CSSC-004: Convalescent Plasma to Limit SARS-CoV-2 Associated Complications
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 |
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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.
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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
- 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
Inclusion Criteria:
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≥ 18 years of age
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Competent and capable to provide informed consent
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• Positive molecular test for presence of SARS-CoV-2 in fluid collected by saliva for antigen, oropharyngeal or nasopharyngeal swab
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Experiencing any symptoms of COVID-19 including but not limited to fever(T> 100.5º F), cough, or other COVID associated symptoms like anosmia
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≤ 8 days since the first symptoms of COVID-19
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≤ 8 days since first positive SARS-CoV-2 RNA test
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Able and willing to comply with protocol requirements listed in the informed consent
Exclusion Criteria:
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Hospitalized or expected to be hospitalized within 24 hours of enrollment
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Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance
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History of prior reactions to transfusion blood products
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Inability to complete therapy with the study product within 24 hours after enrollment
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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 | |
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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.- IRB00247590
- R01AI152078
- W911QY2090012