COVID-19
Conditions
Keywords
Coronavirus, Covid19, SARS-CoV-2
Brief summary
* This is a phase II randomized study of convalescent plasma for the treatment of non-immune individuals with COVID-19 infection at high risk of complications. * Subjects will be considered as having completed the study after 2 months (+/- 5) days, unless consent withdrawal or death occurs first. * Subjects will be randomized to receiving convalescent plasma or best supportive care. * Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease. * The final analysis will be conducted once the last subject completes the 2-month visit or withdraws from the study.
Detailed description
Overall study design * This is a phase II randomized study of convalescent plasma for the treatment of non-immune individuals with COVID-19 infection at high risk of complications. * Subjects will be considered as having completed the study after 2 months (+/- 5) days, unless consent withdrawal or death occurs first. * Subjects will be randomized to receiving convalescent plasma or best supportive care. * Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease. * The final analysis will be conducted once the last subject completes the 2-month visit or withdraws from the study. A total of 306 subjects will be recruited, 153 for each arm. If a patient in the best supportive care arm requires hospitalization, the patient will be eligible to receive convalescent plasma if requested and/or deemed medically appropriate by the admitting physician. Overall study duration * The study begins when the first subject (donor or recipient) signs the informed consent. The study will end once the last enrolled subject completes the study (likely a recipient). * The expected duration of the study is approximately 12 months.
Interventions
BIOLOGICALConvalescent Plasma
Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection
OTHERBest Supportive Care
Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.
Sponsors
United States Department of Defense
Hackensack Meridian Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Donor Eligibility Criteria: * Age 18-60 * A history of a positive nasopharyngeal swab for COVID-19 or a history of positive antibody titer test. * At least 14 days from resolution of COVID-19-associated symptoms including fevers. * A negative nasopharyngeal swab (or similar test) for COVID-19 * anti-SARS-CoV2 titers \>1:500 * Adequate venous access for apheresis * Meets donor eligibility criteria in accordance to Hackensack University Medical Center (HUMC) Collection Facility at the John Theurer Cancer Center (JTCC) if collecting at the JTCC, and all regulatory agencies as describes in SOP 800 01. * Required testing of the donor and product must be performed in accordance to FDA regulations (21 CFR 610.40), and the donation must be found suitable (21 CFR 630.30) Recipient Eligibility Criteria: * Patient age \>30 years old, newly diagnosed with a COVID-19 infection with onset of first symptoms \< 96 hours. * And least one other high-risk feature: 1. Age \> 65 2. BMI 30 or above 3. Hypertension, defined as SBP above 140 or DBP above 90, or requiring medication for control. 4. Coronary artery disease (history, not ECG changes only) 5. Congestive heart failure 6. Peripheral vascular disease (includes aortic aneurysm \>= 6 cm) 7. Cerebrovascular disease (history of CVA or TIA) 8. Dementia 9. Chronic pulmonary disease 10. Liver disease (such as portal hypertension, chronic hepatitis) 11. Diabetes (excludes diet-controlled alone) 12. Moderate or severe renal disease defined as having a GFR \< 60 mL/min 13. Cancer (exclude if \> 5 year in remission) 14. AIDS (not just HIV positive) Recipient
Exclusion criteria
* History of severe transfusion reaction to plasma products * Need for oxygen supplementation * Positive test for COVID-19 antibodies * Chemotherapy-induced neutropenia (ANC \< 0.5 x 103/mcL) * Immunosuppressive medications except for prednisone (or steroid equivalent) \> 10 mg daily. * Performance status \< 50 by KPS * Pneumonia by radiographic evaluation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization Rate | 10 Days | The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Donor Titers Level on Efficacy | 2 Months | — |
| Rate of Nasopharyngeal Swab Positivity in Donors | 2 Months | — |
| Time to Symptoms Resolution | 2 Months | The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date. |
| Rate of Donor Titers Level | 2 Months | Rate of Donor Titer Levels \>1:1000 |
| Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks | 2 Weeks | — |
| Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months. | Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months | — |
| Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks | 4 Weeks | — |
| Overall Survival Rate | 2 Months | Overall survival (OS) will be defined as Rate of death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization | 2 Weeks and 4 Weeks | — |
| Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization | 2 Weeks and 4 Weeks | — |
| Rates of Adverse Events Associated With Convalescent Plasma Infusion. | Day 3 and 7, Weeks 2 and 4 | Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days). |
| Plasma Product's Procalcitonin (PCT) Level Assessment | Day 0 | — |
| Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment | Day 0 | — |
| Plasma Product's Annexin V Level Assessment | Day 0 | — |
| Plasma Product's Surfactant Protein D (SP-D) Level Assessment | Day 0 | — |
| Plasma Product's microRNA Level Assessment | Day 0 | — |
| Plasma Product's Cytokine Level Assessment | Day 0 | Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data. |
| Plasma Product's Mannose-binding Lectin (MBL) Level Assessment | Day 0 | — |
| Plasma Product's C-reactive Protein (CRP) Level Assessment | Day 0 | — |
| Plasma Product's Immunoglobulin Level Assessment | Day 0 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Convalescent Plasma Fresh or frozen plasma will be infused one time to patients
Convalescent Plasma: Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection | 10 |
| Best Supportive Care Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.
Best Supportive Care: Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease. | 11 |
| Total | 21 |
Baseline characteristics
| Characteristic | Convalescent Plasma | Best Supportive Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 11 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) White | 9 Participants | 7 Participants | 16 Participants |
| Region of Enrollment United States | 10 participants | 11 participants | 21 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 1 / 10 | 0 / 11 |
| serious Total, serious adverse events | 1 / 10 | 3 / 11 |
Outcome results
Primary
Hospitalization Rate
The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.
Time frame: 10 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Hospitalization Rate | 1 Participants |
| Best Supportive Care | Hospitalization Rate | 3 Participants |
Secondary
Impact of Donor Titers Level on Efficacy
Time frame: 2 Months
Population: Due to a lack of funding and early termination of the trial, these data were not collected.
Secondary
Overall Survival Rate
Overall survival (OS) will be defined as Rate of death
Time frame: 2 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Convalescent Plasma | Overall Survival Rate | 0 Patient Deaths |
| Best Supportive Care | Overall Survival Rate | 0 Patient Deaths |
Secondary
Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.
Time frame: Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months
Population: Due to a lack of funding and early termination of the trial, these data were not collected.
Secondary
Rate of Donor Titers Level
Rate of Donor Titer Levels \>1:1000
Time frame: 2 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Rate of Donor Titers Level | 55 Participants |
Secondary
Rate of Nasopharyngeal Swab Positivity in Donors
Time frame: 2 Months
Population: Due to a lack of funding and early termination of the trial, these data were not collected.
Secondary
Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks
Time frame: 2 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks | 6 Participants |
| Best Supportive Care | Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks | 6 Participants |
Secondary
Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks
Time frame: 4 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks | 5 Participants |
| Best Supportive Care | Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks | 2 Participants |
Secondary
Time to Symptoms Resolution
The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.
Time frame: 2 Months
Population: Due to a lack of funding and early termination of the trial, these data were not collected.
Other Pre-specified
Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization
Time frame: 2 Weeks and 4 Weeks
Other Pre-specified
Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization
Time frame: 2 Weeks and 4 Weeks
Other Pre-specified
Plasma Product's Annexin V Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's C-reactive Protein (CRP) Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's Cytokine Level Assessment
Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data.
Time frame: Day 0
Other Pre-specified
Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's Immunoglobulin Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's Mannose-binding Lectin (MBL) Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's microRNA Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's Procalcitonin (PCT) Level Assessment
Time frame: Day 0
Other Pre-specified
Plasma Product's Surfactant Protein D (SP-D) Level Assessment
Time frame: Day 0
Other Pre-specified
Rates of Adverse Events Associated With Convalescent Plasma Infusion.
Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days).
Time frame: Day 3 and 7, Weeks 2 and 4