COVID-19 Convalescent Plasma for the Treatment of Hospitalized Patients With Pneumonia Caused by SARS-CoV-2.

Study Overview
=================
Brief Summary
-----------------
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 improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.

Detailed Description
-----------------
This open-label, randomized, controlled, phase 1 trial will assess the safety and efficacy of convalescent plasma in severely ill, hospitalized participants with pneumonia due to COVID-19. This study will enroll adults 18 years old and older, including pregnant women. A total of 80 eligible participants will be randomized to receive either 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19 and standard of care (treatment arm) or standard of care alone (control arm). Participants in the treatment arm will receive 2 units of convalescent plasma on Study Day 1 in addition to standard of care. Participants will be assessed on study Day 1 (pre-dose), 30 minutes after each unit of plasma, on all Study Days while hospitalized, and Study Days 15, 22, 29, and 60. All participants will undergo a series of safety and efficacy, assessments. Blood samples will be collected on Days 1 (prior to plasma administration), 3, 8, 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
-----------------
An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants With COVID-19 Pneumonia Caused by SARS-CoV-2.

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Biological: COVID-19 Convalescent Plasma


Participation Criteria
=================
Eligibility Criteria
-----------------
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 in participating facility. Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan). Abnormal respiratory status that is judged worse than baseline by the investigator and as documented at any point within 24 hours prior to randomization, consistent with ordinal scale levels 5, 6 or 7, specifically defined as: Room air saturation of oxygen (SaO2) < 93%, OR Requiring supplemental oxygen, OR Tachypnea with respiratory rate ≥30 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. Note: investigational therapies used as part of clinical care, (eg, remdesivir, hydroxychloroquine) are permissible.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1 to receive either convalescent plasma on Study Day 1 in addition to standard care or standard care alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVID-19 Convalescent plasma<br>COVID-19 Convalescent plasma on Study Day 1 in addition to standard care | Biological: COVID-19 Convalescent Plasma<br>* 2 units of COVID-19 convalescent plasma compatible with their blood type<br>|
| No Intervention: Standard care<br>Standard care alone | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Serious Adverse Events. | Number of participants with at least one serious adverse events (SAEs) up to Study Day 29. | Up to Study Day 29 | 
| Clinical Severity Score | Clinical Severity Score (CSC) measured by both survival time, time to recovery (defined by reaching levels 1-3 of the WHO modified 8-Point Ordinal Severity scale), and disease course while hospitalized and is calculated based on a procedure proposed by Shaw and Fay 2016 (https://doi.org/10.1002/sim.6950). CSC ranges from 1 to 57. Higher CSC is worse outcome. Clinical status assessment (WHO modified 8-Point Ordinal Severity scale) includes: 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Status Assessment, Time to Recovery | Time to recovery, defined by time needed to reach levels 1-3 using the WHO modified 8-Point Ordinal Severity scale assessed daily while hospitalized and on Day 15, 22, and 29: 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 | 
| National Early Warning Score (NEWS) Clinical Status Assessment | Time to discharge or to a National Early Warning Score (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 | 
| Oxygenation | Days of supplemental oxygen while in hospital. defined as days with WHO8 ordinal score of 5, 6, or 7 | Daily while hospitalized and up to Study Day 29 | 
| Incidence of New Oxygenation Use up to Day 29 | Incidence of new oxygenation use up to Day 29. | From enrollment to Day 29. | 
| Duration of New Oxygen Use up to Day 29 | Duration (days) of new oxygen use up to Day 29. | From enrollment to Day 29. | 
| Non-invasive Ventilation/High Flow Oxygen Days up to Day 29 | Days of non-invasive ventilation/high flow oxygen up to Day 29 Defined by having a WHO8 ordinal scale of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices | Daily while in hospital to Study Day 29. | 
| Number of Participants With at Least One Day on Non-invasive Ventilation/High Flow Oxygen up to Day 29 | number of participants with at least one day on non-invasive ventilation/high flow oxygen Defined by having a WHO8 ordinal scale of 6 = Hospitalized, on non-invasive ventilation or high flow oxygen devices | Daily while in hospital until Study Day 29 | 
| Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29 | Days of non-invasive ventilation/high flow oxygen up to Day 29 | Daily while in hospital to Study Day 29. | 
| Ventilator/ECMO Days to Day 29 | Days of mechanical ventilation or ECMO use (having a WHO8 ordinal score of 7 = Hospitalized, on invasive mechanical ventilation or ECMO) during the study in hospital until study day 29. | Daily while in hospital to Study Day 29 | 
| New Mechanical Ventilation or ECMO Use | number of subjects with new mechanical ventilation or ECMO use up to Day 29 since all subjects were not on mechanical ventilation or ECMO at baseline. | From enrollment to Day 29. | 
| Duration of New Mechanical Ventilation or ECMO | Days of new mechanical ventilation or ECMO use up to Day 29. | Daily while in hospital to Study 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 | 
| Number of Subjects With SAEs Through Day 29 | Number of subjects with 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 | Number of subjects with at least one Grade 3 or Grade 4 clinical and/or laboratory adverse events (AEs) through Day 29. | Through Study Day 29 | 
| Changes in WBC With Differential Through Day 29 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 Laboratory Through Day 29 | 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Convalescent plasma