COVID-19
Conditions
Keywords
COVID-19, Coronavirus, Infection, SARS-CoV-2, Randomized, Hospitalized, Plasma, Neutralizing, Antibody
Brief summary
The purpose of this research study is to find out if CCP is safe and to determine the safest and most effective level of anti-viral antibody when given to people admitted to the hospital with confirmed COVID-19 infection. Participants enrolled on this study will be transfused with 2 units of CCP through an IV. These units will be given one at a time 4 to 24 hours apart. Participants will be randomized to receive either 2 units with standard antibody levels as recommended by the FDA or 2 units with an antibody level higher than that recommended by the FDA. This study is experimental and CCP is investigational and has not been approved by the FDA for the treatment of COVID-19. The CCP is collected per FDA guidelines from persons recovered from COVID-19 infection. The plasma contains antibodies and possibly other properties that inhibit the virus. The investigators do not know if the level of antibodies present in the CCP will make a difference in how the participant's body is able to fight the infection and hope to learn that in this study.
Detailed description
This randomized, double-blinded, phase 2 trial will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with less than 8 days of symptoms. Eligible participants will receive institutional-guided standard-of-care (SOC) and ABO-compatible convalescent COVID-19 plasma (CCP). The CCP units will be tested for the presence of anti-SARS-CoV-2 antibodies and pre-assigned as high-titer (CCP1) or standard-titer (CCP2) in a 1:1 randomization. Participants and clinical investigators will be blinded to the CCP titer group identities. The investigators plan to enroll approximately 56 participants (28 in each group) at UNC-Chapel Hill. Participants will be randomized within 48 hours of admission to a COVID service and will receive convalescent plasma within 24 hours of randomization. At least two units of CCP will be transfused 4-24 hours apart on study Day 0. If available, a third unit may be administered. All participants will undergo a series of safety and efficacy assessments pre-, during, and post-transfusion. Samples for research will be collected on Day 0 through Day 28, unless previously discharged. Additionally, after discharge, participants can provide longitudinal samples collected at 1, 3, and 6-month timepoints after the infusion.
Interventions
BIOLOGICALHigh-titer Convalescent COVID-19 Plasma (CCP1)
At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
BIOLOGICALStandard-titer Convalescent COVID-19 plasma (CCP2)
At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study is double-blinded so neither the participant nor the study team/investigators will know which plasma treatment (CCP1 or CCP2) that the participant is receiving.
Intervention model description
This study has 2 treatment arms and participants will be assigned/randomized to one arm: 1. CCP1 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned high-titer 2. CCP2 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned standard-titer
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age at least 18 years 2. Ability and willingness of participant or Legally Authorized Representative (LAR) to give written informed consent. 3. Laboratory confirmed diagnosis of infection with SARS-CoV-2 by PCR 4. Hospitalized for COVID-19 with one or more respiratory or gastrointestinal (GI) symptoms: * COVID-19 associated respiratory symptoms include but are not limited to: cough, shortness of breath, difficulty breathing, or sore throat * COVID-19 associated GI symptoms include but are not limited to: loss of taste, loss of sense of smell, diarrhea, nausea, or vomiting, Note: Respiratory and GI symptoms other than those listed above, must be noted as acceptable and signed by study PI or designee.
Exclusion criteria
1. Receipt of pooled immunoglobulin in past 30 days 2. Current or prior enrollment in a SARS-CoV-2 antibody or T-cell therapeutic study. Note: Patients enrolled on other randomized controlled trials of pharmaceutical and/or non-pharmaceutical interventions for COVID and meeting eligibility criteria will not be excluded, as determined by study PI (or designee) on a case-by-case basis and as allowed by eligibility criteria of the other trials. 3. Contraindication to transfusion or history of prior reactions to transfusion blood products. This may include religious or cultural objections to receiving blood products and transfusions. 4. ABO-compatible titered plasma is not available 5. \> 10 days from noted COVID-related subjective or objective fever at randomization. Patients without subjective or objective fever, \> 10 days from symptom onset as determined by study PI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Serious Adverse Events (SAE) Through Study Day 14 | 14 days | Total number of SAE among all participants through Day 14; Definition of SAE per protocol and will only be included if related to COVID-19 Convalescent Plasma (CCP): 1. Death; 2. Life-threatening (immediate risk of death); 3. Prolongation of existing hospitalization; 4. Persistent or significant disability or incapacity; OR 5. Important medical events that may not result in death, be life threatening, or require intervention or escalation of care may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, or convulsions that do not result in inpatient hospitalization. |
| Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP | up to 28 days | Median number of days to hospital discharge following first dose of CCP among all participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Titer (CCP1) Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment.
High-titer Convalescent COVID-19 Plasma (CCP1): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available. | 15 |
| Standard-Titer (CCP2) Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment.
Standard-titer Convalescent COVID-19 plasma (CCP2): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available. | 41 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 10 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 9 |
Baseline characteristics
| Characteristic | High-Titer (CCP1) | Total | Standard-Titer (CCP2) |
|---|---|---|---|
| Age, Continuous | 57 years | 61 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 18 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 37 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 14 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 18 Participants | 13 Participants |
| Race (NIH/OMB) White | 8 Participants | 23 Participants | 15 Participants |
| Region of Enrollment United States | 15 Participants | 56 Participants | 41 Participants |
| Sex: Female, Male Female | 6 Participants | 20 Participants | 14 Participants |
| Sex: Female, Male Male | 9 Participants | 36 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 14 | 10 / 41 |
| other Total, other adverse events | 13 / 14 | 38 / 41 |
| serious Total, serious adverse events | 2 / 14 | 15 / 41 |
Outcome results
Primary
Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP
Median number of days to hospital discharge following first dose of CCP among all participants.
Time frame: up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-Titer (CCP1) | Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP | 5 Days |
| Standard-Titer (CCP2) | Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP | 7 Days |
Primary
Total Number of Serious Adverse Events (SAE) Through Study Day 14
Total number of SAE among all participants through Day 14; Definition of SAE per protocol and will only be included if related to COVID-19 Convalescent Plasma (CCP): 1. Death; 2. Life-threatening (immediate risk of death); 3. Prolongation of existing hospitalization; 4. Persistent or significant disability or incapacity; OR 5. Important medical events that may not result in death, be life threatening, or require intervention or escalation of care may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, or convulsions that do not result in inpatient hospitalization.
Time frame: 14 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High-Titer (CCP1) | Total Number of Serious Adverse Events (SAE) Through Study Day 14 | 0 Serious Adverse Events |
| Standard-Titer (CCP2) | Total Number of Serious Adverse Events (SAE) Through Study Day 14 | 0 Serious Adverse Events |