Plasma Therapy of COVID-19 in Severely Ill Patients

Study Overview
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Brief Summary
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This randomized blinded multi-center phase 2 trial will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma among adults with severe COVID-19. Adults ≥18 years of age may participate. A total of 219 eligible subjects will be randomized in a 2:1 ratio to receive either high-titer anti-SARS-CoV-2 plasma or non-convalescent fresh frozen plasma (control plasma).

Detailed Description
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There are few effective therapies for coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Exposure to viruses results in an adaptive immune response that commonly include antibodies with neutralization activity. Plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Argentine hemorrhagic fever, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS-CoV). Small clinical trials and observational studies of CP therapy in patients with COVID-19 have suggested a possible clinical benefit.

Official Title
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A Phase 2, Multi-Center, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Human Anti-SARS-CoV-2 Convalescent Plasma in Severely Ill Adults With COVID-19

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: Convalescent Plasma (anti-SARS-CoV-2 plasma)
* Biological: Non-convalescent Plasma (control plasma)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent prior to performing study procedures or have a legally authorized representative available to do so. Age ≥18 years Evidence of SARS-CoV-2 infection by PCR test of naso-/oro-pharyngeal swab or tracheal aspirate sample within 14 days of randomization Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen, non-invasive or invasive mechanical ventilation at screening Evidence of infiltrates on chest radiography Females of childbearing age and males, must be willing to practice an effective contraceptive method or remain abstinent during the study period. Exclusion Criteria: Participation in another clinical trial of anti-viral agent(s) for COVID-19 Receipt of any anti-viral agent(s) with possible activity against SARS-CoV-2 <24 hours prior to study drug administration [1] Mechanically ventilated (including veno-venous (VV)-ECMO) ≥ 5 days Severe multi-organ failure History of prior reactions to transfusion blood products meeting definitive case definition criteria, at least severe severity, and probable or definite imputability per National Healthcare Safety Network (NHSN)/Centers for Disease Control and Prevention (CDC) criteria Known Immunoglobulin A (IgA) deficiency Females who are pregnant Use of remdesivir as treatment for COVID-19 is permitted.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 219 eligible subjects will be randomized in a 2:1 ratio to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or non-convalescent fresh frozen plasma (control plasma).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma (anti-SARS-CoV-2 plasma)<br>Convalescent plasma (1 unit;  200-250 mL) collected from a volunteer who recovered from COVID-19 disease | Biological: Convalescent Plasma (anti-SARS-CoV-2 plasma)<br>* Convalescent Plasma that contains antibody titers against SARS-CoV-2<br>|
| Active Comparator: Non-convalescent Plasma (control plasma)<br>Non-convalescent plasma (1 unit;  200-250 mL) of standard plasma collected prior to December 2019 | Biological: Non-convalescent Plasma (control plasma)<br>* Non-convalescent plasma (does not contain antibody titers against SARS-CoV-2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day 28 severity outcome | Compare the day 28 severity outcome amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups using a 7-point ordinal scale of clinical status. | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of SARS-CoV-2 PCR Positivity | Compare the proportion and duration of SARS-CoV-2 PCR positivity (via RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups at days 0, 7, and 14. | Up to 14 days | 
| Levels of SARS-CoV-2 RNA | Compare levels of SARS-CoV-2 RNA amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups at days 0, 7, and 14. | Up to 14 days | 
| Duration of Need for Supplemental Oxygen | Compare duration of need for supplemental oxygen and/or mechanical ventilation amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. | Up to 28 days | 
| Duration of Hospitalization | Compare duration of hospitalization amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. | Up to 28 days | 
| In-hospital and 28-day mortality | Compare in-hospital and 28-day mortality amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. | Up to 28 days | 
| Time-to-clinical improvement in-hospital | Compare time-to-clinical improvement in-hospital amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups, defined as the time to either an improvement of one point on a 7-point ordinal scale of clinical status or alive discharge from the hospital, whichever comes first. | Up to 28 days | 
| Host genetic differences at day 0 | To assess for host genetic differences at Day 0 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. | Day 0 | 
| Host transcriptomic differences at days 0,7,14 | To assess for host transcriptomic differences at Day 0,7,14 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. | Up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, COVID, Coronavirus, Convalescent plasma