SARS-CoV 2
Conditions
Keywords
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 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.
Interventions
BIOLOGICALSARS-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.
BIOLOGICALPlasma 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.
Sponsors
State of Maryland
Bloomberg Philanthropies
United States Department of Defense
National Institute of Allergy and Infectious Diseases (NIAID)
National Center for Advancing Translational Sciences (NCATS)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization | Up to day 28 | Cumulative Number measured as the proportion of subjects who were hospitalized or who died prior to hospitalization |
| Cumulative Incidence of Severe Infusion Reactions | Up to day 28 | Cumulative incidence measured as rate per person-years experiencing treatment-related severe infusion reactions during the study period. |
| Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events | Up to day 90 | Cumulative incidence measured as rate per person-years experiencing a Grade 3 or higher. |
| Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS) | Up to day 28 | Cumulative incidence measured as rate per person-years of treatment-related severe Acute Respiratory Distress Syndrome (ARDS) during the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum SARS-CoV-2 Antibody Titers by Visit | Days 0, 14, 28 and 90 | Geometric mean Spike Receptor Binding Domain (RBD) titers at day 0, 14, 28 and 90 between the randomized arms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Resolved COVID-19 Symptoms at Day 90 | Day 90 | Number of participants with resolved COVID-19 symptoms at day 90 |
| Number of Participants With ICU Admission | Up to day 90 | Disease severity measured by admission to the ICU |
| Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients | Day 0 to Day28 | Impact of donor antibody titers (high/low) will be assessed by hospitalization rate as measured by number of hospitalizations. |
| 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 |
| Number of Participants With Invasive Mechanical Ventilation | Up to day 90 | Disease severity measured by invasive mechanical ventilation |
| Number of Participants Who Died | Up to day 90 | Disease severity measured by death |
| Number of Participants With Resolved COVID-19 Symptoms at Day 14 | Day 14 | Number of participants with resolved COVID-19 symptoms at day 14 |
| Number of Participants With Resolved COVID-19 Symptoms at Day 28 | Day 28 | Number of participants with resolved COVID-19 symptoms at day 28 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 592 |
| 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.
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. | 589 |
| Total | 1,181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not receive tranfusion | 18 | 26 |
Baseline characteristics
| Characteristic | SARS-CoV-2 Convalescent Plasma | Standard Control Plasma | Total |
|---|---|---|---|
| Age, Continuous | 42 years | 44 years | 43 years |
| Age, Customized 18 - 34 years | 190 Participants | 165 Participants | 355 Participants |
| Age, Customized 35 - 49 years | 207 Participants | 208 Participants | 415 Participants |
| Age, Customized 50 - 64 years | 155 Participants | 176 Participants | 331 Participants |
| Age, Customized >=65 years | 40 Participants | 40 Participants | 80 Participants |
| Asthma No | 533 Participants | 516 Participants | 1049 Participants |
| Asthma Yes | 59 Participants | 73 Participants | 132 Participants |
| BMI category 1 <30 | 382 Participants | 355 Participants | 737 Participants |
| BMI category 1 >=30 | 210 Participants | 234 Participants | 444 Participants |
| BMI category 2 <35 | 495 Participants | 482 Participants | 977 Participants |
| BMI category 2 >=35 | 97 Participants | 107 Participants | 204 Participants |
| Diabetes No | 543 Participants | 539 Participants | 1082 Participants |
| Diabetes Yes | 49 Participants | 50 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 80 Participants | 90 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 512 Participants | 499 Participants | 1011 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HIV infection No | 579 Participants | 577 Participants | 1156 Participants |
| HIV infection Yes | 13 Participants | 12 Participants | 25 Participants |
| Hypertension No | 452 Participants | 453 Participants | 905 Participants |
| Hypertension Yes | 140 Participants | 136 Participants | 276 Participants |
| Pregnant No | 590 Participants | 588 Participants | 1178 Participants |
| Pregnant Yes | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 9 Participants | 17 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 22 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 92 Participants | 71 Participants | 163 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 10 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 459 Participants | 475 Participants | 934 Participants |
| Sex: Female, Male Female | 323 Participants | 352 Participants | 675 Participants |
| Sex: Female, Male Male | 269 Participants | 237 Participants | 506 Participants |
| Time from symptom onset to transfusion | 6 days | 6 days | 6 days |
| Vaccine status Fully vaccinated | 79 Participants | 79 Participants | 158 Participants |
| Vaccine status Partially vaccinated | 27 Participants | 31 Participants | 58 Participants |
| Vaccine status Unvaccinated | 486 Participants | 479 Participants | 965 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 592 | 3 / 589 |
| other Total, other adverse events | 106 / 592 | 109 / 589 |
| serious Total, serious adverse events | 34 / 592 | 55 / 589 |
Outcome results
Primary
Cumulative Incidence of Severe Infusion Reactions
Cumulative incidence measured as rate per person-years experiencing treatment-related severe infusion reactions during the study period.
Time frame: Up to day 28
Population: Includes patients who were randomized and received transfusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Cumulative Incidence of Severe Infusion Reactions | 0.05 Rate per person-years |
| Standard Control Plasma | Cumulative Incidence of Severe Infusion Reactions | 0.00 Rate per person-years |
p-value: 0.1695% CI: [-0.11, 0.02]Rate per person-years
Primary
Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS)
Cumulative incidence measured as rate per person-years of treatment-related severe Acute Respiratory Distress Syndrome (ARDS) during the study period.
Time frame: Up to day 28
Population: Includes patients who were randomized and received transfusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS) | 0.00 Rate per person-years |
| Standard Control Plasma | Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS) | 0.01 Rate per person-years |
p-value: 0.3295% CI: [-0.01, 0.02]Rate per person-years
Primary
Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events
Cumulative incidence measured as rate per person-years experiencing a Grade 3 or higher.
Time frame: Up to day 90
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events | 0.25 Rate per person-years |
| Standard Control Plasma | Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events | 0.43 Rate per person-years |
p-value: 0.0295% CI: [0.03, 0.32]Rate per person-years
Primary
Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization
Cumulative Number measured as the proportion of subjects who were hospitalized or who died prior to hospitalization
Time frame: Up to day 28
Population: Includes patients who were randomized and received transfusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization | 17 Participants |
| Standard Control Plasma | Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization | 37 Participants |
p-value: 0.00595% CI: [1, 5.8]Fisher Exact
Secondary
Serum SARS-CoV-2 Antibody Titers by Visit
Geometric mean Spike Receptor Binding Domain (RBD) titers at day 0, 14, 28 and 90 between the randomized arms.
Time frame: Days 0, 14, 28 and 90
Population: Analysis limited to those that were transfused and had the titer data performed
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Pre-transfusion | 345 Spike Receptor Binding Domain Titer |
| SARS-CoV-2 Convalescent Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Day 14 | 8595 Spike Receptor Binding Domain Titer |
| SARS-CoV-2 Convalescent Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Day 28 | 10980 Spike Receptor Binding Domain Titer |
| SARS-CoV-2 Convalescent Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Day 90 | 13958 Spike Receptor Binding Domain Titer |
| Standard Control Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Day 90 | 13281 Spike Receptor Binding Domain Titer |
| Standard Control Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Pre-transfusion | 316 Spike Receptor Binding Domain Titer |
| Standard Control Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Day 28 | 12241 Spike Receptor Binding Domain Titer |
| Standard Control Plasma | Serum SARS-CoV-2 Antibody Titers by Visit | Day 14 | 9868 Spike Receptor Binding Domain Titer |
Other Pre-specified
Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate
Assess change in hospitalization rate as measured by number of hospitalizations stratified by age groups \<65 and \>=65
Time frame: Day 0 to Day 90
Population: Includes patients who were randomized and received transfusion
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group < 65 | Primary event of hospitalization | 12 Participants |
| SARS-CoV-2 Convalescent Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group < 65 | No primary event of hospitalization | 540 Participants |
| SARS-CoV-2 Convalescent Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group >= 65 | Primary event of hospitalization | 5 Participants |
| SARS-CoV-2 Convalescent Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group >= 65 | No primary event of hospitalization | 35 Participants |
| Standard Control Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group >= 65 | No primary event of hospitalization | 32 Participants |
| Standard Control Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group < 65 | Primary event of hospitalization | 29 Participants |
| Standard Control Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group >= 65 | Primary event of hospitalization | 8 Participants |
| Standard Control Plasma | Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate | Age group < 65 | No primary event of hospitalization | 520 Participants |
Other Pre-specified
Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients
Impact of donor antibody titers (high/low) will be assessed by hospitalization rate as measured by number of hospitalizations.
Time frame: Day 0 to Day28
Population: Analysis limited to those that had the donor titer measured
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients | Hospitalized | 6 Participants |
| SARS-CoV-2 Convalescent Plasma | Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients | Not hospitalized | 296 Participants |
| Standard Control Plasma | Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients | Hospitalized | 10 Participants |
| Standard Control Plasma | Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients | Not hospitalized | 254 Participants |
95% CI: [0.192, 1.425]
Other Pre-specified
Number of Participants Who Died
Disease severity measured by death
Time frame: Up to day 90
Population: Includes patients who were randomized and received transfusion
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Number of Participants Who Died | Deaths | 0 Participants |
| SARS-CoV-2 Convalescent Plasma | Number of Participants Who Died | No deaths | 592 Participants |
| Standard Control Plasma | Number of Participants Who Died | Deaths | 3 Participants |
| Standard Control Plasma | Number of Participants Who Died | No deaths | 586 Participants |
Other Pre-specified
Number of Participants With ICU Admission
Disease severity measured by admission to the ICU
Time frame: Up to day 90
Population: Includes patients who were randomized and received transfusion
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Number of Participants With ICU Admission | Admission to ICU | 3 Participants |
| SARS-CoV-2 Convalescent Plasma | Number of Participants With ICU Admission | No admission to ICU | 589 Participants |
| Standard Control Plasma | Number of Participants With ICU Admission | Admission to ICU | 7 Participants |
| Standard Control Plasma | Number of Participants With ICU Admission | No admission to ICU | 582 Participants |
Other Pre-specified
Number of Participants With Invasive Mechanical Ventilation
Disease severity measured by invasive mechanical ventilation
Time frame: Up to day 90
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Number of Participants With Invasive Mechanical Ventilation | On invasive mechanical ventilation | 0 Participants |
| SARS-CoV-2 Convalescent Plasma | Number of Participants With Invasive Mechanical Ventilation | No invasive mechanical ventilation | 592 Participants |
| Standard Control Plasma | Number of Participants With Invasive Mechanical Ventilation | On invasive mechanical ventilation | 3 Participants |
| Standard Control Plasma | Number of Participants With Invasive Mechanical Ventilation | No invasive mechanical ventilation | 586 Participants |
Other Pre-specified
Number of Participants With Resolved COVID-19 Symptoms at Day 14
Number of participants with resolved COVID-19 symptoms at day 14
Time frame: Day 14
Population: All participants who were transfused and had symptom data for day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Number of Participants With Resolved COVID-19 Symptoms at Day 14 | 146 Participants |
| Standard Control Plasma | Number of Participants With Resolved COVID-19 Symptoms at Day 14 | 134 Participants |
p-value: 0.65Fisher Exact
Other Pre-specified
Number of Participants With Resolved COVID-19 Symptoms at Day 28
Number of participants with resolved COVID-19 symptoms at day 28
Time frame: Day 28
Population: All participants who were transfused and had symptom data for day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Number of Participants With Resolved COVID-19 Symptoms at Day 28 | 250 Participants |
| Standard Control Plasma | Number of Participants With Resolved COVID-19 Symptoms at Day 28 | 245 Participants |
Other Pre-specified
Number of Participants With Resolved COVID-19 Symptoms at Day 90
Number of participants with resolved COVID-19 symptoms at day 90
Time frame: Day 90
Population: All participants who were transfused and had symptom data for day 90
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SARS-CoV-2 Convalescent Plasma | Number of Participants With Resolved COVID-19 Symptoms at Day 90 | 359 Participants |
| Standard Control Plasma | Number of Participants With Resolved COVID-19 Symptoms at Day 90 | 347 Participants |