<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/NCT04456413</url>
  </required_header>
  <id_info>
    <org_study_id>Pro2020-0542</org_study_id>
    <nct_id>NCT04456413</nct_id>
  </id_info>
  <brief_title>Convalescent Plasma as Treatment for Subjects With Early COVID-19 Infection</brief_title>
  <official_title>Phase II Randomized Study of Convalescent Plasma From Recovered COVID-19 Donors Collected by Plasmapheresis as Treatment for Subjects With Early COVID-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hackensack Meridian Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Hackensack Meridian Health</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 is a phase II randomized study of convalescent plasma for the treatment of&#xD;
           non-immune individuals with COVID-19 infection at high risk of complications.&#xD;
&#xD;
        -  Subjects will be considered as having completed the study after 2 months (+/- 5) days,&#xD;
           unless consent withdrawal or death occurs first.&#xD;
&#xD;
        -  Subjects will be randomized to receiving convalescent plasma or best supportive care.&#xD;
&#xD;
        -  Patients randomized to best supportive care may receive plasma should they require&#xD;
           hospitalization for progression of COVID-19 disease.&#xD;
&#xD;
        -  The final analysis will be conducted once the last subject completes the 2-month visit&#xD;
           or withdraws from the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overall study design&#xD;
&#xD;
        -  This is a phase II randomized study of convalescent plasma for the treatment of&#xD;
           non-immune individuals with COVID-19 infection at high risk of complications.&#xD;
&#xD;
        -  Subjects will be considered as having completed the study after 2 months (+/- 5) days,&#xD;
           unless consent withdrawal or death occurs first.&#xD;
&#xD;
        -  Subjects will be randomized to receiving convalescent plasma or best supportive care.&#xD;
&#xD;
        -  Patients randomized to best supportive care may receive plasma should they require&#xD;
           hospitalization for progression of COVID-19 disease.&#xD;
&#xD;
        -  The final analysis will be conducted once the last subject completes the 2-month visit&#xD;
           or withdraws from the study.&#xD;
&#xD;
      A total of 306 subjects will be recruited, 153 for each arm. If a patient in the best&#xD;
      supportive care arm requires hospitalization, the patient will be eligible to receive&#xD;
      convalescent plasma if requested and/or deemed medically appropriate by the admitting&#xD;
      physician.&#xD;
&#xD;
      Overall study duration&#xD;
&#xD;
        -  The study begins when the first subject (donor or recipient) signs the informed consent.&#xD;
           The study will end once the last enrolled subject completes the study (likely a&#xD;
           recipient).&#xD;
&#xD;
        -  The expected duration of the study is approximately 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of accrual&#xD;
  </why_stopped>
  <start_date type="Actual">November 6, 2020</start_date>
  <completion_date type="Actual">May 4, 2021</completion_date>
  <primary_completion_date type="Actual">April 29, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hospitalization Rate</measure>
    <time_frame>10 Days</time_frame>
    <description>The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Symptoms Resolution</measure>
    <time_frame>2 Months</time_frame>
    <description>The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 Months</time_frame>
    <description>Overall survival (OS) will be defined as the time in days from study entry to death. Patients who are alive on the date of closing follow-up will be censored on that date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Virologic Clearance by Nasopharyngeal Swab at 2 and 4 Weeks</measure>
    <time_frame>2 and 4 Weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Nasopharyngeal Swab Positivity in Donors</measure>
    <time_frame>2 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Donor Titers Level</measure>
    <time_frame>2 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of Donor Titers Level on Efficacy</measure>
    <time_frame>2 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.</measure>
    <time_frame>Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma Product's Cytokine Level Assessment</measure>
    <time_frame>Day 0</time_frame>
    <description>Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data.</description>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's Mannose-binding Lectin (MBL) Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's Procalcitonin (PCT) Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's C-reactive Protein (CRP) Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's Annexin V Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's Surfactant Protein D (SP-D) Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's microRNA Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Product's Immunoglobulin Level Assessment</measure>
    <time_frame>Day 0</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization</measure>
    <time_frame>2 Weeks and 4 Weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization</measure>
    <time_frame>2 Weeks and 4 Weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Rates of Adverse Events Associated With Convalescent Plasma Infusion.</measure>
    <time_frame>Day 3 and 7, Weeks 2 and 4</time_frame>
    <description>Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Convalescent Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fresh or frozen plasma will be infused one time to patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Best Supportive Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Convalescent Plasma</intervention_name>
    <description>Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection</description>
    <arm_group_label>Convalescent Plasma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Best Supportive Care</intervention_name>
    <description>Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.</description>
    <arm_group_label>Best Supportive Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Donor Eligibility Criteria:&#xD;
&#xD;
          -  Age 18-60&#xD;
&#xD;
          -  A history of a positive nasopharyngeal swab for COVID-19 or a history of positive&#xD;
             antibody titer test.&#xD;
&#xD;
          -  At least 14 days from resolution of COVID-19-associated symptoms including fevers.&#xD;
&#xD;
          -  A negative nasopharyngeal swab (or similar test) for COVID-19&#xD;
&#xD;
          -  anti-SARS-CoV2 titers &gt;1:500&#xD;
&#xD;
          -  Adequate venous access for apheresis&#xD;
&#xD;
          -  Meets donor eligibility criteria in accordance to Hackensack University Medical Center&#xD;
             (HUMC) Collection Facility at the John Theurer Cancer Center (JTCC) if collecting at&#xD;
             the JTCC, and all regulatory agencies as describes in SOP 800 01.&#xD;
&#xD;
          -  Required testing of the donor and product must be performed in accordance to FDA&#xD;
             regulations (21 CFR 610.40), and the donation must be found suitable (21 CFR 630.30)&#xD;
&#xD;
        Recipient Eligibility Criteria:&#xD;
&#xD;
          -  Patient age &gt;30 years old, newly diagnosed with a COVID-19 infection with onset of&#xD;
             first symptoms &lt; 96 hours.&#xD;
&#xD;
          -  And least one other high-risk feature:&#xD;
&#xD;
               1. Age &gt; 65&#xD;
&#xD;
               2. BMI 30 or above&#xD;
&#xD;
               3. Hypertension, defined as SBP above 140 or DBP above 90, or requiring medication&#xD;
                  for control.&#xD;
&#xD;
               4. Coronary artery disease (history, not ECG changes only)&#xD;
&#xD;
               5. Congestive heart failure&#xD;
&#xD;
               6. Peripheral vascular disease (includes aortic aneurysm &gt;= 6 cm)&#xD;
&#xD;
               7. Cerebrovascular disease (history of CVA or TIA)&#xD;
&#xD;
               8. Dementia&#xD;
&#xD;
               9. Chronic pulmonary disease&#xD;
&#xD;
              10. Liver disease (such as portal hypertension, chronic hepatitis)&#xD;
&#xD;
              11. Diabetes (excludes diet-controlled alone)&#xD;
&#xD;
              12. Moderate or severe renal disease defined as having a GFR &lt; 60 mL/min&#xD;
&#xD;
              13. Cancer (exclude if &gt; 5 year in remission)&#xD;
&#xD;
              14. AIDS (not just HIV positive)&#xD;
&#xD;
        Recipient exclusion criteria:&#xD;
&#xD;
          -  History of severe transfusion reaction to plasma products&#xD;
&#xD;
          -  Need for oxygen supplementation&#xD;
&#xD;
          -  Positive test for COVID-19 antibodies&#xD;
&#xD;
          -  Chemotherapy-induced neutropenia (ANC &lt; 0.5 x 103/mcL)&#xD;
&#xD;
          -  Immunosuppressive medications except for prednisone (or steroid equivalent) &gt; 10 mg&#xD;
             daily.&#xD;
&#xD;
          -  Performance status &lt; 50 by KPS&#xD;
&#xD;
          -  Pneumonia by radiographic evaluation&#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>Michele L Donato, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hackensack Meridian Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <results_first_submitted>December 9, 2022</results_first_submitted>
  <results_first_submitted_qc>January 27, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">February 10, 2023</results_first_posted>
  <last_update_submitted>January 27, 2023</last_update_submitted>
  <last_update_submitted_qc>January 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Coronavirus</keyword>
  <keyword>Covid19</keyword>
  <keyword>SARS-CoV-2</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT04456413/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <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>February 17, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT04456413/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Convalescent Plasma</title>
          <description>Fresh or frozen plasma will be infused one time to patients&#xD;
Convalescent Plasma: Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection</description>
        </group>
        <group group_id="P2">
          <title>Best Supportive Care</title>
          <description>Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.&#xD;
Best Supportive Care: Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Convalescent Plasma</title>
          <description>Fresh or frozen plasma will be infused one time to patients&#xD;
Convalescent Plasma: Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection</description>
        </group>
        <group group_id="B2">
          <title>Best Supportive Care</title>
          <description>Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.&#xD;
Best Supportive Care: Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="21"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Hospitalization Rate</title>
        <description>The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.</description>
        <time_frame>10 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Convalescent Plasma</title>
            <description>Fresh or frozen plasma will be infused one time to patients&#xD;
Convalescent Plasma: Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection</description>
          </group>
          <group group_id="O2">
            <title>Best Supportive Care</title>
            <description>Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.&#xD;
Best Supportive Care: Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.</description>
          </group>
        </group_list>
        <measure>
          <title>Hospitalization Rate</title>
          <description>The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.</description>
          <units>Percentage of Patients Hospitalized</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0"/>
                    <measurement group_id="O2" value="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Symptoms Resolution</title>
        <description>The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.</description>
        <time_frame>2 Months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival (OS) will be defined as the time in days from study entry to death. Patients who are alive on the date of closing follow-up will be censored on that date.</description>
        <time_frame>2 Months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Virologic Clearance by Nasopharyngeal Swab at 2 and 4 Weeks</title>
        <time_frame>2 and 4 Weeks</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Nasopharyngeal Swab Positivity in Donors</title>
        <time_frame>2 Months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Donor Titers Level</title>
        <time_frame>2 Months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Impact of Donor Titers Level on Efficacy</title>
        <time_frame>2 Months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.</title>
        <time_frame>Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Cytokine Level Assessment</title>
        <description>Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data.</description>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Mannose-binding Lectin (MBL) Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Procalcitonin (PCT) Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's C-reactive Protein (CRP) Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Annexin V Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Surfactant Protein D (SP-D) Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's microRNA Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Product's Immunoglobulin Level Assessment</title>
        <time_frame>Day 0</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization</title>
        <time_frame>2 Weeks and 4 Weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization</title>
        <time_frame>2 Weeks and 4 Weeks</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Rates of Adverse Events Associated With Convalescent Plasma Infusion.</title>
        <description>Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days).</description>
        <time_frame>Day 3 and 7, Weeks 2 and 4</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Convalescent Plasma</title>
          <description>Fresh or frozen plasma will be infused one time to patients&#xD;
Convalescent Plasma: Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection</description>
        </group>
        <group group_id="E2">
          <title>Best Supportive Care</title>
          <description>Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.&#xD;
Best Supportive Care: Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Worsening Covid Symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Anosmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Ageusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The convalescent plasma technology has been replaced by antivirals and monoclonal antibodies. Therefore, the study was not able to accrue successfully and was subsequently terminated.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Joshua Zenreich</name_or_title>
      <organization>Hackensack Meridian Health</organization>
      <phone>551-996-4248</phone>
      <email>Joshua.Zenreich@hmhn.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04456413
org study id: Pro2020-0542
nct id: NCT04456413
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
-  This is a phase II randomized study of convalescent plasma for the treatment of
           non-immune individuals with COVID-19 infection at high risk of complications.

        -  Subjects will be considered as having completed the study after 2 months (+/- 5) days,
           unless consent withdrawal or death occurs first.

        -  Subjects will be randomized to receiving convalescent plasma or best supportive care.

        -  Patients randomized to best supportive care may receive plasma should they require
           hospitalization for progression of COVID-19 disease.

        -  The final analysis will be conducted once the last subject completes the 2-month visit
           or withdraws from the study.
Overall study design

        -  This is a phase II randomized study of convalescent plasma for the treatment of
           non-immune individuals with COVID-19 infection at high risk of complications.

        -  Subjects will be considered as having completed the study after 2 months (+/- 5) days,
           unless consent withdrawal or death occurs first.

        -  Subjects will be randomized to receiving convalescent plasma or best supportive care.

        -  Patients randomized to best supportive care may receive plasma should they require
           hospitalization for progression of COVID-19 disease.

        -  The final analysis will be conducted once the last subject completes the 2-month visit
           or withdraws from the study.

      A total of 306 subjects will be recruited, 153 for each arm. If a patient in the best
      supportive care arm requires hospitalization, the patient will be eligible to receive
      convalescent plasma if requested and/or deemed medically appropriate by the admitting
      physician.

      Overall study duration

        -  The study begins when the first subject (donor or recipient) signs the informed consent.
           The study will end once the last enrolled subject completes the study (likely a
           recipient).

        -  The expected duration of the study is approximately 12 months.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hospitalization Rate
time frame: 10 Days
description: The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.
measure: Time to Symptoms Resolution
time frame: 2 Months
description: The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.
measure: Overall Survival
time frame: 2 Months
description: Overall survival (OS) will be defined as the time in days from study entry to death. Patients who are alive on the date of closing follow-up will be censored on that date.
measure: Rate of Virologic Clearance by Nasopharyngeal Swab at 2 and 4 Weeks
time frame: 2 and 4 Weeks
measure: Rate of Nasopharyngeal Swab Positivity in Donors
time frame: 2 Months
measure: Rate of Donor Titers Level
time frame: 2 Months
measure: Impact of Donor Titers Level on Efficacy
time frame: 2 Months
measure: Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.
time frame: Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months
measure: Plasma Product's Cytokine Level Assessment
time frame: Day 0
description: Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data.
measure: Plasma Product's Mannose-binding Lectin (MBL) Level Assessment
time frame: Day 0
measure: Plasma Product's Procalcitonin (PCT) Level Assessment
time frame: Day 0
measure: Plasma Product's C-reactive Protein (CRP) Level Assessment
time frame: Day 0
measure: Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment
time frame: Day 0
measure: Plasma Product's Annexin V Level Assessment
time frame: Day 0
measure: Plasma Product's Surfactant Protein D (SP-D) Level Assessment
time frame: Day 0
measure: Plasma Product's microRNA Level Assessment
time frame: Day 0
measure: Plasma Product's Immunoglobulin Level Assessment
time frame: Day 0
measure: Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization
time frame: 2 Weeks and 4 Weeks
measure: Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization
time frame: 2 Weeks and 4 Weeks
measure: Rates of Adverse Events Associated With Convalescent Plasma Infusion.
time frame: Day 3 and 7, Weeks 2 and 4
description: Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days).
arm group label: Convalescent Plasma
arm group type: Experimental
description: Fresh or frozen plasma will be infused one time to patients
arm group label: Best Supportive Care
arm group type: Active Comparator
description: Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.
intervention type: Biological
intervention name: Convalescent Plasma
description: Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection
arm group label: Convalescent Plasma
intervention type: Other
intervention name: Best Supportive Care
description: Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.
arm group label: Best Supportive Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michele L Donato, MD
role: Principal Investigator
affiliation: Hackensack Meridian Health
facility: 
country: United States
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PMID: 32192578
citation: Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.
PMID: 7985997
citation: Casadevall A, Scharff MD. Return to the past: the case for antibody-based therapies in infectious diseases. Clin Infect Dis. 1995 Jul;21(1):150-61. doi: 10.1093/clinids/21.1.150.
PMID: 7578724
citation: Casadevall A, Pirofski LA. Antibody-mediated regulation of cellular immunity and the inflammatory response. Trends Immunol. 2003 Sep;24(9):474-8. doi: 10.1016/s1471-4906(03)00228-x. No abstract available.
PMID: 12967670
citation: Casadevall A, Dadachova E, Pirofski LA. Passive antibody therapy for infectious diseases. Nat Rev Microbiol. 2004 Sep;2(9):695-703. doi: 10.1038/nrmicro974.
PMID: 15372080
citation: Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545-1548. doi: 10.1172/JCI138003. No abstract available.
PMID: 32167489
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responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The convalescent plasma technology has been replaced by antivirals and monoclonal antibodies. Therefore, the study was not able to accrue successfully and was subsequently terminated.
point of contact: 