CSSC-004: Convalescent Plasma to Limit SARS-CoV-2 Associated Complications

Sponsor
Johns Hopkins University (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04373460
Collaborator
State of Maryland (Other), Bloomberg Foundation (Other), United States Department of Defense (U.S. Fed), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), National Center for Advancing Translational Science (NCATS) (NIH)
1,225
25
2
27.4
49
1.8

Study Details

Study Description

Brief Summary

To assess the efficacy and safety of Human coronavirus immune plasma (HCIP) to reduce the risk of hospitalization or death, the duration of symptoms and duration of nasopharyngeal or oropharyngeal viral shedding.

Condition or Disease Intervention/Treatment Phase
  • Biological: SARS-CoV-2 convalescent plasma
  • Biological: Plasma from a volunteer donor
Phase 2

Detailed Description

The purpose of this randomized, double-blind, controlled, phase 2 trial is to evaluate the efficacy of treatment with HCIP in reducing hospitalization and death prior to hospitalization among outpatient adults who have RNA detection test-confirmed COVID-19 AND have developed any symptoms of COVID-19 including but not limited to fever, cough, or other COVID associated symptoms like anosmia. Ambulatory/outpatient adults subjects 18 years of age or older, regardless of risk factors for severe illness may participate. A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.

Study Design

Study Type:
Interventional
Actual Enrollment :
1225 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Comparison of the Efficacy and Safety of Human Coronavirus Immune Plasma (HCIP) vs. Control (SARS-CoV-2 Non-immune) Plasma Among Outpatients With Symptomatic COVID-19
Actual Study Start Date :
Jun 3, 2020
Actual Primary Completion Date :
Jan 14, 2022
Anticipated Study Completion Date :
Sep 14, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: SARS-CoV-2 convalescent plasma

SARS-CoV-2 convalescent plasma (1 cup; minimum of 175 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 and after July 2021 meets FDA criteria for high titer plasma.

Biological: SARS-CoV-2 convalescent plasma
SARS-CoV-2 convalescent plasma (1 cup; minimum of 175 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 and after July 2021 meets FDA criteria for high titer plasma.
Other Names:
  • Human coronavirus immune plasma (HCIP)
  • Active Comparator: Standard Control plasma

    Plasma collected from a volunteer donor prior to January 1, 2020 will not be tested for SARS-CoV-2 antibodies. Plasma collected after December 31, 2019 will be confirmed as SARS-CoV-2 seronegative.

    Biological: Plasma from a volunteer donor
    Plasma collected from a volunteer donor prior to January 1, 2020 will not be tested for SARS-CoV-2 antibodies. Plasma collected after December 31, 2019 will be confirmed as SARS-CoV-2 seronegative.

    Outcome Measures

    Primary Outcome Measures

    1. Cumulative incidence of hospitalization or death prior to hospitalization [Up to day 28]

      Cumulative incidence measured as the proportion of subjects who were hospitalized or who died prior to hospitalization

    2. Cumulative incidence of treatment-related serious adverse events [Up to day 28]

      Cumulative incidence of treatment-related serious adverse events categorized separately as either severe infusion reactions or Acute Respiratory Distress Syndrome (ARDS) during the study period.

    3. Cumulative incidence of treatment-related grade 3 or higher adverse events [Up to day 90]

      Cumulative incidence measured as the proportion of subjects experiencing a Grade 3 or higher.

    Secondary Outcome Measures

    1. Change in serum SARS-CoV-2 antibody titers [Days 0, 14, 28 and 90]

      Analysis of serum SARS-CoV-2 antibody titers will also primarily be descriptive, comparing the geometric mean titers at day 0, 14, 28 and 90 between the randomized arms and calculating the shift or change in the titer distribution.

    2. Time to SARS-CoV-2 Polymerase Chain Reaction (PCR) negativity [Day 0, 14 and 28]

      Compare the rates and duration of SARS-CoV-2 RNA positivity by Real-Time (RT)-PCR of nasopharyngeal or oropharyngeal fluid between active and control groups at days 0, 14 and 28. PCR results take up to 6 months to process and be available to the study team for data analysis.

    Other Outcome Measures

    1. Change in level of SARS-CoV-2 RNA [Day 0, 14 and 28]

      Compare the levels of SARS-CoV-2 RNA between active and control groups at days 0, 14 and 28. RNA results take up to 6 months to process and be available to the study team for data analysis.

    2. Change in oxygen saturation levels [Day 0 to Day 28 (where available)]

      Comparison of participant self-assessed blood oxygen saturation levels (in percentage oxygen) between treatment arms using pulse oximetry from Day 0 to Day 28.

    3. Rate of participant-reported secondary infection of housemates [Up to day 90]

      Secondary infection will be assessed by measuring the number of individuals that live in the same house as the active arm who became sick by the end of follow-up period.

    4. Time to ICU admission, invasive mechanical ventilation or death in hospital [Up to day 90]

      Disease severity measured by time (in days) to admission to the ICU or , invasive mechanical ventilation or time to death.

    5. Time to resolution of COVID-19 symptoms [Up to day 90]

      Time (in days) to resolution of COVID-19 symptoms will be based on temperature logs and symptom score sheets.

    6. Impact of convalescent plasma on outcome as assessed by change in hospitalization rate [Day 0 to Day 90]

      Assess change in hospitalization rate as measured by number of hospitalizations stratified by age groups <65 and >=65

    7. Impact of donor antibody titers on hospitalization rate of convalescent plasma recipients [Day 0 to Day 90]

      Impact of donor antibody titers (high/low) will be assessed by hospitalization rate as measured by number of hospitalizations.

    8. Impact of donor antibody titers on antibody levels of convalescent plasma recipients [Day 0 to Day 90]

      Impact of donor antibody titers (high/low) will be assessed by antibody levels

    9. Impact of donor antibody titers on viral positivity rates of convalescent plasma recipients [Day 0 to Day 90]

      Impact of donor antibody titers (high/low) will be assessed by viral positivity rates (number of SARS-CoV-2 positive cases per total cases)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • ≥ 18 years of age

    • Competent and capable to provide informed consent

    • • Positive molecular test for presence of SARS-CoV-2 in fluid collected by saliva for antigen, oropharyngeal or nasopharyngeal swab

    • Experiencing any symptoms of COVID-19 including but not limited to fever(T> 100.5º F), cough, or other COVID associated symptoms like anosmia

    • ≤ 8 days since the first symptoms of COVID-19

    • ≤ 8 days since first positive SARS-CoV-2 RNA test

    • Able and willing to comply with protocol requirements listed in the informed consent

    Exclusion Criteria:
    • Hospitalized or expected to be hospitalized within 24 hours of enrollment

    • Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance

    • History of prior reactions to transfusion blood products

    • Inability to complete therapy with the study product within 24 hours after enrollment

    • Receiving any treatment drug for COVID-19 within 14 days prior to screening evaluation (monoclonal antibodies, compassionate use or study trial related). Steroid treatment at any time does not affect study eligibility

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294
    2 Mayo Clinic, Phoenix Phoenix Arizona United States 85054
    3 Center for American Indian Health - Whiteriver Office Whiteriver Arizona United States 85941
    4 University of California, Los Angeles Los Angeles California United States 90095
    5 University of California, Irvine Health Orange California United States 92868
    6 Western Connecticut Health Netowrk, Danbury Hospital Danbury Connecticut United States 06810
    7 Western Connecticut Health Network, Norwalk Hospital Norwalk Connecticut United States 06856
    8 University of Miami Coral Gables Florida United States 33124
    9 University of Miami Clinical Translational Research Site Miami Florida United States 33136
    10 NorthShore University HealthSystem Evanston Illinois United States 60201
    11 Anne Arundel Medical Center Annapolis Maryland United States 21401
    12 The Johns Hopkins University Baltimore Maryland United States 21205
    13 MedStar Washington Hospital Center Hyattsville Maryland United States 20782
    14 University of Massachusetts Worcester Worcester Massachusetts United States 01655
    15 Wayne State University Detroit Michigan United States 48202
    16 University of New Mexico Health Sciences Center Albuquerque New Mexico United States 87131
    17 Center for American Indian Health - Gallup Office Gallup New Mexico United States 87301
    18 Center for American Indian Health - Shiprock Office Shiprock New Mexico United States 87420
    19 Vassar Brothers Medical Center Poughkeepsie New York United States 12601
    20 University of Rochester Rochester New York United States 14642
    21 University of Cincinnati Medical Center Cincinnati Ohio United States 45219
    22 Lifespan/BrownUniversity (Rhode Island Hospital) Providence Rhode Island United States 02903
    23 Baylor College of Medicine Houston Texas United States 77030
    24 University of Texas Health Science Center at Houston Houston Texas United States 77030
    25 The University of Utah Salt Lake City Utah United States 84132

    Sponsors and Collaborators

    • Johns Hopkins University
    • State of Maryland
    • Bloomberg Foundation
    • United States Department of Defense
    • National Institute of Allergy and Infectious Diseases (NIAID)
    • National Center for Advancing Translational Science (NCATS)

    Investigators

    • Principal Investigator: David J Sullivan, MD, The Johns Hopkins University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT04373460
    Other Study ID Numbers:
    • IRB00247590
    • R01AI152078
    • W911QY2090012
    First Posted:
    May 4, 2020
    Last Update Posted:
    Jun 7, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Johns Hopkins University

    Study Results

    No Results Posted as of Jun 7, 2022