Convalescent Plasma for Early Treatment of COVID-19

Study Overview
=================
Brief Summary
-----------------
This is a double-blinded, randomized control trial to assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma as early treatment. Participants will be randomized 2:1 to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or control (albumin 5%). This study will investigate the potential of convalescent plasma (CP) to reduce severity of and/or help treat SARS-CoV-2 disease in patients with mild disease.

Detailed Description
-----------------
There are no approved therapies for Coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposure to viruses results in an adaptive immune response that commonly include antibodies with neutralization activity. Plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Argentine hemorrhagic fever, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS). In recent work in China, an open label safety trial of CP in patients with COVID-19 suggested a substantive benefit.

Official Title
-----------------
A Phase 2 Randomized, Double-blinded Trial to Evaluate the Efficacy and Safety of Human Anti-SARS-CoV-2 Plasma for Early Treatment of COVID-19

Conditions
-----------------
SARS-CoV 2, COVID-19

Intervention / Treatment
-----------------
* Biological: Convalescent Plasma (anti-SARS-CoV-2 plasma)
* Biological: Control (albumin 5%)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be 18 years of age or older Recent close contact with a person with COVID-19, i.e. last close contact occurred within 7 days of anticipated infusion of study product. It is anticipated that most contacts will be household contacts with extensive interaction. All must meet the CDC criteria for close contacts. This includes healthcare workers at higher risk of developing severe disease. OR Recent self-reported or documented evidence of infection by nasal swab PCR that is positive for SARS-CoV-2, i.e., nasal sample was collected within 7 days or 10 days of anticipated infusion of study product for those who are asymptomatic or symptomatic, respectively. Evidence of infection by nasal swab PCR that is positive for SARS-CoV-2 at screening visit. May or may not be hospitalized. No symptoms or no more than 5 days of mild symptoms at the time of screening. Mild symptoms (rated by participant as mild and not interfering with normal daily activities) may include: Mild rhinorrhea Mild sore throat or throat irritation Mild nonproductive cough Mild fatigue (able to perform Activities of Daily Living (ADLs)) Risk for severe COVID-19 based on a risk score of ≥ 1 Calculated Risk Score of ≥ 1 point, with risk factors based on Center for Disease Control and Prevention (CDC) description Age 65-74: 1 point Age ≥ 75: 2 points Known cardiovascular disease (including hypertension): 1 point Diabetes mellitus: 1 point Pulmonary disease (COPD, moderate to severe asthma, current smoking or other): 1 point Morbid obesity: 1 point Immunocompromised state: 1 point Received a bone marrow or solid organ transplant at any time, received chemotherapy for a malignancy within the past 6 months, has an acquired or congenital immunodeficiency, currently receiving immunosuppressive or immune modulating medications, HIV with non-suppressed viral load and/or cluster of differentiation 4 (CD4+) T cell count <200 cells/mL). Exclusion Criteria: Receipt of any blood product in past 120 days. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance. Confirmed or self-reported presumed COVID-19, with symptoms that began more than 5 days prior to enrollment, and SARS-CoV-2 PCR positive sample that was collected more than 7 days prior to anticipated infusion for an asymptomatic participant or more than 10 days prior to anticipated infusion for a patient with mild symptoms at screening. Symptoms consistent with COVID---19 infection that are more than mild (as defined above) at time of screening. Symptoms consistent with COVID---19 infection that are more than mild at time of screening. History of allergic reaction to transfusion blood products Inability to complete infusion of the product within 48 hours after randomization. Resident of a long term or skilled nursing facility Known prior diagnosis of immunoglobulin A (IgA) deficiency Oxygen saturation that is < 95% at the screening visit On supplemental oxygen at time of enrollment Participation in another clinical trial of anti-viral agent(s) for COVID-19 Receipt of any COVID-19 vaccine, either as part of a clinical research trial or through routine service delivery.

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

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 150 eligible subjects will be randomized in a 2:1 ratio to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or control (albumin 5%)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma (anti-SARS-CoV-2 plasma)<br>Participants randomized to the experimental arm will receive 2 units (approximately 200 to 250 mL per unit, total 400-500mL) of convalescent plasma that was collected from a volunteer who recovered from COVID-19 disease. | Biological: Convalescent Plasma (anti-SARS-CoV-2 plasma)<br>* Convalescent Plasma that contains antibody titers against SARS-CoV-2.<br>|
| Active Comparator: Control (albumin 5%)<br>Participants randomized to the control arm will receive 2 units of 250 mL (500mL total) of albumin (human) 5% infusion. The albumin will be prepared in bags that are identical to the bags used for plasma. The similar appearance of albumin and plasma will facilitate maintaining the blinded status of subjects and most of the study staff. | Biological: Control (albumin 5%)<br>* Albumin (Human) 5% is a sterile aqueous solution for intravenous use containing the albumin component human plasma.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Severe Disease | The efficacy of treatment will be determined by rating disease severity on Day 28, or last rating evaluated, using a seven-category severity scale. | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of measurable anti-SARS-CoV-2 titers | To compare the rate of measurable anti-SARS-CoV-2 titers between recipients of CP (anti-SARS-CoV-2 plasma) versus control (albumin 5%). | Up to 90 days | 
| Rate of SARS-CoV-2 PCR Positivity | Compare the rates of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (albumin 5%). | Up to 28 days | 
| Duration of SARS-CoV-2 PCR Positivity | Compare the duration of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (albumin 5%). | Up to 28 days | 
| Levels of SARS-CoV-2 RNA | Compare the levels of SARS-CoV-2 RNA between the recipients of antiSARS-CoV-2 plasma and control (albumin 5%) | Up to 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Convalescent Plasma, Coronavirus, COVID