COVID-19 Convalescent Plasma for Mechanically Ventilated Population

Study Overview
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Brief Summary
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The purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it can improve patients' health when they are sick with COVID-19.

Detailed Description
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This open-label, single arm, phase 1 trial will assess the safety and efficacy of convalescent plasma in severely ill, mechanically ventilated participants with pneumonia due to COVID-19. This study will enroll adults 18 years old and older, including pregnant women. A total of 50 eligible participants will receive 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19. Participants will receive convalescent plasma on Study Day 1 in addition to standard of care. Participants will be assessed daily while hospitalized and then on Study Days 15, 22, 29, and 60. All participants will undergo a series of safety, efficacy, and laboratory assessments. Blood samples will be collected on Days 1 (prior to plasma administration), 3, 5, 8, 11, 15, 29, and 60. Oropharyngeal or endotracheal samples will be collected on Days 1 (prior to plasma administration), 3, 5, 8, 11, and 15.

Official Title
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An Open-Label, Single Arm, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill Mechanically Ventilated Participants With COVID-19 Caused by SARS-CoV-2

Conditions
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Covid-19

Intervention / Treatment
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* Biological: COVID-19 Convalescent Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ≥18 years of age Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other authorized or approved assay in any specimen collected within 72 hours prior to enrollment. Note - An exception must be requested to the Sponsor if≥72 hours since positive test. Hospitalized, on invasive mechanical ventilation or ECMO, consistent with a clinical status assessment 8-point ordinal scale severity score of 7. Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan). Patient or proxy is willing and able to provide written informed consent and comply with all protocol requirements. Exclusion Criteria: Contraindication to transfusion (e.g., severe volume overload, history of severe allergic reaction to blood products), as judged by the investigator. Clinical suspicion that the etiology of acute illness (acute decompensation) is primarily due to a condition other than COVID-19 Receipt of other investigational therapy as a part of another clinical trial. a. Note: investigational therapies used as part of clinical care, (eg, remdesivir, hydroxychloroquine) are permissible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Penn COVID-19 convalescent plasma | Biological: COVID-19 Convalescent Plasma<br>* Participants will receive 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Serious Adverse Events. | Cumulative incidence of participants with at least one serious adverse events (SAEs) at Study Day 29. | Up to Study Day 29 | 
| Time to Clinical Improvement. | Time to removal from mechanical ventilation. | Up to Study Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Status Assessment, Using 8-point Ordinal Scale, of Convalescent Plasma Administration | Time to improvement by at least 2 category from Day 1 (time to reach WHO8 <=5). WHO8 score: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities and/or requiring home oxygen; Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death | Up to Study Day 29 | 
| Clinical Status Assessment Using the National Early Warning Score (NEWS) of Convalescent Plasma Administration | Time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. NEWS assessed daily while hospitalized until discharge or death and on Days 15 and 29. Higher NEWS is worse, range from 0 to 20. | Up to Study Day 29 | 
| Incidence of New Oxygenation Use up to Day 29 of Convalescent Plasma Administration | Incidence of new oxygenation use up to Day 29. | From enrollment to Day 29. | 
| Duration of New Oxygen Use up to Day 29 of Convalescent Plasma Administration | Days of new oxygen use up to Day 29. | From enrollment to Day 29. | 
| Oxygenation | Days of supplemental oxygen while in hospital up to Study Day 29. In hospital supplemental oxygen days counted as days with a WHO8 ordinal score of 5, 6, or 7. | Daily while hospitalized up to Study Day 29. | 
| Non-invasive Ventilation/High Flow Oxygen Days up to Day 29 of Convalescent Plasma Administration. | Days of non-invasive ventilation/high flow oxygen while in hospital up to Day 29, defined as having WHO8 ordinal score of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices | Daily while in hospital to Study Day 29. | 
| Number of Subjects With at Least One Day of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration. | Number of subjects with at least one day of non-invasive ventilation (WHO8 ordinal score of 6) while in hospital | Daily while in hospital to Study Day 29. | 
| Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29 of Convalescent Plasma Administration. | Days of non-invasive ventilation/high flow oxygen up to Day 29. | Daily while in hospital to Study Day 29. | 
| Invasive Ventilation/ Extracorporeal Membrane Oxygenation(ECMO) Days | Days on Invasive Ventilator/ECMO defined as WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO | Daily while in hospital to Study Day 29 | 
| Incidence of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration. | Incidence of new mechanical ventilation or ECMO use up to Day 29. | From enrollment to Day 29. | 
| Duration of New Mechanical Ventilation or ECMO Use of Convalescent Plasma Administration. | Days of new mechanical ventilation or ECMO use up to Day 29. | From enrollment to Day 29. | 
| Duration of Hospitalization | Duration (days) of first hospitalization. Time until death or discharge or Study Day 29 | To Study Day 29 | 
| Mortality | 28 day mortality | 28 days from Study Day 1 | 
| Serious Adverse Events (SAEs) Through Day 29 of Convalescent Plasma Administration. | subjects with Serious Adverse Events (SAEs) through Day 29. | Through Study Day 29. | 
| Number of Subjects With at Least One Grade 3 and Grade 4 Clinical and/or Laboratory Adverse Events Through Day 29 of Convalescent Plasma Administration. | Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events through Day 29. | Through Study Day 29 | 
| Changes in WBC With Differential Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in Hemoglobin Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in Platelets Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in Creatinine Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in Glucose Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in Total Bilirubin Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in ALT Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29. | 
| Changes in AST Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29 | 
| Changes in PT Measurement Through Day 29 of Convalescent Plasma Administration. | Collected labs on Days 1 (baseline), 3, 5, 8, and 11 (while hospitalized), Days 15 and 29 (if attends in person visit or still hospitalized). Changes measured as difference between last measured lab value and baseline lab value. A negative value indicates last lab value > baseline lab value. | Through Day 29 |