD;
             leucocytosis &gt;12*109 per liter (/L) or leucopoenia &lt;4 *10^9/L&#xD;
&#xD;
          -  Enrollment must occur within 72 hours from the initiation of mechanical ventilation or&#xD;
             high-flow oxygen&#xD;
&#xD;
          -  A signed informed consent form (ICF) from the patient or the patient's legally&#xD;
             authorized representative must be available (telephone consent is acceptable)&#xD;
&#xD;
          -  Female patients may not be pregnant, lactating, or breastfeeding&#xD;
&#xD;
          -  Female patients of childbearing potential must have negative result for pregnancy test&#xD;
             at screening&#xD;
&#xD;
          -  Male patients must agree to use a barrier method of contraception during the study and&#xD;
             for 90 days after the last dose&#xD;
&#xD;
          -  Participants must have an estimated glomerular filtration rate of greater than or&#xD;
             equal to (&gt;=) 45 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) at&#xD;
             screening&#xD;
&#xD;
          -  Must agree not to enroll in another study of an investigational agent prior to&#xD;
             completion of this study.&#xD;
&#xD;
        Stage II:&#xD;
&#xD;
          -  Positive laboratory test for SARS-CoV-2 or respiratory infection with recent exposure&#xD;
             to a person with laboratory-proven SARS-CoV-2&#xD;
&#xD;
          -  Patient has an ordinal scale score between 5 and 8, inclusive, using the WHO 10OS.&#xD;
&#xD;
          -  Patients with an ordinal score of 5 must be receiving oxygen by mask at a rate of 10 L&#xD;
             or greater&#xD;
&#xD;
          -  Hypoxemia defined by SpO2 of &lt;95% on room air or diagnosed with ARDS&#xD;
&#xD;
          -  Hyperinflammation (elevated CRP &gt; upper limit of local normal for laboratory range) at&#xD;
             screening&#xD;
&#xD;
          -  A signed ICF from the patient or the patient's legally authorized representative must&#xD;
             be available (telephone consent is acceptable)&#xD;
&#xD;
          -  Female patients may not be pregnant, lactating, or breastfeeding&#xD;
&#xD;
          -  Female patients of childbearing potential must have negative result for pregnancy test&#xD;
             at screening&#xD;
&#xD;
          -  Patients must have an estimated glomerular filtration rate of &gt;= 30 mL/min/1.73 m^2 at&#xD;
             screening&#xD;
&#xD;
          -  Male patients must agree to use a barrier method of contraception during the study and&#xD;
             for 90 days after the last dose&#xD;
&#xD;
          -  Must agree not to enroll in another study of an investigational agent prior to&#xD;
             completion of this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Stage I:&#xD;
&#xD;
          -  Not expected to survive for more than 24 hours&#xD;
&#xD;
          -  Underlying clinical condition where, in the opinion of the investigator, it would be&#xD;
             extremely unlikely that the patient would come off ventilation (eg, motor neuron&#xD;
             disease, Duchenne muscular dystrophy, or rapidly progressive interstitial pulmonary&#xD;
             fibrosis)&#xD;
&#xD;
          -  Severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy&#xD;
             or mechanical ventilation (noninvasive ventilation or via tracheotomy) except for&#xD;
             continuous positive airway pressure or bi-level positive airway pressure used solely&#xD;
             for sleep-disordered breathing&#xD;
&#xD;
          -  Congestive heart failure, defined as New York Heart Association Class IV&#xD;
&#xD;
          -  Acute left ventricular failure or myocardial infarction&#xD;
&#xD;
          -  Currently receiving extracorporeal membrane oxygenation (ECMO) therapy&#xD;
&#xD;
          -  Receiving renal dialysis therapy for chronic renal failure&#xD;
&#xD;
          -  Moderate to severe liver failure (Childs-Pugh Score &gt;12)&#xD;
&#xD;
          -  Presence of any active malignancy (other than nonmelanoma skin cancer) that required&#xD;
             treatment within the last 2 years&#xD;
&#xD;
          -  Lung transplant patient&#xD;
&#xD;
          -  WHO Class III or IV pulmonary hypertension&#xD;
&#xD;
          -  Documented deep venous thrombosis or pulmonary embolism within past 3 months&#xD;
&#xD;
          -  Major trauma in the preceding 5 days&#xD;
&#xD;
          -  Concurrent treatment with immune modulatory study drugs (e.g., anti-IL6 antibodies,&#xD;
             Janus kinase (JAK) kinase inhibitors) or other agents with actual or possible direct&#xD;
             acting antiviral activity against SARS-CoV-2 within 30 days or 5 half-lives, whichever&#xD;
             is longer, prior to dosing with OP-101; except for those that have received FDA&#xD;
             emergency-use authorization and have become standard of care (SOC). Concurrent&#xD;
             treatment with corticosteroids is permitted if participant has documented continued&#xD;
             hypoxemia (SpO2 of &lt;95% on room air) and hyper-inflammation (CRP&gt;=10 mg/L) at&#xD;
             screening.&#xD;
&#xD;
          -  Has lost or donated &gt;450 mL of whole blood or blood products within 30 days before&#xD;
             screening&#xD;
&#xD;
          -  Has any finding that, in the view of the investigator or medical monitor, would&#xD;
             compromise the patient's safety requirements&#xD;
&#xD;
          -  Is employed by the Sponsor, the contract research organization, or the study site&#xD;
             (permanent, temporary contract worker, or designee responsible for the conduct of the&#xD;
             study), or is a family member (spouse, parent, sibling, or child) of the Sponsor,&#xD;
             contract research organization, or study site employee.&#xD;
&#xD;
        Stage II:&#xD;
&#xD;
          -  Not expected to survive for more than 24 hours&#xD;
&#xD;
          -  Underlying clinical condition where, in the opinion of the investigator, it would be&#xD;
             extremely unlikely that the patient would come off ventilation (e.g., motor neuron&#xD;
             disease, Duchenne muscular dystrophy, or rapidly progressive interstitial pulmonary&#xD;
             fibrosis)&#xD;
&#xD;
          -  Severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy&#xD;
             or mechanical ventilation (noninvasive ventilation or via tracheotomy) except for&#xD;
             continuous positive airway pressure or bi-level positive airway pressure used solely&#xD;
             for sleep-disordered breathing&#xD;
&#xD;
          -  Congestive heart failure, defined as New York Heart Association Class IV&#xD;
&#xD;
          -  Acute left ventricular failure or myocardial infarction&#xD;
&#xD;
          -  Currently receiving ECMO therapy&#xD;
&#xD;
          -  Receiving renal dialysis therapy for end stage renal disease&#xD;
&#xD;
          -  Moderate to severe liver failure (Childs-Pugh Score &gt;12)&#xD;
&#xD;
          -  Presence of any active malignancy (other than nonmelanoma skin cancer) that required&#xD;
             treatment within the last 2 years&#xD;
&#xD;
          -  Lung transplant patient&#xD;
&#xD;
          -  WHO Class III or IV pulmonary hypertension&#xD;
&#xD;
          -  Documented deep venous thrombosis or pulmonary embolism within past 3 months&#xD;
&#xD;
          -  Major trauma in the preceding 5 days&#xD;
&#xD;
          -  Concurrent treatment with approved or emergency use authorized immune modulatory study&#xD;
             drugs (eg, anti-IL6 antibodies [tocilizumab], JAK kinase inhibitors [baricitinib]) or&#xD;
             other investigational agents with actual or possible direct acting antiviral activity&#xD;
             against SARS-CoV-2 within 30 days or 5 half-lives, whichever is longer, before dosing&#xD;
             with OP-101.&#xD;
&#xD;
          -  Has lost or donated &gt;450 mL of whole blood or blood products within 30 days before&#xD;
             screening&#xD;
&#xD;
          -  Mechanical ventilation for &gt;72 hours at the time of dosing&#xD;
&#xD;
          -  Has any finding that, in the view of the investigator or medical monitor, would&#xD;
             compromise the patient's safety requirements&#xD;
&#xD;
          -  Is employed by the Sponsor, the contract research organization, or the study site&#xD;
             (permanent, temporary contract worker, or designee responsible for the conduct of the&#xD;
             study), or is a family member (spouse, parent, sibling, or child) of the Sponsor,&#xD;
             contract research organization, or study site employee.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research site</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Amarillo</city>
        <state>Texas</state>
        <zip>79109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-COV-2</keyword>
  <keyword>Coronavirus</keyword>
  <keyword>Cytokine storm</keyword>
  <keyword>Acute respiratory distress syndrome</keyword>
  <keyword>Inflammation</keyword>
  <keyword>IL-6</keyword>
  <keyword>Treatment</keyword>
  <keyword>OP-101</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04458298
org study id: OP-101-004
nct id: NCT04458298
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary purpose of Stage-I of this study is to evaluate the safety and tolerability of
      OP-101 in patients with severe COVID-19 and of Stage 2 of this study is to evaluate the
      efficacy of OP-101 in patients with severe COVID-19.

      The secondary purpose of Stage 1 and Stage 2 of this study is to determine the effect of
      OP-101 reducing proinflammatory cytokines biomarkers in severe COVID-19 Patients.

      A further secondary objective of Stage 2 of this study is:

      To evaluate the safety and tolerability of OP-101 in patients with severe COVID-19.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Stage I: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0
time frame: Up to Day 60
description: Number of participants with treatment emergent adverse events will be evaluated as a measure of safety and tolerability of OP-101 by monitoring and documenting all adverse events, which include laboratory test variables.
measure: Stage II: Percentage of Participants Who Were Alive (i.e., not died due to any reason) at Day 29
time frame: Day 29
measure: Stage I: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS)
time frame: Up to Day 30
description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.
measure: Stage I: Time to Resolution of Fever for at least 48 hours Without Antipyretics for Patients with Documented Fever (>=37.2 degree celsius [oral], or >=37.8 degree celsius [rectal], or >=38.0 degree celsius [tympanic])
time frame: Up to Day 30
measure: Stage I: Time to Improvement in Oxygenation for at least 48 hours
time frame: Up to Day 30
description: Improvement in oxygenation is defined by increase in pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) of >=50 compared with nadir SpO2/FiO2.
measure: Stage I: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale
time frame: Baseline up to Day 30
description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.
measure: Stage I: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of <=2 and maintained for 24 hours
time frame: Up to Day 30
description: NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C).
measure: Stage I: Percentage of Patients Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 30
time frame: Up to Day 30
measure: Stage I: Number of Days of Resting Respiratory Rate of more than 24 breath/min
time frame: Up to Day 30
measure: Stage I: Number of Days with Hypoxemia
time frame: Up to Day 30
description: Hypoxemia is defined by Saturation of Peripheral Oxygen (SpO2) of less than (<) 95 percent (%) on room air or acute respiratory distress syndrome (ARDS).
measure: Stage I: Number of Days of Supplemental Oxygen use
time frame: Up to Day 30
measure: Stage I: Number of Ventilator-free Days
time frame: Up to Day 28
measure: Stage I: Number of Days in Intensive Care Unit (ICU)
time frame: Up to Day 30
measure: Stage I: Number of Days of Hospitalization for Survivors
time frame: Up to Day 30
measure: Stage I: Number of Participants with all cause Deaths
time frame: Up to Day 30
measure: Stage I: Percent Change from Baseline in Proinflammatory Cytokines
time frame: Baseline up to Day 30
description: Percent change from baseline in proinflammatory cytokines (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) will be reported.
measure: Stage I: Incidence of Drug-related Serious Adverse Events (SAEs)
time frame: Up to Day 60
measure: Stage II: Percentage of Participants Who Were Alive and free of Respiratory Failure
time frame: Up to Day 29
description: Respiratory failure is defined as at least 1 of the following: i. Endotracheal intubation and mechanical ventilation; ii. Oxygen delivered by high-flow nasal cannula (>20 L/minute; >=50% oxygen) OR fraction of inspired oxygen >50% delivered by Face Mask, Venturi, Rebreather Mask, Oxymizer Mask; iii. Non-invasive positive pressure oxygen - Continuous Positive Airway Pressure (CPAP) use for chronic sleep apnea treatment is not included in the definition of respiratory failure; iv. Extracorporeal membrane oxygenation (ECMO).
measure: Stage II: Percentage of Participants Alive and Free of Invasive Mechanical Ventilation
time frame: Up to Day 29
measure: Stage II: Percentage of Participants Alive and Discharged From the Hospital
time frame: Up to Day 29
measure: Stage II: Percentage of Participants Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 29
time frame: Up to Day 29
measure: Stage II: Percent Change from Baseline in Proinflammatory Biomarkers
time frame: Baseline up to Day 29
description: Percent change from baseline in proinflammatory cytokines (CRP, ferritin, IL-6, and serum neurofilament light chain [sNfL]) will be reported.
measure: Stage II: Number of Days in Intensive Care Unit (ICU)
time frame: Up to Day 29
arm group label: Stage I: Cohort A: OP-101 2 mg/kg
arm group type: Experimental
description: Participants will receive a single intravenous (IV) infusion of OP-101 2 milligram per kilogram (mg/kg) on Day 1.
arm group label: Stage I: Cohort B: OP-101 4 mg/kg
arm group type: Experimental
description: Participants will receive a single IV infusion of OP-101 4 mg/kg on Day 1.
arm group label: Stage I: Cohort C: OP-101 8 mg/kg
arm group type: Experimental
description: Participants will receive a single IV infusion of OP-101 8 mg/kg on Day 1.
arm group label: Stage I: Cohort D: Placebo
arm group type: Placebo Comparator
description: Participants will receive a single IV infusion of matching placebo on Day 1.
arm group label: Stage II: Cohort E: OP-101 8 mg/kg
arm group type: Experimental
description: Participants will receive a single IV infusion of OP-101 8 mg/kg on Days 1 and 4.
arm group label: Stage II: Cohort F: Placebo
arm group type: Placebo Comparator
description: Participants will receive a single IV infusion of matching placebo on Days 1 and 4.
intervention type: Drug
intervention name: OP-101
description: OP-101 infusion will be administered intravenously.
arm group label: Stage I: Cohort A: OP-101 2 mg/kg
arm group label: Stage I: Cohort B: OP-101 4 mg/kg
arm group label: Stage I: Cohort C: OP-101 8 mg/kg
arm group label: Stage II: Cohort E: OP-101 8 mg/kg
intervention type: Drug
intervention name: Placebo
description: Matching placebo infusion will be administered intravenously.
arm group label: Stage I: Cohort D: Placebo
arm group label: Stage II: Cohort F: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No