A Phase 2 interventional study of High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma in Corona Virus Infection, SARS-CoV 2 and SARS Pneumonia, sponsored by University of Virginia. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-01.
Sponsored by University of Virginia · Phase 2, Interventional, and Treatment
This is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.
There are no proven treatments for coronavirus disease (COVID-19) and associated pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent experience in China suggests that convalescent immune plasma(CIP)may be an effective treatment for COVID-19. In the pandemic situation where there are no vaccines for COVID-19, specific antibodies in convalescent plasma induced by infection may provide passive protective immunity. Passive antibody therapy was the first immunotherapy dating back to the 1890's for the treatment of infectious diseases before the development of antibiotics 1940's. Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1 shows that such convalescent plasma contains neutralizing antibodies to the relevant virus. In SARS-CoV-2, passive antibody therapy from CIP probably provided protection by viral neutralization. CIP was also used in the 2013 Ebola epidemic. A small non-randomized study in Sierra Leone revealed a significant increase in survival for who received CIP4. CIP administration is the only approach that provides immediate immunity to patients who have been exposed or who have active disease.
This approach is immediately available from individuals who have recovered, are viral free,and can donate immune plasma (IP) containing high titer neutralizing antibodies. Passive antibody therapy can be given to a patient recently exposed or a patient who is developing an infection with COVID-19 by obtaining plasma units from immune individuals by standard plasmapheresis using FDA-approved blood banking procedures, cross matching the unit(s) to the recipients and infusing the unit(s) using standard transfusion procedures for blood products. Based on the safety and long-term experience with plasma infusions, plasma exchanges, and other procedures involving plasma or plasma product, this protocol was designed as a phase II single arm trial that involves the administration of antibodies to a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent.
The only antibody formulation that is available for emergent use is that found in convalescent plasma. As more individuals contract COVID-19 and recover, the number of potential donors will increase.
The principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculum, which is likely to be much smaller than that of established disease. Alternatively, antibodies may dampen the early inflammatory response leaving the infected individual asymptomatic. For example, antibody therapy for pneumococcal pneumonia was most effective when given shortly after the onset of symptoms and was of no benefit if antibody therapy was delayed beyond the third day of disease. For passive antibody therapy to be effective, a sufficient amount of antibody must be infused. The antibody will circulate in the blood, reach tissues,and provide protection against infection. Depending on the type of antibody, amount, and composition, the half-life can vary from weeks to months. It is under these circumstances, the investigators plan to treat patients who are sick enough to be hospitalized before the onset of overwhelming disease involving a systemic inflammatory response, sepsis, and/or ARDS.
6,687 studies on the registry are indexed under Infections; 807 are open to participants now.
This study's enrollment of 29 is below the median of 120 across 4,200 interventional studies indexed under Infections.
Browse Infections studies →University of Virginia is the lead sponsor of 653 studies on the registry; 134 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 41 (68%) have results posted.
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Exclusion Criteria:
A total of 29 eligible subjects will be enrolled to receive high titer anti-SARS-CoV-2 plasma. Participants will be compared to a historical control group via retrospective chart review.
Drug: High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma
Pathogen reduced SARS-CoV-2 convalescent plasma (1-2 units; \~200 mL each for a total of 200-400mls) given preferably in one day, but allowable to be given over 2 days if clinical circumstances delay infusions in 1 day), with titer to be determined after the unit has been infused.
Number of Participants Transferred to Intensive Care Unit (ICU)
Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.
Time frame: Days 0 - 60
28 Day Mortality
Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.
Time frame: Days 0 - 28
Number of Participants With Serious Adverse Events
Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.
Time frame: Days 0 - 60
Duration of SARS-CoV-2 Positivity
Respiratory tract swabs will be collected on days, 0, 7, 14, and 21 and will be tested for SARS-CoV-2. The outcome measurement is determining the duration from date of infection until date of first documented negative PCR test, which was assed up to 21 days
Time frame: Days 0 - 21
Serum of Plasma Antibody Titer to SARS-CoV-2
Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.
Time frame: Day 28
Cellular and Humoral Immune Response
Blood will be collected and analyzed for for Spike IgG levels.
Time frame: Day 28
Supplemental Oxygen Free Days
All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.
Time frame: Days 0-28
Ventilator Free Days
All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.
Time frame: Days 0 - 28
ICU Free Days
All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.
Time frame: Days 0 - 28
Sequential Organ Failure Assessment Score Improvement
Throughout the study, participants were evaluated by study physician using the sequential organ failure assessment score. This outcome measurement is looking for the number of participants who's score improved over the duration of the study.
Time frame: days 0-28
Number of Participants Who Needed for Vasopressors
Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.
Time frame: Days 0 - 60
Number of Participants Who Needed Renal Replacement Therapy
Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.
Time frame: Days 0 - 60
Number of Participants Who Needed Extracorporeal Membrane Oxygenation (ECMO)
Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.
Time frame: Days 0 - 60
Hospital Length of Stay (LOS)
Will be calculated from the date the patient entered the hospital until they were discharged.
Time frame: Days 0-60
ICU LOS
Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.
Time frame: days 0 - 60
Number of Participants Who Had a Grade 3 or 4 Adverse Events (AEs)
All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.
Time frame: Adverse events were collected from day 0 to 7 days post infusion.
| Milestone | Study Participants |
|---|---|
| Started | 29 |
| Completed | 29 |
| Not completed | 0 |
Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.
| Participants | Study Participants |
|---|---|
| Number of Participants Transferred to Intensive Care Unit (ICU) | 4 |
Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.
| Participants | Study Participants |
|---|---|
| 28 Day Mortality | 2 |
Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.
| Participants | Study Participants |
|---|---|
| Number of Participants With Serious Adverse Events | 4 |
Respiratory tract swabs will be collected on days, 0, 7, 14, and 21 and will be tested for SARS-CoV-2. The outcome measurement is determining the duration from date of infection until date of first documented negative PCR test, which was assed up to 21 days
| days | Study Participants |
|---|---|
| Duration of SARS-CoV-2 Positivity | 20.4 ± 1.57 |
Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.
| ug/mL | Study Participants |
|---|---|
| Serum of Plasma Antibody Titer to SARS-CoV-2 | 7.7 (0.1 to 112.1) |
Blood will be collected and analyzed for for Spike IgG levels.
| ug/mL | Study Participants |
|---|---|
| Cellular and Humoral Immune Response | 58.0 (34.0 to 90.0) |
All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.
| Days | Study Participants |
|---|---|
| Supplemental Oxygen Free Days | 23.5 (21 to 26) |
All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.
| days | Study Participants |
|---|---|
| Ventilator Free Days | 24.93 ± 1.46 |
All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.
| days | Study Participants |
|---|---|
| ICU Free Days | 24.59 ± 1.61 |
Throughout the study, participants were evaluated by study physician using the sequential organ failure assessment score. This outcome measurement is looking for the number of participants who's score improved over the duration of the study.
| Participants | Study Participants |
|---|---|
| Sequential Organ Failure Assessment Score Improvement | 27 |
Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.
| Participants | Study Participants |
|---|---|
| Number of Participants Who Needed for Vasopressors | 4 |
Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.
| Participants | Study Participants |
|---|---|
| Number of Participants Who Needed Renal Replacement Therapy | 1 |
Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.
| Participants | Study Participants |
|---|---|
| Number of Participants Who Needed Extracorporeal Membrane Oxygenation (ECMO) | 1 |
Will be calculated from the date the patient entered the hospital until they were discharged.
| days | Study Participants |
|---|---|
| Hospital Length of Stay (LOS) | 9.39 ± 1.56 |
Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.
| days | Study Participants |
|---|---|
| ICU LOS | 2.93 ± 1.72 |
All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.
| Participants | Study Participants |
|---|---|
| Number of Participants Who Had a Grade 3 or 4 Adverse Events (AEs) | 6 |
Collected over Adverse events were collected from day 0 to 7 days post infusion.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Study Participants | 2/29 (6.9%) | 4/29 (13.8%) | 11/29 (37.9%) |
| Event | Study Participants |
|---|---|
| Respiratory FailureRespiratory, thoracic and mediastinal disorders | 3/29 |
| SepsisBlood and lymphatic system disorders | 1/29 |
| Event | Study Participants |
|---|---|
| Pulmonary EdemaRespiratory, thoracic and mediastinal disorders | 5/29 |
| feverInfections and infestations | 3/29 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/29 |
| Hypertension urgencyCardiac disorders | 1/29 |
| hypotensionCardiac disorders | 1/29 |
| syncopeVascular disorders | 1/29 |
| epistaxisGeneral disorders | 1/29 |
| creatine increasedHepatobiliary disorders | 1/29 |
| ALT/AST increasedHepatobiliary disorders | 1/29 |
| atrial fibrillationCardiac disorders | 1/29 |
| Age, Continuous(years) | Study Participants |
|---|---|
| Mean | 57.6 ± 2.5 |
| Sex: Female, Male(Participants) | Study Participants |
|---|---|
| Female | 14 |
| Male | 15 |
| Ethnicity (NIH/OMB)(Participants) | Study Participants |
|---|---|
| Hispanic or Latino | 12 |
| Not Hispanic or Latino | 17 |
| Unknown or Not Reported | 0 |
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