SARS-CoV-2 Infection
Conditions
Keywords
COVID-19, COVID, Coronavirus, Convalescent plasma
Brief summary
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
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.
Interventions
Convalescent Plasma that contains antibody titers against SARS-CoV-2
BIOLOGICALNon-convalescent Plasma (control plasma)
Non-convalescent plasma (does not contain antibody titers against SARS-CoV-2)
Sponsors
New York Blood Center
Amazon, Inc.
Max O'Donnell
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 1. Use of remdesivir as treatment for COVID-19 is permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Up to 28 days | 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. Seven-point ordinal scale for clinical assessment ranges from 1 and 2: Not hospitalized 3: Hospitalized, not requiring supplemental oxygen 4: Hospitalized, requiring supplemental oxygen 5: Hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation 6: Hospitalized, requiring IMV, ECMO, or both 7: Dead Higher number means worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of SARS-CoV-2 RNA | Up to 14 days | 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. |
| Duration of Need for Supplemental Oxygen | Up to 28 days | Compare duration of need for supplemental oxygen and/or mechanical ventilation amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. |
| Duration of Hospitalization | Up to 28 days | Compare duration of hospitalization amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. |
| Proportion of SARS-CoV-2 PCR Positivity | Up to 14 days | 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. |
| Time-to-clinical Improvement In-hospital | Up to 28 days | 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 clinical status or alive discharge from the hospital, whichever comes first. |
| Host Genetic Differences at Day 0 | Day 0 | To assess for host genetic differences at Day 0 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. |
| Host Transcriptomic Differences at Days 0,7,14 | Up to 14 days | To assess for host transcriptomic differences at Day 0,7,14 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. |
| 28-day Mortality | Up to 28 days | Compare up to 28-day mortality amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups. |
Countries
Brazil, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) Convalescent plasma (1 unit; \
200-250 mL) collected from a volunteer who recovered from COVID-19 disease
Convalescent Plasma (anti-SARS-CoV-2 plasma): Convalescent Plasma that contains antibody titers against SARS-CoV-2 | 150 |
| Non-convalescent Plasma (Control Plasma) Non-convalescent plasma (1 unit; \
200-250 mL) of standard plasma collected prior to December 2019
Non-convalescent Plasma (control plasma): Non-convalescent plasma (does not contain antibody titers against SARS-CoV-2) | 73 |
| Total | 223 |
Baseline characteristics
| Characteristic | Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Non-convalescent Plasma (Control Plasma) | Total |
|---|---|---|---|
| Age, Customized 60 - 69 years old | 35 Participants | 24 Participants | 59 Participants |
| Age, Customized < 60 years old | 74 Participants | 28 Participants | 102 Participants |
| Age, Customized 70 - 79 years old | 28 Participants | 16 Participants | 44 Participants |
| Age, Customized >= 80 years old | 13 Participants | 5 Participants | 18 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Brazil | 101 participants | 49 participants | 150 participants |
| Region of Enrollment United States | 49 participants | 24 participants | 73 participants |
| Sex: Female, Male Female | 96 Participants | 51 Participants | 147 Participants |
| Sex: Female, Male Male | 54 Participants | 22 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 150 | 18 / 73 |
| other Total, other adverse events | 4 / 147 | 3 / 72 |
| serious Total, serious adverse events | 39 / 147 | 26 / 72 |
Outcome results
Primary
Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status
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. Seven-point ordinal scale for clinical assessment ranges from 1 and 2: Not hospitalized 3: Hospitalized, not requiring supplemental oxygen 4: Hospitalized, requiring supplemental oxygen 5: Hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation 6: Hospitalized, requiring IMV, ECMO, or both 7: Dead Higher number means worse outcome
Time frame: Up to 28 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, requiring supplemental oxygen | 7 Participants |
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, requiring IMV, ECMO, or both | 12 Participants |
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, not requiring supplemental oxygen | 3 Participants |
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Dead | 19 Participants |
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation | 1 Participants |
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Not hospitalized | 108 Participants |
| Non-convalescent Plasma (Control Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Not hospitalized | 48 Participants |
| Non-convalescent Plasma (Control Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, not requiring supplemental oxygen | 2 Participants |
| Non-convalescent Plasma (Control Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, requiring supplemental oxygen | 1 Participants |
| Non-convalescent Plasma (Control Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation | 0 Participants |
| Non-convalescent Plasma (Control Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Hospitalized, requiring IMV, ECMO, or both | 4 Participants |
| Non-convalescent Plasma (Control Plasma) | Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status | Dead | 18 Participants |
Secondary
28-day Mortality
Compare up to 28-day mortality amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Time frame: Up to 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | 28-day Mortality | 19 Participants |
| Non-convalescent Plasma (Control Plasma) | 28-day Mortality | 18 Participants |
Secondary
Duration of Hospitalization
Compare duration of hospitalization amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Duration of Hospitalization | 9 days |
| Non-convalescent Plasma (Control Plasma) | Duration of Hospitalization | 8 days |
Secondary
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.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Duration of Need for Supplemental Oxygen | 6 days |
| Non-convalescent Plasma (Control Plasma) | Duration of Need for Supplemental Oxygen | 7 days |
Secondary
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.
Time frame: Day 0
Population: Data was not collected or analyzed.
Secondary
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.
Time frame: Up to 14 days
Population: Data was not collected or analyzed.
Secondary
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.
Time frame: Up to 14 days
Population: Data was not collected or analyzed.
Secondary
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.
Time frame: Up to 14 days
Population: Data was not collected or analyzed.
Secondary
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 clinical status or alive discharge from the hospital, whichever comes first.
Time frame: Up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Convalescent Plasma (Anti-SARS-CoV-2 Plasma) | Time-to-clinical Improvement In-hospital | 5 days |
| Non-convalescent Plasma (Control Plasma) | Time-to-clinical Improvement In-hospital | 7 days |