<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/NCT04411602</url>
  </required_header>
  <id_info>
    <org_study_id>1589349</org_study_id>
    <nct_id>NCT04411602</nct_id>
  </id_info>
  <brief_title>Intermediate IND Severe Illness COVID-19 CP</brief_title>
  <official_title>Intermediate IND Severe Illness COVID-19 CP</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ascension South East Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ascension South East Michigan</source>
  <oversight_info>
    <has_dmc>No</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>
      Beyond supportive care, there are currently no proven therapeutic options for pneumonia due&#xD;
      to coronavirus disease (COVID-19), the infection caused by Severe Acute Respiratory Syndrome&#xD;
      Coronavirus 2 (SARS-CoV-2). Human convalescent plasma is an option for treatment of COVID-19&#xD;
      and will be available when sufficient numbers of people have recovered. Such persons should&#xD;
      have high titer neutralizing immunoglobulin-containing plasma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will receive open-label screened plasma from COVID-19+ clinically resolved&#xD;
      individuals (≥14 days post-resolution). Dosing of single or double plasma units (weight based&#xD;
      &lt; and &gt; 90Kg) will be administered on days 0, 2, 4, 6, and 8 (based on plasma availability),&#xD;
      or until futility (if either occurs before day 8) is determined by the ICU. Doses can be&#xD;
      omitted at the discretion of the treating clinician (e.g., TRALI events are 100%&#xD;
      donor-dependent and do not prohibit future transfusions).&#xD;
&#xD;
      The study drug is the investigational product, anti-SARS-CoV-2 convalescent plasma obtained&#xD;
      from the American Red Cross or local plasma supply (medicDal center or city/region-wide&#xD;
      shared blood bank) from patients identified as having recovered from COVID-19. Donors and&#xD;
      samples will be screened for infections transmitted via transfusion (e.g. HIV, HBV, HCV, WNV,&#xD;
      HTLV-I/II, T.cruzi, ZIKV) both through the use of the uniform donor questionnaire and FDA&#xD;
      mandated blood donor screening tests. Plasma will be collected using apheresis technology or&#xD;
      whole blood collection in accordance with standard FDA and blood bank protocols.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No participants due to waning pandemic.&#xD;
  </why_stopped>
  <start_date type="Actual">April 7, 2020</start_date>
  <completion_date type="Actual">April 7, 2021</completion_date>
  <primary_completion_date type="Actual">April 7, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Severely ill patients with COVID-19 severe respiratory distress</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Transfusion of patients in the ICU with convalescent plasma for COVID-19-induced respiratory failure.</measure>
    <time_frame>Track patient progress for 28 days post initial convalescent dose.</time_frame>
    <description>Identification of patient population in ICU that are in acute respiratory failure due to COVID-19 and transfuse with convalescent plasma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilatory free days</measure>
    <time_frame>Track patient progress for 28 days post initial convalescent dose.</time_frame>
    <description>Measure reduction in ventilator use and/or changes in mechanical ventilator parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient mortality (including death from any cause)</measure>
    <time_frame>Track patient progress for 28 days post initial convalescent dose.</time_frame>
    <description>Measure length of stay from the time of admission to the hospital and subsequent admission to the ICU. Document resolution of COVID-19 infection or alternatively patient death.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Severe Acute Respiratory Syndrome</condition>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Treatment with Convalescent Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SARS-CoV-2 convalescent plasma from approved donors will be transfused into severely ill patients with confirmed COVID-19 severe respiratory distress. Plasma will be administered on days 0, 2,4, 6 and 8.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SARS-CoV-2 plasma</intervention_name>
    <description>To determine feasibility of convalescent plasma for treating patients in the ICU with COVID-19.</description>
    <arm_group_label>Treatment with Convalescent Plasma</arm_group_label>
    <other_name>Convalescent plasma</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Laboratory confirmed COVID-19&#xD;
&#xD;
          -  Severe or Immediately life threatening COVID-19&#xD;
&#xD;
          -  Dyspnea&#xD;
&#xD;
          -  Respiratory frequency &gt; 30/minute&#xD;
&#xD;
          -  Blood oxygen saturation &lt;93%&#xD;
&#xD;
          -  Life-threatening disease is defined as the following&#xD;
&#xD;
          -  Respiratory Failure.&#xD;
&#xD;
          -  Septic shock, and/or,&#xD;
&#xD;
          -  Multiple organ dysfunction or failure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to transfusion (severe volume overload, history of anaphylaxis to&#xD;
             blood products).&#xD;
&#xD;
          -  Other documented uncontrolled infection.&#xD;
&#xD;
          -  Severe DIC needing factor replacement, FFP, cryoprecipitate.&#xD;
&#xD;
          -  On dialysis.&#xD;
&#xD;
          -  Active intracranial bleeding.&#xD;
&#xD;
          -  Clinically significant myocardial ischemia.&#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>Shukri David, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ascension Providence Hospital, Southfield Campus</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Debra J Levan, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ascension Macomb-Oakland Hospital, Warren Campus</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ascension Providence Hospital, Novi Campus</name>
      <address>
        <city>Novi</city>
        <state>Michigan</state>
        <zip>48374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Providence Hospital, Southfield Campus</name>
      <address>
        <city>Southfield</city>
        <state>Michigan</state>
        <zip>48075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Macomb-Oakland Hospital, Warren Campus</name>
      <address>
        <city>Warren</city>
        <state>Michigan</state>
        <zip>48093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>7578724</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>15372080</PMID>
  </reference>
  <reference>
    <citation>Zhang JS, Chen JT, Liu YX, Zhang ZS, Gao H, Liu Y, Wang X, Ning Y, Liu YF, Gao Q, Xu JG, Qin C, Dong XP, Yin WD. A serological survey on neutralizing antibody titer of SARS convalescent sera. J Med Virol. 2005 Oct;77(2):147-50. doi: 10.1002/jmv.20431.</citation>
    <PMID>16121363</PMID>
  </reference>
  <reference>
    <citation>Sahr F, Ansumana R, Massaquoi TA, Idriss BR, Sesay FR, Lamin JM, Baker S, Nicol S, Conton B, Johnson W, Abiri OT, Kargbo O, Kamara P, Goba A, Russell JB, Gevao SM. Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone. J Infect. 2017 Mar;74(3):302-309. doi: 10.1016/j.jinf.2016.11.009. Epub 2016 Nov 17.</citation>
    <PMID>27867062</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>12967670</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>7985997</PMID>
  </reference>
  <reference>
    <citation>Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.</citation>
    <PMID>15616839</PMID>
  </reference>
  <reference>
    <citation>Yeh KM, Chiueh TS, Siu LK, Lin JC, Chan PK, Peng MY, Wan HL, Chen JH, Hu BS, Perng CL, Lu JJ, Chang FY. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. doi: 10.1093/jac/dki346. Epub 2005 Sep 23.</citation>
    <PMID>16183666</PMID>
  </reference>
  <reference>
    <citation>Ko JH, Seok H, Cho SY, Ha YE, Baek JY, Kim SH, Kim YJ, Park JK, Chung CR, Kang ES, Cho D, Muller MA, Drosten C, Kang CI, Chung DR, Song JH, Peck KR. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617-622. doi: 10.3851/IMP3243. Epub 2018 Jun 20.</citation>
    <PMID>29923831</PMID>
  </reference>
  <reference>
    <citation>Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis. 2016 Sep;22(9):1554-61. doi: 10.3201/eid2209.151164.</citation>
    <PMID>27532807</PMID>
  </reference>
  <reference>
    <citation>van Erp EA, Luytjes W, Ferwerda G, van Kasteren PB. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front Immunol. 2019 Mar 22;10:548. doi: 10.3389/fimmu.2019.00548. eCollection 2019.</citation>
    <PMID>30967872</PMID>
  </reference>
  <reference>
    <citation>Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J, Shi Z, Zhou Y, Du L, Li F. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol. 2020 Feb 14;94(5):e02015-19. doi: 10.1128/JVI.02015-19. Print 2020 Feb 14.</citation>
    <PMID>31826992</PMID>
  </reference>
  <reference>
    <citation>Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.</citation>
    <PMID>25030060</PMID>
  </reference>
  <reference>
    <citation>Crowe JE Jr, Firestone CY, Murphy BR. Passively acquired antibodies suppress humoral but not cell-mediated immunity in mice immunized with live attenuated respiratory syncytial virus vaccines. J Immunol. 2001 Oct 1;167(7):3910-8. doi: 10.4049/jimmunol.167.7.3910.</citation>
    <PMID>11564809</PMID>
  </reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>July 6, 2021</last_update_submitted>
  <last_update_submitted_qc>July 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Corona Virus</keyword>
  <keyword>Convalescent plasma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Severe Acute Respiratory Syndrome</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/NCT04411602
org study id: 1589349
nct id: NCT04411602
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Beyond supportive care, there are currently no proven therapeutic options for pneumonia due
      to coronavirus disease (COVID-19), the infection caused by Severe Acute Respiratory Syndrome
      Coronavirus 2 (SARS-CoV-2). Human convalescent plasma is an option for treatment of COVID-19
      and will be available when sufficient numbers of people have recovered. Such persons should
      have high titer neutralizing immunoglobulin-containing plasma.
Subjects will receive open-label screened plasma from COVID-19+ clinically resolved
      individuals (≥14 days post-resolution). Dosing of single or double plasma units (weight based
      < and > 90Kg) will be administered on days 0, 2, 4, 6, and 8 (based on plasma availability),
      or until futility (if either occurs before day 8) is determined by the ICU. Doses can be
      omitted at the discretion of the treating clinician (e.g., TRALI events are 100%
      donor-dependent and do not prohibit future transfusions).

      The study drug is the investigational product, anti-SARS-CoV-2 convalescent plasma obtained
      from the American Red Cross or local plasma supply (medicDal center or city/region-wide
      shared blood bank) from patients identified as having recovered from COVID-19. Donors and
      samples will be screened for infections transmitted via transfusion (e.g. HIV, HBV, HCV, WNV,
      HTLV-I/II, T.cruzi, ZIKV) both through the use of the uniform donor questionnaire and FDA
      mandated blood donor screening tests. Plasma will be collected using apheresis technology or
      whole blood collection in accordance with standard FDA and blood bank protocols.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Severely ill patients with COVID-19 severe respiratory distress
primary purpose: Treatment
masking: None (Open Label)
measure: Transfusion of patients in the ICU with convalescent plasma for COVID-19-induced respiratory failure.
time frame: Track patient progress for 28 days post initial convalescent dose.
description: Identification of patient population in ICU that are in acute respiratory failure due to COVID-19 and transfuse with convalescent plasma
measure: Ventilatory free days
time frame: Track patient progress for 28 days post initial convalescent dose.
description: Measure reduction in ventilator use and/or changes in mechanical ventilator parameters
measure: Patient mortality (including death from any cause)
time frame: Track patient progress for 28 days post initial convalescent dose.
description: Measure length of stay from the time of admission to the hospital and subsequent admission to the ICU. Document resolution of COVID-19 infection or alternatively patient death.
arm group label: Treatment with Convalescent Plasma
arm group type: Experimental
description: SARS-CoV-2 convalescent plasma from approved donors will be transfused into severely ill patients with confirmed COVID-19 severe respiratory distress. Plasma will be administered on days 0, 2,4, 6 and 8.
intervention type: Drug
intervention name: SARS-CoV-2 plasma
description: To determine feasibility of convalescent plasma for treating patients in the ICU with COVID-19.
arm group label: Treatment with Convalescent Plasma
other name: Convalescent plasma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shukri David, MD
role: Principal Investigator
affiliation: Ascension Providence Hospital, Southfield Campus
last name: Debra J Levan, DO
role: Principal Investigator
affiliation: Ascension Macomb-Oakland Hospital, Warren Campus
facility: 
facility: 
facility: 
country: United States
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, 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: Zhang JS, Chen JT, Liu YX, Zhang ZS, Gao H, Liu Y, Wang X, Ning Y, Liu YF, Gao Q, Xu JG, Qin C, Dong XP, Yin WD. A serological survey on neutralizing antibody titer of SARS convalescent sera. J Med Virol. 2005 Oct;77(2):147-50. doi: 10.1002/jmv.20431.
PMID: 16121363
citation: Sahr F, Ansumana R, Massaquoi TA, Idriss BR, Sesay FR, Lamin JM, Baker S, Nicol S, Conton B, Johnson W, Abiri OT, Kargbo O, Kamara P, Goba A, Russell JB, Gevao SM. Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone. J Infect. 2017 Mar;74(3):302-309. doi: 10.1016/j.jinf.2016.11.009. Epub 2016 Nov 17.
PMID: 27867062
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, 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: Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.
PMID: 15616839
citation: Yeh KM, Chiueh TS, Siu LK, Lin JC, Chan PK, Peng MY, Wan HL, Chen JH, Hu BS, Perng CL, Lu JJ, Chang FY. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. doi: 10.1093/jac/dki346. Epub 2005 Sep 23.
PMID: 16183666
citation: Ko JH, Seok H, Cho SY, Ha YE, Baek JY, Kim SH, Kim YJ, Park JK, Chung CR, Kang ES, Cho D, Muller MA, Drosten C, Kang CI, Chung DR, Song JH, Peck KR. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617-622. doi: 10.3851/IMP3243. Epub 2018 Jun 20.
PMID: 29923831
citation: Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis. 2016 Sep;22(9):1554-61. doi: 10.3201/eid2209.151164.
PMID: 27532807
citation: van Erp EA, Luytjes W, Ferwerda G, van Kasteren PB. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front Immunol. 2019 Mar 22;10:548. doi: 10.3389/fimmu.2019.00548. eCollection 2019.
PMID: 30967872
citation: Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J, Shi Z, Zhou Y, Du L, Li F. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol. 2020 Feb 14;94(5):e02015-19. doi: 10.1128/JVI.02015-19. Print 2020 Feb 14.
PMID: 31826992
citation: Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.
PMID: 25030060
citation: Crowe JE Jr, Firestone CY, Murphy BR. Passively acquired antibodies suppress humoral but not cell-mediated immunity in mice immunized with live attenuated respiratory syncytial virus vaccines. J Immunol. 2001 Oct 1;167(7):3910-8. doi: 10.4049/jimmunol.167.7.3910.
PMID: 11564809
responsible party type: Sponsor
mesh term: Severe Acute Respiratory Syndrome