Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04373460
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : April 8, 2021
Sponsor:
Collaborators:
State of Maryland
Bloomberg Foundation
United States Department of Defense
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE April 30, 2020
First Posted Date  ICMJE May 4, 2020
Last Update Posted Date April 8, 2021
Actual Study Start Date  ICMJE June 3, 2020
Estimated Primary Completion Date December 21, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2020)
  • Cumulative incidence of hospitalization or death prior to hospitalization [ Time Frame: Up to day 28 ]
    Cumulative incidence measured as the proportion of subjects who were hospitalized or who died prior to hospitalization
  • Cumulative incidence of treatment-related serious adverse events [ Time Frame: 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.
  • Cumulative incidence of treatment-related grade 3 or higher adverse events [ Time Frame: Up to day 90 ]
    Cumulative incidence measured as the proportion of subjects experiencing a Grade 3 or higher.
Original Primary Outcome Measures  ICMJE
 (submitted: April 30, 2020)
  • Cumulative incidence of hospitalization or death prior to hospitalization [ Time Frame: Up to day 28 ]
    Cumulative incidence measured as the proportion of subjects who were hospitalized or who died prior to hospitalization
  • Cumulative incidence of treatment-related serious adverse events [ Time Frame: Up to day 28 ]
    Cumulative incidence measured as the proportion of subjects experiencing an Serious Adverse Event (SAE).
  • Cumulative incidence of treatment-related grade 3 or higher adverse events [ Time Frame: Up to day 90 ]
    Cumulative incidence measured as the proportion of subjects experiencing a Grade 3 or higher.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2020)
  • Change in serum SARS-CoV-2 antibody titers [ Time Frame: 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.
  • Time to SARS-CoV-2 Polymerase Chain Reaction (PCR) negativity [ Time Frame: Day 0, 14 and 28 ]
    Compare the rates and duration of SARS-CoV-2 RNA positivity (by RT-PCR) of nasopharyngeal or oropharyngeal fluid between active and control groups at days 0, 14 and 28
Original Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2020)
  • Change in serum SARS-CoV-2 antibody titers [ Time Frame: 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.
  • Time to SARS-CoV-2 Polymerase Chain Reaction (PCR) negativity [ Time Frame: Up to day 28 ]
    Duration in days of SARS-CoV-2 PCR time to negativity will be analyzed by calculating the number of days taken for a positive participant to lose positivity from day 0 to day 28.
Current Other Pre-specified Outcome Measures
 (submitted: July 15, 2020)
  • Change in level of SARS-CoV-2 RNA [ Time Frame: Day 0, 14 and 28 ]
    Compare the levels of SARS-CoV-2 RNA between active and control groups at days 0, 14 and 28
  • Change in oxygen saturation levels [ Time Frame: 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.
  • Rate of participant-reported secondary infection of housemates [ Time Frame: 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.
  • Time to ICU admission, invasive mechanical ventilation or death in hospital [ Time Frame: Up to day 90 ]
    Disease severity measured by time (in days) to admission to the ICU or , invasive mechanical ventilation or time to death.
  • Time to resolution of COVID-19 symptoms [ Time Frame: Up to day 90 ]
    Time (in days) to resolution of COVID-19 symptoms will be based on temperature logs and symptom score sheets.
  • Impact of convalescent plasma on outcome as assessed by change in hospitalization rate [ Time Frame: Day 0 to Day 90 ]
    Assess change in hospitalization rate as measured by number of hospitalizations stratified by age groups <65 and >=65
  • Impact of donor antibody titers on hospitalizaton rate of convalescent plasma recipients [ Time Frame: Day 0 to Day 90 ]
    Impact of donor antibody titers (high/low) will be assessed by hospitalization rate as measured by number of hospitalizations.
  • Impact of donor antibody titers on antibody levels of convalescent plasma recipients [ Time Frame: Day 0 to Day 90 ]
    Impact of donor antibody titers (high/low) will be assessed by antibody levels
  • Impact of donor antibody titers on viral positivity rates of convalescent plasma recipients [ Time Frame: 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)
Original Other Pre-specified Outcome Measures
 (submitted: April 30, 2020)
  • Change in level of SARS-CoV-2 RNA [ Time Frame: Day 0 to Day 28 ]
    Change in levels of SARS-CoV-2 RNA between randomized arms from Day 0 to Day 28.
  • Change in oxygen saturation levels [ Time Frame: Day 0 to Day 28 ]
    Comparison of participant self-assessed blood oxygen saturation levels (in percentage oxygen) between treatment arms using pulse oximetry from Day 0 to Day 28.
  • Rate of participant-reported secondary infection of housemates [ Time Frame: 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.
  • Time to ICU admission, invasive mechanical ventilation or death in hospital [ Time Frame: Up to day 90 ]
    Disease severity measured by time (in days) to admission to the ICU or , invasive mechanical ventilation or time to death.
  • Time to resolution of COVID-19 symptoms [ Time Frame: Up to day 90 ]
    Time (in days) to resolution of COVID-19 symptoms will be based on temperature logs and symptom score sheets.
  • Impact of convalescent plasma on outcome as assessed by change in hospitalization rate [ Time Frame: Day 0 to Day 90 ]
    Assess change in hospitalization rate as measured by number of hospitalizations stratified by age groups <65 and >=65
  • Impact of donor antibody titers on hospitalizaton rate of convalescent plasma recipients [ Time Frame: Day 0 to Day 90 ]
    Impact of donor antibody titers (high/low) will be assessed by hospitalization rate as measured by number of hospitalizations.
  • Impact of donor antibody titers on antibody levels of convalescent plasma recipients [ Time Frame: Day 0 to Day 90 ]
    Impact of donor antibody titers (high/low) will be assessed by antibody levels
  • Impact of donor antibody titers on viral positivity rates of convalescent plasma recipients [ Time Frame: 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)
 
Descriptive Information
Brief Title  ICMJE Convalescent Plasma to Limit SARS-CoV-2 Associated Complications
Official Title  ICMJE 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
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.
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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
A total of approximately 1344 eligible subjects stratified 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
Condition  ICMJE SARS-CoV 2
Intervention  ICMJE
  • Biological: SARS-CoV-2 convalescent plasma
    Plasma collected by apheresis from a volunteer donor who has recovered from COVID-19 and who has SARS-CoV-2 antibody (titer ≥ 1:320 or current FDA standard titer)
    Other Name: Human coronavirus immune plasma (HCIP)
  • Biological: Plasma from a volunteer donor
    Plasma collected from a volunteer donor prior to December 31, 2019
Study Arms  ICMJE
  • Experimental: SARS-CoV-2 convalescent plasma
    SARS-CoV-2 convalescent plasma (1 cup; ~200-250 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320
    Intervention: Biological: SARS-CoV-2 convalescent plasma
  • 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.
    Intervention: Biological: Plasma from a volunteer donor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 30, 2020)
1344
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2023
Estimated Primary Completion Date December 21, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ≥ 18 years of age
  • Competent and capable to provide informed consent
  • Positive RNA test for presence of SARS-CoV-2 in fluid collected by 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 (off label like hydroxychloroquine, compassionate use or study trial related)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David J Sullivan, MD 410-502-2522 dsulliv7@jhmi.edu
Contact: David Sullivan, MD 410-502-2522 dsulliv7@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04373460
Other Study ID Numbers  ICMJE IRB00247590
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual participant data (IPD) collected in this study, including data dictionaries, will be made available to other researchers after the end of the study.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: After publication of initial study manuscript
Access Criteria: Public
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE
  • State of Maryland
  • Bloomberg Foundation
  • United States Department of Defense
  • National Institute of Allergy and Infectious Diseases (NIAID)
Investigators  ICMJE
Principal Investigator: David J Sullivan, MD The Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP