<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/NCT04457726</url>
  </required_header>
  <id_info>
    <org_study_id>COVID-T 2.0</org_study_id>
    <nct_id>NCT04457726</nct_id>
  </id_info>
  <brief_title>Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19</brief_title>
  <official_title>Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>KK Women's and Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Duke-NUS Graduate Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Singapore General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sengkang General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Changi General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>KK Women's and Children's Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective of this project is to develop an emergent treatment protocol using&#xD;
      adoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis is that&#xD;
      SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be&#xD;
      manufactured expeditiously and these cells are safe and effective for the treatment of severe&#xD;
      SARS-CoV-2 infections.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of&#xD;
      Coronavirus Disease 2019 (COVID-19). Currently, no vaccine has been proven to be effective.&#xD;
      While waiting for vaccine to be developed, passive immunity can be acquired immediately by&#xD;
      adoptive transfer of SARS-CoV-2 specific T cells from convalescent donors into newly infected&#xD;
      patients.&#xD;
&#xD;
      The overall objective of this project is to develop an emergent treatment protocol using&#xD;
      adoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis is that&#xD;
      SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be&#xD;
      manufactured expeditiously and these cells are safe and effective for the treatment of severe&#xD;
      SARS-CoV-2 infections. Part Two of this project is to assess the safety and efficacy of these&#xD;
      T cells in patients with COVID-19.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">March 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-Limiting Toxicities</measure>
    <time_frame>till Day 28 after infusion of SARS-CoV-2 specific T cells</time_frame>
    <description>Dose-limiting toxicities are defined as &gt;Grade 3 Common Toxicity Criteria associated with the therapeutic cells. Toxicity rate will be summarized descriptively.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>National Early Warning Score (NEWS)</measure>
    <time_frame>one month</time_frame>
    <description>Measured by change in daily NEWS score after infusion of SARS-CoV-2 specific T cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to improvement by one category on a WHO ordinal scale</measure>
    <time_frame>one month</time_frame>
    <description>Measured by time-to-improvement by one category on a WHO ordinal scale after infusion of SARS-CoV-2 specific T cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells</measure>
    <time_frame>two months</time_frame>
    <description>Measured by time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood circulation</measure>
    <time_frame>two months</time_frame>
    <description>Measured by the duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion</measure>
    <time_frame>two months</time_frame>
    <description>Measured by the time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) at 3 months after infusion of SARS-CoV-2 specific T cells</measure>
    <time_frame>three months</time_frame>
    <description>Measured by the proportion of recipients surviving at 3 months after infusion of SARS-CoV-2 specific T cells</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Recipients with severe COVID-19</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recipients who are confirmed positive by SARS-CoV-2 testing and have severe COVID-19.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Recipients with mild to moderate COVID-19</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recipients who are confirmed positive by SARS-CoV-2 testing and have mild to moderate COVID-19.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SARS-CoV-2 Specific T Cells</intervention_name>
    <description>Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.</description>
    <arm_group_label>Recipients with mild to moderate COVID-19</arm_group_label>
    <arm_group_label>Recipients with severe COVID-19</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 1 to 90 years&#xD;
&#xD;
          -  Tested positive for SARS-CoV-2 &lt;72 hours prior to enrolment&#xD;
&#xD;
          -  Predicted to have high chance of mortality:&#xD;
&#xD;
        Group 1: Severe disease, defined by one or more of the following:&#xD;
&#xD;
          -  Dyspnea&#xD;
&#xD;
          -  Respiratory frequency ≥ 30/min&#xD;
&#xD;
          -  Blood oxygen saturation ≤ 93%&#xD;
&#xD;
          -  Partial pressure of arterial oxygen to fraction of inspired oxygen ratio &lt; 300&#xD;
&#xD;
          -  Lung infiltrates &gt; 50% within 24 to 48 hours&#xD;
&#xD;
          -  Respiratory failure&#xD;
&#xD;
          -  Septic shock&#xD;
&#xD;
          -  Multiple organ dysfunction or failure&#xD;
&#xD;
        Group 2: Mild to moderate disease, at high risk of progression to severe disease. For&#xD;
        example,&#xD;
&#xD;
          -  Age &gt; 65 years&#xD;
&#xD;
          -  Chronic health conditions such as chronic lung disease, cardiovascular disease,&#xD;
             diabetes mellitus, obesity, end-stage renal disease or liver disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Rapidly progressive disease with anticipated life-expectancy &lt;72 hours&#xD;
&#xD;
          -  Receiving steroid (&gt;0.5mg/kg methylprednisolone equivalent)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wing Hang Leung</last_name>
    <role>Principal Investigator</role>
    <affiliation>KK Hospital, SingHealth Duke NUS</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Michaela Seng</last_name>
    <phone>82487085</phone>
    <email>bmtct@kkh.com.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>Changi General Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roshni Sadashiv Gokhale</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>KK Women's and Children's Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michaela Seng</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lip Kun Tan</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sengkang General Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiashen Loh</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yeh Ching Linn</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <!-- 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/NCT04457726
org study id: COVID-T 2.0
nct id: NCT04457726
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The overall objective of this project is to develop an emergent treatment protocol using
      adoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis is that
      SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be
      manufactured expeditiously and these cells are safe and effective for the treatment of severe
      SARS-CoV-2 infections.
A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of
      Coronavirus Disease 2019 (COVID-19). Currently, no vaccine has been proven to be effective.
      While waiting for vaccine to be developed, passive immunity can be acquired immediately by
      adoptive transfer of SARS-CoV-2 specific T cells from convalescent donors into newly infected
      patients.

      The overall objective of this project is to develop an emergent treatment protocol using
      adoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis is that
      SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be
      manufactured expeditiously and these cells are safe and effective for the treatment of severe
      SARS-CoV-2 infections. Part Two of this project is to assess the safety and efficacy of these
      T cells in patients with COVID-19.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-Limiting Toxicities
time frame: till Day 28 after infusion of SARS-CoV-2 specific T cells
description: Dose-limiting toxicities are defined as >Grade 3 Common Toxicity Criteria associated with the therapeutic cells. Toxicity rate will be summarized descriptively.
measure: National Early Warning Score (NEWS)
time frame: one month
description: Measured by change in daily NEWS score after infusion of SARS-CoV-2 specific T cells
measure: Time to improvement by one category on a WHO ordinal scale
time frame: one month
description: Measured by time-to-improvement by one category on a WHO ordinal scale after infusion of SARS-CoV-2 specific T cells
measure: Time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells
time frame: two months
description: Measured by time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells
measure: Duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood circulation
time frame: two months
description: Measured by the duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood
measure: Time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion
time frame: two months
description: Measured by the time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion
measure: Overall survival (OS) at 3 months after infusion of SARS-CoV-2 specific T cells
time frame: three months
description: Measured by the proportion of recipients surviving at 3 months after infusion of SARS-CoV-2 specific T cells
arm group label: Recipients with severe COVID-19
arm group type: Experimental
description: Recipients who are confirmed positive by SARS-CoV-2 testing and have severe COVID-19.
arm group label: Recipients with mild to moderate COVID-19
arm group type: Experimental
description: Recipients who are confirmed positive by SARS-CoV-2 testing and have mild to moderate COVID-19.
intervention type: Biological
intervention name: SARS-CoV-2 Specific T Cells
description: Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.
arm group label: Recipients with mild to moderate COVID-19
arm group label: Recipients with severe COVID-19
criteria: 
gender: All
minimum age: 1 Year
maximum age: 90 Years
healthy volunteers: No
last name: Wing Hang Leung
role: Principal Investigator
affiliation: KK Hospital, SingHealth Duke NUS
last name: Michaela Seng
phone: 82487085
email: bmtct@kkh.com.sg
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Singapore
responsible party type: Sponsor
mesh term: COVID-19