SARS-CoV-2 Infection
Conditions
Keywords
convalescent, COVID-19, Coronavirus, plasma
Brief summary
The purpose of this study is to evaluate the safety of administration of plasma containing antibodies to the SARS-CoV-2 virus (i.e., convalescent plasma) and if it is able to prevent disease or lessen the severity of disease in individuals who are at high risk of developing COVID-19 due to a recent exposure. This study will also measure the level of anti-SARS-CoV-2 antibodies in patient's blood after the administration of the convalescent plasma.
Detailed description
People who become infected with a virus such as SARS-CoV-2 usually develop an immune response and produce antibodies against the virus. Antibodies are natural proteins made by the body's immune system that attack viruses and other germs. These antibodies are found in plasma, which is the yellow, clear part of the blood. There have been other studies using plasma to treat other types of viruses that showed some positive results. Human plasma containing antibodies to the SARS-CoV-2 virus is an option for prevention and treatment of COVID-19. This type of treatment, known as passive antibody therapy, could be rapidly available when there are sufficient numbers of people who have recovered from infection and can donate antibody-containing plasma. In contrast to vaccination strategies, which begin to provide protection weeks after administration, antibody-containing plasma would provide its protective benefits immediately. Additionally, passive antibody therapy may be the only way to provide immunity for some immunocompromised patients who do not respond to vaccines. This research will evaluate the safety of administration of plasma containing antibodies to the SARS-CoV-2 virus (i.e., convalescent plasma). The research will also measure the level of anti-SARS-CoV-2 antibodies in patient's blood after the administration of the convalescent plasma.
Interventions
1-2 unit (200-250 mL per unit) of plasma with anti-SARS-CoV-19 titers of ≥1:320. The total volume (mL) infused will be based on weight (5 mL/kg) with a maximum volume of 500 mL.
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Between 1 month and 18 years of age at the time of consent. * Determined to be at high-risk for severe SARS-CoV-2 disease based on the American Academy of Pediatrics definition of immunocompromised children and reported high-risk Pediatric subpopulations. These include the following groups: Immunocompromised, Hemodynamically significant cardiac disease {e.g. congenital heart disease}, Lung disease with chronic respiratory failure, Medically complex children defined as children who have a long-term dependence on technological support (including tracheotomy) associated with developmental delay and/or genetic anomalies21, Obesity, Infant, i.e. child ≤1 year old. * Confirmed SARS-CoV-2 infection OR high-risk exposure as defined: 1. Confirmed infection: Child who tested positive for COVID-19 and is no more than 168 hours after onset of symptoms (and within 192 hours at the time of receipt of plasma). 2. High-risk exposure: Susceptible child who was not previously infected or otherwise immune to SARS-CoV-2 and exposed within 96 hours prior to enrollment (and within 120 hours at the time of receipt of plasma). Both criteria below should be met: A household member or daycare center (same room) exposure to a person with \[confirmed SARS-CoV-2 OR with clinically compatible disease in regions with widespread ongoing transmission\] and a negative for SARS-CoV-2 (nasopharyngeal swab) * Subject is judged by the investigator to have the initiative and means to be compliant with the protocol. * Subjects or their legal representatives must have the ability to read, understand, and provide written informed consent for the initiation of any study related procedures.
Exclusion criteria
* History of severe reactions (e.g. anaphylaxis) to transfusion of blood products. Subjects with minor reactions such as fever, itching, chills, etc. that resolve spontaneously or respond to pre-medications, and that do not represent more significant allergic reactions will not be excluded. * Inability to complete therapy with the study product within the stipulated time frame outlined above * Female subjects in child-bearing age with a positive pregnancy test, breastfeeding, or planning to become pregnant/breastfeed during the study period. * Subject / caregiver deemed by the study team to be non-compliant with the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Treatment With High-titer Anti-SARS-CoV-2 Plasma as Assessed by Adverse Events | 28 days | Number of subjects with grade 3 and 4 adverse events during the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Disease Worsening Event | 28 days | Disease worsening as defined by hospitalization, need for supplemental oxygenation, respiratory distress, requirement for mechanical ventilation, and death. |
| Pharmacokinetics of Anti-SARS-CoV-2 Antibodies as Defined by Changes in Antibody Titers | 30 minutes | Anti-SARS-CoV-2 antibody titer changes. Recipient titers 30 minutes after plasma. |
| Pharmacokinetics of Anti-SARS-CoV-2 Antibodies as Defined by Changes in Antibody Titers Over Time | at 30 minutes, 7 days, 14 days, 21 days, 28 days after plasma administration. | Half lives based on totality of data |
| Number of Subjects With a Natural Antibody Response to SARS-CoV-2 Infection | up to 2 months | Presence or absence of endogenous anti-SARS-CoV-2 antibody titers. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anti- SARS-CoV-2 Plasma Human Convalescent Plasma
Anti-SARS-CoV-2 Human Convalescent Plasma: 1-2 unit (200-250 mL per unit) of plasma with anti-SARS-CoV-19 titers of ≥1:320.
The total volume (mL) infused will be based on weight (5 mL/kg) with a maximum volume of 500 mL. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participants was withdrawn from study due to false positive COVID-19 test | 1 |
Baseline characteristics
| Characteristic | Anti- SARS-CoV-2 Plasma |
|---|---|
| Age, Continuous | 7.5 years |
| COVID-19 Signs & Symptoms Asymptomatic | 3 Participants |
| COVID-19 Signs & Symptoms Congestion | 2 Participants |
| COVID-19 Signs & Symptoms Cough | 5 Participants |
| COVID-19 Signs & Symptoms Desaturation | 1 Participants |
| COVID-19 Signs & Symptoms Fever | 8 Participants |
| COVID-19 Signs & Symptoms Headache | 1 Participants |
| COVID-19 Signs & Symptoms Muscle Aches | 1 Participants |
| COVID-19 Signs & Symptoms Respiratory failure requiring noninvasive ventilation | 3 Participants |
| COVID-19 Signs & Symptoms Sore throat | 2 Participants |
| COVID-19 Signs & Symptoms Tachypnea | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Hospital Admission No | 8 Participants |
| Hospital Admission Yes | 6 Participants |
| Previous diagnosis Asthma | 1 Participants |
| Previous diagnosis Ataxia Telangiectasia, chronic lung disease | 1 Participants |
| Previous diagnosis Ataxia telangiectasia, IVIG dependent | 1 Participants |
| Previous diagnosis Caroli syndrome, ARPKD, liver and kidney transplant, tracheostomy | 1 Participants |
| Previous diagnosis Cerebral palsy, epilepsy, chronic lung disease | 1 Participants |
| Previous diagnosis Chromosome 18q deletion, CVID, IVIG dependent, chronic lung disease | 1 Participants |
| Previous diagnosis Crohn's disease, receiving infliximab | 1 Participants |
| Previous diagnosis DICER1-associated parietal lobe sarcoma | 1 Participants |
| Previous diagnosis Immunodeficiency with CARD11 mutation and IVIG dependent | 1 Participants |
| Previous diagnosis Liver failure | 1 Participants |
| Previous diagnosis Prematurity, acyanotic Tetralogy of Fallot, chronic lung disease | 1 Participants |
| Previous diagnosis Prematurity, chronic lung disease, CVID, IVIG dependent | 1 Participants |
| Previous diagnosis SMA type 1 | 1 Participants |
| Previous diagnosis S/P Wilms tumor and BMT asthma | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 14 Participants |
| SARS CoV-2 PCR False Positive SARS CoV-2 PCR | 1 Participants |
| SARS CoV-2 PCR Negative SARS CoV-2 PCR | 5 Participants |
| SARS CoV-2 PCR Positive SARS CoV-2 PCR | 8 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 3 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Safety of Treatment With High-titer Anti-SARS-CoV-2 Plasma as Assessed by Adverse Events
Number of subjects with grade 3 and 4 adverse events during the study period.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anti- SARS-CoV-2 Plasma | Safety of Treatment With High-titer Anti-SARS-CoV-2 Plasma as Assessed by Adverse Events | 0 Participants |
Secondary
Number of Subjects With a Natural Antibody Response to SARS-CoV-2 Infection
Presence or absence of endogenous anti-SARS-CoV-2 antibody titers.
Time frame: up to 2 months
Population: SARS-CoV-2-infected participants who demonstrated presence of endogenous antibody production
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anti- SARS-CoV-2 Plasma | Number of Subjects With a Natural Antibody Response to SARS-CoV-2 Infection | 7 Participants |
Secondary
Number of Subjects With Disease Worsening Event
Disease worsening as defined by hospitalization, need for supplemental oxygenation, respiratory distress, requirement for mechanical ventilation, and death.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anti- SARS-CoV-2 Plasma | Number of Subjects With Disease Worsening Event | 0 Participants |
Secondary
Pharmacokinetics of Anti-SARS-CoV-2 Antibodies as Defined by Changes in Antibody Titers
Anti-SARS-CoV-2 antibody titer changes. Recipient titers 30 minutes after plasma.
Time frame: 30 minutes
Population: Recipient titers 30 minutes after plasma administration was available for 9 participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Anti- SARS-CoV-2 Plasma | Pharmacokinetics of Anti-SARS-CoV-2 Antibodies as Defined by Changes in Antibody Titers | 5.6 percent of donor titer |
Secondary
Pharmacokinetics of Anti-SARS-CoV-2 Antibodies as Defined by Changes in Antibody Titers Over Time
Half lives based on totality of data
Time frame: at 30 minutes, 7 days, 14 days, 21 days, 28 days after plasma administration.
Population: Calculation of antibody half-lives (T1/2) was available for 7 participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Anti- SARS-CoV-2 Plasma | Pharmacokinetics of Anti-SARS-CoV-2 Antibodies as Defined by Changes in Antibody Titers Over Time | 15.1 Antibody half lives (days) |