Convalescent Plasma to Limit SARS-CoV-2 Associated Complications

Study Overview
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Brief Summary
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To assess the efficacy and safety of Human coronavirus immune plasma (HCIP) to reduce the risk of hospitalization or death, the duration of symptoms and duration of nasopharyngeal or oropharyngeal viral shedding.

Detailed Description
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The purpose of this randomized, double-blind, controlled, phase 2 trial is to evaluate the efficacy of treatment with HCIP in reducing hospitalization and death prior to hospitalization among outpatient adults who have RNA detection test-confirmed COVID-19 AND have developed any symptoms of COVID-19 including but not limited to fever, cough, or other COVID associated symptoms like anosmia. Ambulatory/outpatient adults subjects 18 years of age or older, regardless of risk factors for severe illness may participate. A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.

Official Title
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Comparison of the Efficacy and Safety of Human Coronavirus Immune Plasma (HCIP) vs. Control (SARS-CoV-2 Non-immune) Plasma Among Outpatients With Symptomatic COVID-19

Conditions
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SARS-CoV 2

Intervention / Treatment
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* Biological: SARS-CoV-2 convalescent plasma
* Biological: Plasma from a volunteer donor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Competent and capable to provide informed consent • Positive molecular test for presence of SARS-CoV-2 in fluid collected by saliva for antigen, oropharyngeal or nasopharyngeal swab Experiencing any symptoms of COVID-19 including but not limited to fever(T> 100.5º F), cough, or other COVID associated symptoms like anosmia ≤ 8 days since the first symptoms of COVID-19 ≤ 8 days since first positive SARS-CoV-2 RNA test Able and willing to comply with protocol requirements listed in the informed consent Exclusion Criteria: Hospitalized or expected to be hospitalized within 24 hours of enrollment Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance History of prior reactions to transfusion blood products Inability to complete therapy with the study product within 24 hours after enrollment Receiving any treatment drug for COVID-19 within 14 days prior to screening evaluation (monoclonal antibodies, compassionate use or study trial related). Steroid treatment at any time does not affect study eligibility

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SARS-CoV-2 convalescent plasma<br>SARS-CoV-2 convalescent plasma (1 cup; minimum of 175 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 and after July 2021 meets FDA criteria for high titer plasma. | Biological: SARS-CoV-2 convalescent plasma<br>* SARS-CoV-2 convalescent plasma (1 cup; minimum of 175 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 and after July 2021 meets FDA criteria for high titer plasma.<br>* Other names: Human coronavirus immune plasma (HCIP);|
| Active Comparator: Standard Control plasma<br>Plasma collected from a volunteer donor prior to January 1, 2020 will not be tested for SARS-CoV-2 antibodies. Plasma collected after December 31, 2019 will be confirmed as SARS-CoV-2 seronegative. | Biological: Plasma from a volunteer donor<br>* Plasma collected from a volunteer donor prior to January 1, 2020 will not be tested for SARS-CoV-2 antibodies. Plasma collected after December 31, 2019 will be confirmed as SARS-CoV-2 seronegative.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization | Cumulative Number measured as the proportion of subjects who were hospitalized or who died prior to hospitalization | Up to day 28 | 
| Cumulative Incidence of Severe Infusion Reactions | Cumulative incidence measured as rate per person-years experiencing treatment-related severe infusion reactions during the study period. | Up to day 28 | 
| Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events | Cumulative incidence measured as rate per person-years experiencing a Grade 3 or higher. | Up to day 90 | 
| Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS) | Cumulative incidence measured as rate per person-years of treatment-related severe Acute Respiratory Distress Syndrome (ARDS) during the study period. | Up to day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum SARS-CoV-2 Antibody Titers by Visit | Geometric mean Spike Receptor Binding Domain (RBD) titers at day 0, 14, 28 and 90 between the randomized arms. | Days 0, 14, 28 and 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19