COVID-19
Conditions
Keywords
Coronavirus, Covid19, SARS-CoV-2
Brief summary
* This is a single arm phase IIa study of convalescent plasma for the treatment of individuals hospitalized with COVID-19 infection. * Subjects will be considered as having completed the study after 60 (+/- 3) days, unless consent withdrawal or death occurs first. * Interim analysis will be permitted as described in the statistical section 8. * The final analysis will be conducted once the last subject completes the day 60 visit or withdraws from the study.
Detailed description
Overall study design * This is a single arm phase IIa study of convalescent plasma for the treatment of individuals hospitalized with COVID-19 infection. * Subjects will be considered as having completed the study after 60 (+/- 3) days, unless consent withdrawal or death occurs first. * Interim analysis will be permitted as described in the statistical section 8. * The final analysis will be conducted once the last subject completes the day 60 visit or withdraws from the study. Number of subjects • Up to 36 patients in track 2, and 19 patients in track 3 as described in the statistical section 8. Overall study duration * The study begins when the first subject (this will likely be a donor) 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
Sponsors
Hackensack Meridian Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 titer test. * At least 14 days from resolution of COVID-19-associated symptoms including fevers * One negative nasopharyngeal swabs for COVID-19 RNA * Covid-19 neutralizing antibody \>1:64 * 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 (Appendix A) * 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: Recipients age \>18 years old, are assigned to one of two clinical tracks, track 2 or 3, based on COVID-19 disease severity. Onset of first symptoms \< 9 days. Track 2: * Hospitalized, moderate symptoms requiring medical care for COVID-19 infection * Symptoms may include fever, dyspnea, dehydration among others * Hypoxemia may be present but is not a requirement Track 3: * Requiring mechanical ventilation for the care of COVID-19 infection * Requiring non-invasive positive pressure ventilation (NIPPV), such as continuous airway pressure (CPAP),bi-level positive airway pressure (BiPAP) or high flow nasal canula (HFNC). Recipient
Exclusion criteria
* History of severe transfusion reaction to plasma products * Infusion of immune globulin within the previous 30 days * AST or ALT \> 10 x upper limit of normal * Requirement for vasopressors * COVID-19-associated acute kidney injury requiring dialysis * DNR status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Hospitalized for COVID-19 But Not Intubated | 7 Days | Mechanical ventilation rate at 7 days from starting treatment in hospitalized COVID-19 patients |
| Primary Objective for Patients With COVID-19 Already Intubated | 30 Days | Mortality rate at 30 days from starting treatment for patients with COVID-19 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Hospitalization | 60 Days | The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death. Patients who are not discharged, are alive and still in the hospital on the date of closing follow-up, or lost follow-up on the date of closing follow-up will be considered censored on that date. |
| Time to Symptoms Resolution | 60 Days | The time to symptom resolution is defined as the time in days from new therapy initiation to the first documented symptom resolution as assessed by local site. Patients whose symptom are not resolved, who are dead, or lost follow-up on the designed follow-up date will be censored on that date. |
| Duration of Mechanical Ventilation | 60 Days | The duration of mechanical ventilation is defined as the time in days from the first day of using mechanical ventilation to the last day of using mechanical ventilation. All evaluable patients will be included and no censoring for this analysis. |
| Recipient Anti-SARS-CoV2 Titer Assessment on Days 3 | 3 Days | — |
| Recipient Anti-SARS-CoV2 Titer Assessment on Day 10 | 10 Days | — |
| Recipient Anti-SARS-CoV2 Titer Assessment on Day 30 | 30 Days | — |
| Rate of Virologic Clearance by Nasopharyngeal Swab at Day 10 | 10 Days | — |
| Rate of Virologic Clearance by Nasopharyngeal Swab at Day 30 | 30 Days | — |
| Impact of Donor Titers Level on Efficacy | 60 Days | — |
| Impact of Donor Titers Level on Safety | 60 Days | — |
| Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion) | 0 Days (pre-infusion) | — |
| Overall Survival | 60 Days | Overall survival rate at 60 days from starting treatment for patients with COVID-19 |
| Recipient Anti-SARS-CoV2 Titer Assessment on Day 60 | 60 Days | — |
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 | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 11 |
| Overall Study | Screen Failure | 1 |
Baseline characteristics
| Characteristic | Convalescent Plasma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age, Continuous | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 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 | 30 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 52 |
| other Total, other adverse events | 0 / 52 |
| serious Total, serious adverse events | 24 / 52 |
Outcome results
Primary
Number of Participants Hospitalized for COVID-19 But Not Intubated
Mechanical ventilation rate at 7 days from starting treatment in hospitalized COVID-19 patients
Time frame: 7 Days
Population: Of the 52 participants enrolled, 36 were not intubated at time of enrollment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Number of Participants Hospitalized for COVID-19 But Not Intubated | 5 Participants |
Primary
Primary Objective for Patients With COVID-19 Already Intubated
Mortality rate at 30 days from starting treatment for patients with COVID-19
Time frame: 30 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Primary Objective for Patients With COVID-19 Already Intubated | 7 Participants |
Secondary
Duration of Hospitalization
The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death. Patients who are not discharged, are alive and still in the hospital on the date of closing follow-up, or lost follow-up on the date of closing follow-up will be considered censored on that date.
Time frame: 60 Days
Population: The study was terminated early due to rapid change in standard therapy. This information was not collected or analyzed due to early termination.
Secondary
Duration of Mechanical Ventilation
The duration of mechanical ventilation is defined as the time in days from the first day of using mechanical ventilation to the last day of using mechanical ventilation. All evaluable patients will be included and no censoring for this analysis.
Time frame: 60 Days
Population: The study was terminated early due to rapid change in standard therapy. This information was not collected or analyzed due to early termination.
Secondary
Impact of Donor Titers Level on Efficacy
Time frame: 60 Days
Population: The study was terminated early due to rapid change in standard therapy. This information was not collected or analyzed due to early termination.
Secondary
Impact of Donor Titers Level on Safety
Time frame: 60 Days
Population: The study was terminated early due to rapid change in standard therapy. This information was not collected or analyzed due to early termination.
Secondary
Overall Survival
Overall survival rate at 60 days from starting treatment for patients with COVID-19
Time frame: 60 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Overall Survival | 40 Participants |
Secondary
Rate of Virologic Clearance by Nasopharyngeal Swab at Day 10
Time frame: 10 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Rate of Virologic Clearance by Nasopharyngeal Swab at Day 10 | 7 Participants |
Secondary
Rate of Virologic Clearance by Nasopharyngeal Swab at Day 30
Time frame: 30 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Convalescent Plasma | Rate of Virologic Clearance by Nasopharyngeal Swab at Day 30 | 8 Participants |
Secondary
Recipient Anti-SARS-CoV2 Titer Assessment on Day 10
Time frame: 10 Days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 10 | IgG Levels >=10,000 | 35 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 10 | IgG Levels 1000-10,000 | 7 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 10 | IgG Levels 500-1,000 | 0 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 10 | IgG Levels 100-500 | 4 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 10 | IgG Levels BLQ | 1 Participants |
Secondary
Recipient Anti-SARS-CoV2 Titer Assessment on Day 30
Time frame: 30 Days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 30 | IgG Levels >=10,000 | 29 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 30 | IgG Levels 1000-10,000 | 3 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 30 | IgG Levels 500-1,000 | 0 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 30 | IgG Levels 100-500 | 1 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 30 | IgG Levels BLQ | 0 Participants |
Secondary
Recipient Anti-SARS-CoV2 Titer Assessment on Day 60
Time frame: 60 Days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 60 | IgG Levels >=10,000 | 25 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 60 | IgG Levels 1000-10,000 | 5 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 60 | IgG Levels 500-1,000 | 0 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 60 | IgG Levels 100-500 | 1 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Day 60 | IgG Levels BLQ | 0 Participants |
Secondary
Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion)
Time frame: 0 Days (pre-infusion)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion) | IgG Levels >=10,000 | 8 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion) | IgG Levels 1000-10,000 | 23 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion) | IgG Levels 500-1,000 | 4 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion) | IgG Levels 100-500 | 8 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion) | IgG Levels BLQ | 8 Participants |
Secondary
Recipient Anti-SARS-CoV2 Titer Assessment on Days 3
Time frame: 3 Days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 3 | IgG Levels >=10,000 | 23 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 3 | IgG Levels 1000-10,000 | 16 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 3 | IgG Levels 500-1,000 | 2 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 3 | IgG Levels 100-500 | 6 Participants |
| Convalescent Plasma | Recipient Anti-SARS-CoV2 Titer Assessment on Days 3 | IgG Levels BLQ | 0 Participants |
Secondary
Time to Symptoms Resolution
The time to symptom resolution is defined as the time in days from new therapy initiation to the first documented symptom resolution as assessed by local site. Patients whose symptom are not resolved, who are dead, or lost follow-up on the designed follow-up date will be censored on that date.
Time frame: 60 Days
Population: Due to the early termination of the trial, data regarding this outcome were not collected.