<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/NCT04501978</url>
  </required_header>
  <id_info>
    <org_study_id>014 / ACTIV-3</org_study_id>
    <nct_id>NCT04501978</nct_id>
  </id_info>
  <brief_title>ACTIV-3: Therapeutics for Inpatients With COVID-19</brief_title>
  <acronym>TICO</acronym>
  <official_title>A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kirby Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington D.C. Veterans Affairs Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>AIDS Clinical Trials Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>US Department of Veterans Affairs</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Prevention and Early Treatment of Acute Lung Injury</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cardiothoracic Surgical Trials Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vir Biotechnology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brii Biosciences Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Molecular Partners AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</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>
      This study looks at the safety and effectiveness of different drugs in treating COVID-19 in&#xD;
      people who have been hospitalized with the infection. Participants in the study will be&#xD;
      treated with either a study drug plus current standard of care (SOC), or with placebo plus&#xD;
      current SOC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a master protocol to evaluate the safety and efficacy of multiple investigational&#xD;
      agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly&#xD;
      enhancing viral control in order to limit disease progression.&#xD;
&#xD;
      The protocol is for a randomized, blinded, controlled platform study that allows&#xD;
      investigational drugs to be added and dropped during the course of the study. This allows for&#xD;
      efficient testing of new drugs against placebo and standard of care (SOC) treatment within&#xD;
      the same study. When more than one drug is being tested at the same time, participants will&#xD;
      be randomly allocated to treatments or placebo.&#xD;
&#xD;
      Randomization will be stratified by study site pharmacy and disease severity. There are 2&#xD;
      disease severity strata: Participants without organ failure (severity stratum 1); and&#xD;
      participants with organ failure (severity stratum 2).&#xD;
&#xD;
      An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses&#xD;
      and summarize safety and efficacy outcomes. For investigational drugs with minimal&#xD;
      pre-existing safety knowledge, the pace of enrollment with be initially restricted, and there&#xD;
      will be an early review of safety data by the DSMB. For the study of each agent, at the&#xD;
      outset of the trial, only participants in disease severity stratum 1 will be enrolled. This&#xD;
      will continue until approximately 300 participants are enrolled and followed for 5 days. The&#xD;
      exact number will vary according to the speed of enrollment and the timing of DSMB meetings.&#xD;
      Prior to expanding enrollment to also include patients in disease severity stratum 2, safety&#xD;
      will be evaluated and a pre-specified futility assessment by the DSMB will be carried out&#xD;
      using 2 ordinal outcomes assessed at Day 5.&#xD;
&#xD;
      Both ordinal outcomes are used to assess futility because it is currently unclear whether the&#xD;
      investigational agents under study will primarily influence non-pulmonary outcomes, for which&#xD;
      risk is increased with SARS-CoV-2 infection, in part, through mechanisms that may be&#xD;
      different from those that influence pulmonary outcomes.&#xD;
&#xD;
      For investigational agents passing this futility assessment, enrollment of participants will&#xD;
      be expanded, seamlessly and without any data unblinding, to include participants in disease&#xD;
      severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses&#xD;
      will be based on the primary endpoint of sustained recovery and will use pre-specified&#xD;
      guidelines to determine early evidence of benefit, harm or futility for the investigational&#xD;
      agent. Participants will be followed for 18 months following randomization.&#xD;
&#xD;
      The international trials within this protocol will be conducted in several hundred clinical&#xD;
      sites. Participating sites are affiliated with networks funded by the United States National&#xD;
      Institutes of Health (NIH) and the US Department of Veterans Affairs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 4, 2020</start_date>
  <completion_date type="Actual">July 14, 2023</completion_date>
  <primary_completion_date type="Actual">April 6, 2022</primary_completion_date>
  <phase>Phase 3</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time from randomization to sustained recovery</measure>
    <time_frame>Up to Day 90</time_frame>
    <description>Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>Thru Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of time to sustained recovery and mortality</measure>
    <time_frame>Thru Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days alive outside short-term acute care hospital</measure>
    <time_frame>Up to Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary ordinal outcome</measure>
    <time_frame>Days 1-7, 14 and 28</time_frame>
    <description>Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary+ ordinal outcome</measure>
    <time_frame>Days 1-7</time_frame>
    <description>Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of clinical organ failure</measure>
    <time_frame>Thru Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of death or serious clinical COVID-19 related events</measure>
    <time_frame>Thru Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of cardiovascular events and thromboembolic events</measure>
    <time_frame>Thru Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death</measure>
    <time_frame>Thru Days 5 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of infusion reactions</measure>
    <time_frame>Thru Day 0</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of SAEs or death</measure>
    <time_frame>Thru 18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SARS-CoV-2 neutralizing antibody levels</measure>
    <time_frame>Baseline to Days 1, 3, 5, 28 and 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in overall titers of antibodies</measure>
    <time_frame>Baseline to Days 1, 3, 5, 28 and 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in neutralizing antibody levels</measure>
    <time_frame>Baseline to Days 1, 3, 5, 28 and 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of home use of supplemental oxygen above pre-morbid oxygen use</measure>
    <time_frame>18 months</time_frame>
    <description>Measured as: Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14 day period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of no home use of supplemental oxygen above pre-morbid oxygen use</measure>
    <time_frame>14 days</time_frame>
    <description>Measured as: Alive at home for an uninterrupted 14 day period and no use of continuous supplemental oxygen at end of 14 day time period.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2753</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this study will be randomized to receive one of the ACTIV-3 drug treatments plus Standard of Care (SOC) or placebo plus SOC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo plus SOC</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo arm may be pooled across more than one experimental arm if multiple investigational drugs are available to be tested at the same time. If it is not possible to use matching placebo over more than one experimental arm, additional placebo arms will be included in the study</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LY3819253</intervention_name>
    <description>Participants are no longer being randomized to this intervention.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Commercially available 0.9% sodium chloride solution. Administered by IV infusion</description>
    <arm_group_label>Placebo plus SOC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Remdesivir</intervention_name>
    <description>Provided to all study participants as SOC unless contraindicated for an individual patient.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
    <arm_group_label>Placebo plus SOC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>VIR-7831</intervention_name>
    <description>Participants are no longer being randomized to this intervention.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BRII-196/BRII-198</intervention_name>
    <description>Participants are no longer being randomized to this intervention.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AZD7442</intervention_name>
    <description>Participants are no longer being randomized to this intervention.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
    <other_name>AZD8895 + AZD1061</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MP0420</intervention_name>
    <description>Participants are no longer being randomized to this intervention.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
    <other_name>ensovibep</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PF-07304814</intervention_name>
    <description>250 mg per day for 5 days. Administered as a constant rate intravenous infusion. Suspended: Participants are not currently being randomized to this intervention.</description>
    <arm_group_label>ACTIV-3 Drug plus SOC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Positive test for COVID-19 and progressive disease suggestive of ongoing COVID-19&#xD;
             infection.&#xD;
&#xD;
          -  Symptoms of COVID-19 for ≤ 12 days.&#xD;
&#xD;
          -  Require admission to hospital for acute medical care (not for purely public health or&#xD;
             quarantine purposes).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received plasma from a person who recovered from COVID-19 or who&#xD;
             have received neutralizing monoclonal antibodies at any time prior to hospitalization.&#xD;
&#xD;
          -  Patients not willing to abstain from participation in other COVID-19 treatment trials&#xD;
             until after Day 5 of the study. Co-enrollment in certain trials that compare&#xD;
             recommended Standard of Care treatments may be allowed, based on the opinion of the&#xD;
             study leadership team.&#xD;
&#xD;
          -  Any condition which, in the opinion of the responsible investigator, participation&#xD;
             would not be in the best interest of the participant or that could prevent, limit, or&#xD;
             confound the protocol-specified assessments.&#xD;
&#xD;
          -  Patients considered unable to participate in study procedures.&#xD;
&#xD;
          -  Women of child-bearing potential who are not already pregnant at study entry and who&#xD;
             are unwilling to acknowledge strong advice to abstain from sexual intercourse with men&#xD;
             or practice appropriate contraception through 18 months of the study.&#xD;
&#xD;
          -  Women of child-bearing potential who are unwilling to acknowledge the strong advice to&#xD;
             abstain from sexual intercourse with men or practice appropriate contraception through&#xD;
             5 weeks of the study (PF-07304814 investigational agent).&#xD;
&#xD;
          -  Pregnant women (PF-07304814 investigational agents).&#xD;
&#xD;
          -  Nursing mothers (PF-07304814 investigational agents).&#xD;
&#xD;
          -  Men who are unwilling to acknowledge the strong advice to abstain from sexual&#xD;
             intercourse with women of child-bearing potential or to use barrier contraception&#xD;
             through 18 months of the study.&#xD;
&#xD;
          -  Men who are unwilling to acknowledge the strong advice to abstain from sexual&#xD;
             intercourse with women of child-bearing potential or to use barrier contraception&#xD;
             through 5 weeks of the study (PF-07304814 investigational agent).&#xD;
&#xD;
          -  Presence at study enrollment of any of the following:&#xD;
&#xD;
               1. stroke&#xD;
&#xD;
               2. meningitis&#xD;
&#xD;
               3. encephalitis&#xD;
&#xD;
               4. myelitis&#xD;
&#xD;
               5. myocardial ischemia&#xD;
&#xD;
               6. myocarditis&#xD;
&#xD;
               7. pericarditis&#xD;
&#xD;
               8. symptomatic congestive heart failure&#xD;
&#xD;
               9. arterial or deep venous thrombosis or pulmonary embolism&#xD;
&#xD;
          -  Current or imminent requirement for any of the following:&#xD;
&#xD;
               1. invasive mechanical ventilation&#xD;
&#xD;
               2. ECMO (extracorporeal membrane oxygenation)&#xD;
&#xD;
               3. Mechanical circulatory support&#xD;
&#xD;
               4. vasopressor therapy&#xD;
&#xD;
               5. commencement of renal replacement therapy at this admission (i.e. not patients on&#xD;
                  chronic renal replacement therapy).&#xD;
&#xD;
          -  Participants with moderate to severe hepatic impairment (i.e. Child-Pugh class B or C)&#xD;
             or acute liver failure (PF-07304814 investigational agent).&#xD;
&#xD;
          -  Participants receiving any medications or substances that are strong inhibitors or&#xD;
             inducers of cytochrome P450 (CYP) 3A4 (PF-07304814 investigational agent).&#xD;
&#xD;
          -  Patients will be excluded if taking drugs which have a narrow therapeutic window that&#xD;
             are substrates of CYP3A4, including but not limited to: astemizole, cisapride,&#xD;
             cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus,&#xD;
             tacrolimus, and terfenadine (PF-07304814 investigational agent).&#xD;
&#xD;
          -  Patients with a history of deep vein thrombosis or pulmonary thrombotic embolism&#xD;
             (Prior to initial futility assessment of PF-07304814 investigational agent).&#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>Prof. Jens Lundgren</last_name>
    <role>Principal Investigator</role>
    <affiliation>INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Prof. James Neaton</last_name>
    <role>Study Chair</role>
    <affiliation>INSIGHT Statistical and Coordinating Centre, University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Arizona VA Healthcare System (Site 074-009), 3601 S. 6th Ave.</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velocity Chula Vista (Site 080-034), 752 Medical Center Ct., Ste. 304</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Regional Medical Center (Site 203-005), 2823 Fresno Street</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velocity San Diego (Site 080-035), 5565 Grossmont Center Drive, Building 2, Suite 1</name>
      <address>
        <city>La Mesa</city>
        <state>California</state>
        <zip>91942</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92357</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Long Beach Healthcare System (Site 074-026), 5901 East 7th Street (09/151-M2)</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keck Hospital of USC (Site 301-020), 1500 San Pablo Street</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Blvd.</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sacramento VA Medical Center (Site 074-023), 10535 Hospital Way</name>
      <address>
        <city>Mather</city>
        <state>California</state>
        <zip>95655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hoag Memorial Hospital Presbyterian (Site 080-026), One Hoag Drive</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palo Alto VAMC (Site 074-005), 3801 Miranda Avenue</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Davis Health (Site 203-004), 2315 Stockton Blvd.</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA San Diego Healthcare System (Site 074-016), 3350 La Jolla Village Drive</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco VAMC (Site 074-002), 4150 Clement St.</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center (Site 203-001), Moffitt-Long Hospital, 505 Parnassus Ave.</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Hospital &amp; Clinics (Site 203-003), 300 Pasteur Dr.</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Site 066-002), 1124 W. Carson Street, CDCRC Building</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Denver Public Health (Site 017-004), 660 Bannock St., MC2600 (Infectious Disease Clinic)</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health / St. Joseph Hospital (Site 204-003), 1400 Jackson Street</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Haven VA Medical Center (Site 025-007), 950 Campbell Avenue</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital (Site 067-001), 3800 Reservoir Road NW</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Health Research Institute (Site 009-021), MedStar Washington Hospital Center, 110 Irving St., NW.</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington DC VA Medical Center (Site 009-004), 50 Irving Street NW</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Pines VAMC (Site 074-004), 10000 Bay Pines Blvd., Bldg. 100, Room 5B-104</name>
      <address>
        <city>Bay Pines</city>
        <state>Florida</state>
        <zip>33744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baycare Health System (Site 301-025), Morton Plant Hospital, 300 Pinellas Street</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Florida/South Georgia Veterans Health System (Site 074-011), 1601 SW. Archer Road</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608-1197</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Healthcare System (Site 648-002), Memorial Regional Hospital, 3501 Johnson Street</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami VAMC (Site 074-003), 1201 NW 16 Street</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillsborough County Health Department, University of South Florida (Site 032-001)</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University (Site 301-008), The Emory Clinic, Bldg. A, Suite 2236, 1365 Clifton Rd., NE</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lutheran Medical Group (Site 301-010), 7916 W. Jefferson Boulevard</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cotton O'Neil Clinical Research Center (Site 080-030), Stormont Vail Health, 1500 SW 10th Avenue</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky Hospital (Site 210-004), 1000 South Limestone St.</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation (Site 301-015), 1514 Jefferson Highway</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center (Site 301-019), 22 South Greene Street</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital (Site 202-002), 55 Fruit Street</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center (Site 202-001), 330 Brookline Ave.</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baystate Medical Center (Site 201-001), 759 Chestnut Street</name>
      <address>
        <city>Springfield</city>
        <state>Massachusetts</state>
        <zip>01199</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan (Site 205-001), 1500 East Medical Center Drive</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System, Henry Ford Hospital (Site 014-001), 2799 W. Grand Blvd.</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis Heart Institute Foundation (Site 301-026), Abbott Northwestern Hospital, 920 E 28th St. #100</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hennepin Healthcare (Site 027-001), 701 Park Avenue</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis VA Health Care System (Site 105-001), 1 Veterans Drive, Bldg 70</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55417</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M Health Fairview University of Minnesota Medical Center (Site 112-001), 500 Harvard St. SE.</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center (Site 202-005), 2500 North State Street</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA St. Louis Healthcare System (Site 074-027), 915 North Grand Blvd., Rm. C201</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center/Mary Hitchcock Memorial Hospital (Site 301-024), One Medical Center Drive</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cooper University Hospital (Site 019-001), One Cooper Plaza</name>
      <address>
        <city>Camden</city>
        <state>New Jersey</state>
        <zip>08103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lincoln Medical Center (New York Health and Hospitals/Lincoln) (Site 003-016), 234 E. 149th Street</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center Weiler Hospital (Site 206-003), 1825 Eastchester Road</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center Moses Hospital (Site 206-001), 111 E. 210th Street</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SUNY Downstate Medical Center (Site 033-001), 450 Clarkson Ave.</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maimonides Medical Center (Site 033-002), 4802 10th Avenue</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ichan School of Medicine at Mount Sinai (Site 301-012), One Gustave L. Levy Place, Box 1620</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Hospital (Site 301-006), 2301 Erwin Road</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences (Site 210-001), Medical Center Blvd</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center (Site 207-003), 234 Goodman Ave.</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center (Site 108-001), 11100 Euclid Avenue</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Avenue</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Avenue</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Marymount Hospital (Site 207-006), 12300 McCraken Road</name>
      <address>
        <city>Garfield Heights</city>
        <state>Ohio</state>
        <zip>44125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239-3098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Portland VA Healthcare System (Site 074-024), 3710 SW. US Veterans Hospital Road</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Magee-Womens Hospital (Site 209-003), 300 Halket Street</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Presbyterian Hospital (Site 209-001), 200 Lothrop Street</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Shadyside Hospital (Site 209-005), 5230 Centre Avenue</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital (Site 080-036), 593 Eddy Street</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Miriam Hospital (Site 080-039), 164 Summit Ave.</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02906</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Providence Healthcare System (Site 074-025), 830 Chalkstone Ave.</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ralph H. Johnson VA Medical Center (Site 074-015), 109 Bee Street</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MUSC Research Nexus Clinic (Site 210-002), 96 Jonathan Lucas St., CSB 214</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MUSC Health Florence Medical Center (Site 210-006), 805 Pamplico Highway</name>
      <address>
        <city>Florence</city>
        <state>South Carolina</state>
        <zip>29505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA TVHS Nashville Campus (Site 074-022), 1310 24th Avenue South</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hendrick Medical Center (Site 080-014), 1900 Pine Street</name>
      <address>
        <city>Abilene</city>
        <state>Texas</state>
        <zip>79601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRISTUS Spohn Shoreline Hospital (Site 080-001), 600 Elizabeth Street</name>
      <address>
        <city>Corpus Christi</city>
        <state>Texas</state>
        <zip>78404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkland Health and Hospital Systems (Site 084-002), 5200 Harry Hines Blvd</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center (Site 084-001), 1936 Amelia Court, 2nd Floor</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hermann Hospital (Site 203-006), 6411 Fannin Street</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michael E. DeBakey Veterans Affairs Medical Center (MEDV AMC) (Site 074-006), 2002 Holcombe Blvd.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRISTUS Good Shepherd Medical Center (Site 080-031), 700 E. Marshall Ave.</name>
      <address>
        <city>Longview</city>
        <state>Texas</state>
        <zip>75601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Hospital (Site 211-002), 419 Wakara Way, Suite 207</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LDS Hospital (Site 211-004), 8th Ave. C Street</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Health Systems (Site 301-021), 1215 Lee Street</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University Health System (Site 210-005), 1250 East Marshall Street</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carilion Roanoke Memorial Hospital (Site 080-018), 1906 Belleview Avenue</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salem VA Medical Center (Site 074-014), 1970 Roanoke Blvd.</name>
      <address>
        <city>Salem</city>
        <state>Virginia</state>
        <zip>24153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harborview Medical Center (Site 208-001), 325 9th Avenue</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Hospital First Hill (Site 208-005), 747 Broadway</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center - Montlake (Site 208-006), 1959 NE Pacific Street</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University (Site 301-023), One Medical Center Drive</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aalborg Hospital (Site 625-005), Hobrovej 18</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aarhus Universitetshospital, Skejby (Site 625-002), Department of Infectious Diseases, Palle Juul-Hensens Boulevard 99</name>
      <address>
        <city>Aarhus N</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Righospitalet (Site 625-006), Blegdamsvej 9,</name>
      <address>
        <city>Copenhagen Ø</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bispebjerg Hospital (Site 625-013), Bispebjerg Bakke 23</name>
      <address>
        <city>Copenhagen</city>
        <zip>2400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herlev/Gentofte Hospital (Site 625-012), Medicinsk Afdeling, Herlev Ringvej 75</name>
      <address>
        <city>Herlev</city>
        <zip>2730</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nordsjællands Hospital (Site 625-009), Dyrehavevej 29</name>
      <address>
        <city>Hillerød</city>
        <zip>3400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hvidovre University Hospital, Department of Infectious Diseases (Site 625-001), Kettegård allé 30</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kolding Sygehus (Site 625-011), Medicinsk Afdeling, Sygehusvej 24</name>
      <address>
        <city>Kolding</city>
        <zip>6000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense University Hospital (Site 625-004), Infektionsmedicinsk Forskningsenhed, J.B. Winsløwsgade 4</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zealand University Hospital, Roskilde (Site 625-010), Sygehusvej 10</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Democritus University of Thrace (Site 635-021), University General Hospital of Alexandroupolis, Dragana</name>
      <address>
        <city>Alexandroupolis</city>
        <state>Evros</state>
        <zip>68131</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Evangelismos COVID-19 Unit, (Site 635-020), 1st Dept. of Pulmonary and Critical Care Medicine, Evangelismos General Hospital, Dept., Ipsilantou 45-47</name>
      <address>
        <city>Athens</city>
        <zip>106 76</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1st Respiratory Medicine Dept., Athens University Medical School (Site 635-015), Athens Hospital for Diseases of the Chest &quot;Sotiria Hospital&quot;, 152 Mesogeion Ave.</name>
      <address>
        <city>Athens</city>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>3rd Dept. of Medicine, Medical School, NKUA (Site 635-022), Sotiria General Hospital, 152 Mesogeion Ave.</name>
      <address>
        <city>Athens</city>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Attikon University General Hospital (Site 635-009), 4th Dept. of Internal Medicine, Medical School, National and Kapodistrian University of Athens, 1 Rimini St., Haidari</name>
      <address>
        <city>Athens</city>
        <zip>124 62</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Human Virology Nigeria (IHVN) (Site 612-601), Plot 252, Herbert Macaulay Way, Central Business District</name>
      <address>
        <city>Abuja</city>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewódzki Szpital Zakazny (Site 625-302), Wolska 37</name>
      <address>
        <city>Warsaw</city>
        <zip>01-201</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tan Tock Seng Hospital (Site 612-201), National Centre for Infectious Diseases (NCID), 11 Jalan Tan Tock Seng</name>
      <address>
        <city>Singapore</city>
        <zip>308433</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol (Site 626-003), Infectious Disease Unit, Second Floor, Building Maternal, Road Canyet s/n</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova (Site 626-035), Av. Alcalde Rovira Roure 80</name>
      <address>
        <city>Lleida</city>
        <state>Leida</state>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Del Mar (Site 626-025), Paseo Maritimo 25-29</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron (Site 626-033), Passeig de la Vall d'Hebron 119-129</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic de Barcelona (Site 626-004), Carrer de Villaroel 170</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Bellvitge (Site 626-034), Carrer de la Feixa Llarga, s/n</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón (Site 626-001), Dr. Esquerdo, 46</name>
      <address>
        <city>Madrid</city>
        <zip>28017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos (Site 626-017), Enfermedades infecciosas, C/Martin Lagos CN</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCICEC (Clinical Trial Unit) Hospital Universitario La Paz (Site 626-012), Paseo de la Castellana 261, 2a planta Hospital Maternal</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Zurich (Site 621-201), Department of Infectious Diseases and Hospital Epidemiology, Raemistrasse 100</name>
      <address>
        <city>Zürich</city>
        <state>Zurich</state>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MRC/UVRI and LSHTM Uganda Research Unit (Site 634-601), Entebbe Regional Referral Hospital</name>
      <address>
        <city>Entebbe</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gulu Regional Referral Hospital (Site 634-603), Laroo Division, PO Box 160</name>
      <address>
        <city>Gulu</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Makerere University Lung Institute (Site 634-604), New Mulago Hospital Complex, Mulago Hill</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Hospital, Nsambya (Site 634-607), Nsambya Road Nsambya Hill, P.O. Box 7146</name>
      <address>
        <city>Kampala</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lira Regional Referral Hospital (Site 634-605)</name>
      <address>
        <city>Lira</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Masaka Regional Referral Hospital (Site 634-606), MRC/UVRI and LSHTM Uganda Research Unit, Plot 6 Circle Road, PO Box 556</name>
      <address>
        <city>Masaka</city>
        <country>Uganda</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Infirmary (Site 634-007), Queen Victoria Road</name>
      <address>
        <city>Newcastle Upon Tyne</city>
        <state>Northumbria</state>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital (Site 634-006), Pond Street, Hampstead</name>
      <address>
        <city>London</city>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and St. Thomas' NHS Foundation Trust (Site 634-011)</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Greece</country>
    <country>Nigeria</country>
    <country>Poland</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>Uganda</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Argentina</country>
    <country>Georgia</country>
    <country>India</country>
    <country>Mexico</country>
    <country>Mozambique</country>
    <country>Ukraine</country>
  </removed_countries>
  <link>
    <url>http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm</url>
    <description>FDA Safety Alerts and Recalls</description>
  </link>
  <link>
    <url>https://www.cdc.gov/coronavirus/2019-nCoV/index.html</url>
    <description>CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/clinical-trials/participant-guide</url>
    <description>A Participant's Guide to Clinical Trials (NIAID)</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/clinical-trials/find-a-clinical-trial</url>
    <description>Find a Clinical Trial (NIAID)</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/clinical-trials</url>
    <description>Clinical Trials at NIAID</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/</url>
    <description>National Institute for Allergy and Infectious Diseases (NIAID)</description>
  </link>
  <link>
    <url>https://www.covid19treatmentguidelines.nih.gov/</url>
    <description>NIH COVID-19 treatment guidelines</description>
  </link>
  <link>
    <url>https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management</url>
    <description>WHO COVID-19 treatment guidelines</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>August 23, 2023</last_update_submitted>
  <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>COVID 19</keyword>
  <keyword>Coronaviridae Infections</keyword>
  <keyword>Coronavirus Infections</keyword>
  <keyword>RNA Virus Infections</keyword>
  <keyword>Virus Diseases</keyword>
  <keyword>Nidovirales Infections</keyword>
  <keyword>SARS-CoV-2</keyword>
  <keyword>SARS Coronavirus</keyword>
  <keyword>ACTIV-3</keyword>
  <keyword>ACTIV3</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Remdesivir</mesh_term>
    <mesh_term>Cilgavimab and tixagevimab drug combination</mesh_term>
    <mesh_term>Bamlanivimab</mesh_term>
    <mesh_term>Sotrovimab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 5, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/78/NCT04501978/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04501978
org study id: 014 / ACTIV-3
nct id: NCT04501978
lead sponsor: 
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has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study looks at the safety and effectiveness of different drugs in treating COVID-19 in
      people who have been hospitalized with the infection. Participants in the study will be
      treated with either a study drug plus current standard of care (SOC), or with placebo plus
      current SOC.
This is a master protocol to evaluate the safety and efficacy of multiple investigational
      agents aimed at modifying the host immune response to SARS-CoV-2 infection, or directly
      enhancing viral control in order to limit disease progression.

      The protocol is for a randomized, blinded, controlled platform study that allows
      investigational drugs to be added and dropped during the course of the study. This allows for
      efficient testing of new drugs against placebo and standard of care (SOC) treatment within
      the same study. When more than one drug is being tested at the same time, participants will
      be randomly allocated to treatments or placebo.

      Randomization will be stratified by study site pharmacy and disease severity. There are 2
      disease severity strata: Participants without organ failure (severity stratum 1); and
      participants with organ failure (severity stratum 2).

      An independent Data and Safety Monitoring Board (DSMB) will regularly review interim analyses
      and summarize safety and efficacy outcomes. For investigational drugs with minimal
      pre-existing safety knowledge, the pace of enrollment with be initially restricted, and there
      will be an early review of safety data by the DSMB. For the study of each agent, at the
      outset of the trial, only participants in disease severity stratum 1 will be enrolled. This
      will continue until approximately 300 participants are enrolled and followed for 5 days. The
      exact number will vary according to the speed of enrollment and the timing of DSMB meetings.
      Prior to expanding enrollment to also include patients in disease severity stratum 2, safety
      will be evaluated and a pre-specified futility assessment by the DSMB will be carried out
      using 2 ordinal outcomes assessed at Day 5.

      Both ordinal outcomes are used to assess futility because it is currently unclear whether the
      investigational agents under study will primarily influence non-pulmonary outcomes, for which
      risk is increased with SARS-CoV-2 infection, in part, through mechanisms that may be
      different from those that influence pulmonary outcomes.

      For investigational agents passing this futility assessment, enrollment of participants will
      be expanded, seamlessly and without any data unblinding, to include participants in disease
      severity stratum 2 as well as those in disease severity stratum 1. Future interim analyses
      will be based on the primary endpoint of sustained recovery and will use pre-specified
      guidelines to determine early evidence of benefit, harm or futility for the investigational
      agent. Participants will be followed for 18 months following randomization.

      The international trials within this protocol will be conducted in several hundred clinical
      sites. Participating sites are affiliated with networks funded by the United States National
      Institutes of Health (NIH) and the US Department of Veterans Affairs.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time from randomization to sustained recovery
time frame: Up to Day 90
description: Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
measure: All-cause mortality
time frame: Thru Day 90
measure: Composite of time to sustained recovery and mortality
time frame: Thru Day 90
measure: Days alive outside short-term acute care hospital
time frame: Up to Day 90
measure: Pulmonary ordinal outcome
time frame: Days 1-7, 14 and 28
description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
measure: Pulmonary+ ordinal outcome
time frame: Days 1-7
description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
measure: Incidence of clinical organ failure
time frame: Thru Day 28
measure: Composite of death or serious clinical COVID-19 related events
time frame: Thru Day 90
measure: Composite of cardiovascular events and thromboembolic events
time frame: Thru Day 90
measure: Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death
time frame: Thru Days 5 and 28
measure: Incidence of infusion reactions
time frame: Thru Day 0
measure: Composite of SAEs or death
time frame: Thru 18 months
measure: Change in SARS-CoV-2 neutralizing antibody levels
time frame: Baseline to Days 1, 3, 5, 28 and 90
measure: Change in overall titers of antibodies
time frame: Baseline to Days 1, 3, 5, 28 and 90
measure: Change in neutralizing antibody levels
time frame: Baseline to Days 1, 3, 5, 28 and 90
measure: Incidence of home use of supplemental oxygen above pre-morbid oxygen use
time frame: 18 months
description: Measured as: Alive at home and no use of continuous supplemental oxygen for an uninterrupted 14 day period
measure: Incidence of no home use of supplemental oxygen above pre-morbid oxygen use
time frame: 14 days
description: Measured as: Alive at home for an uninterrupted 14 day period and no use of continuous supplemental oxygen at end of 14 day time period.
arm group label: ACTIV-3 Drug plus SOC
arm group type: Experimental
description: Participants in this study will be randomized to receive one of the ACTIV-3 drug treatments plus Standard of Care (SOC) or placebo plus SOC
arm group label: Placebo plus SOC
arm group type: Placebo Comparator
description: The placebo arm may be pooled across more than one experimental arm if multiple investigational drugs are available to be tested at the same time. If it is not possible to use matching placebo over more than one experimental arm, additional placebo arms will be included in the study
intervention type: Biological
intervention name: LY3819253
description: Participants are no longer being randomized to this intervention.
arm group label: ACTIV-3 Drug plus SOC
intervention type: Drug
intervention name: Placebo
description: Commercially available 0.9% sodium chloride solution. Administered by IV infusion
arm group label: Placebo plus SOC
intervention type: Biological
intervention name: Remdesivir
description: Provided to all study participants as SOC unless contraindicated for an individual patient.
arm group label: ACTIV-3 Drug plus SOC
arm group label: Placebo plus SOC
intervention type: Biological
intervention name: VIR-7831
description: Participants are no longer being randomized to this intervention.
arm group label: ACTIV-3 Drug plus SOC
intervention type: Biological
intervention name: BRII-196/BRII-198
description: Participants are no longer being randomized to this intervention.
arm group label: ACTIV-3 Drug plus SOC
intervention type: Biological
intervention name: AZD7442
description: Participants are no longer being randomized to this intervention.
arm group label: ACTIV-3 Drug plus SOC
other name: AZD8895 + AZD1061
intervention type: Drug
intervention name: MP0420
description: Participants are no longer being randomized to this intervention.
arm group label: ACTIV-3 Drug plus SOC
other name: ensovibep
intervention type: Drug
intervention name: PF-07304814
description: 250 mg per day for 5 days. Administered as a constant rate intravenous infusion. Suspended: Participants are not currently being randomized to this intervention.
arm group label: ACTIV-3 Drug plus SOC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Prof. Jens Lundgren
role: Principal Investigator
affiliation: INSIGHT Copenhagen International Coordinating Centre, Rigshospitalet, University of Copenhagen
last name: Prof. James Neaton
role: Study Chair
affiliation: INSIGHT Statistical and Coordinating Centre, University of Minnesota
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country: Denmark
country: Greece
country: Nigeria
country: Poland
country: Singapore
country: Spain
country: Switzerland
country: Uganda
country: United Kingdom
country: United States
country: Argentina
country: Georgia
country: India
country: Mexico
country: Mozambique
country: Ukraine
url: http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
description: FDA Safety Alerts and Recalls
url: https://www.cdc.gov/coronavirus/2019-nCoV/index.html
description: CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
url: https://www.niaid.nih.gov/clinical-trials/participant-guide
description: A Participant's Guide to Clinical Trials (NIAID)
url: https://www.niaid.nih.gov/clinical-trials/find-a-clinical-trial
description: Find a Clinical Trial (NIAID)
url: https://www.niaid.nih.gov/clinical-trials
description: Clinical Trials at NIAID
url: https://www.niaid.nih.gov/
description: National Institute for Allergy and Infectious Diseases (NIAID)
url: https://www.covid19treatmentguidelines.nih.gov/
description: NIH COVID-19 treatment guidelines
url: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/patient-management
description: WHO COVID-19 treatment guidelines
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Remdesivir
mesh term: Cilgavimab and tixagevimab drug combination
mesh term: Bamlanivimab
mesh term: Sotrovimab
sharing ipd: Undecided
provided document: 