Efficacy of Human Coronavirus-immune Convalescent Plasma for the Treatment of COVID-19 Disease in Hospitalized Children

Study Overview
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Brief Summary
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This is a multicentered, open-label, randomized controlled Phase 2 trial to evaluate the safety and efficacy of providing human coronavirus-immune convalescent plasma as treatment for COVID-19 disease in hospitalized children in the context of the COVID-19 pandemic.

Detailed Description
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SARS-CoV-2 viral infection resulting in COVID-19 disease has recently been designated by the World Health Organization as a global pandemic. Outbreak forecasting and mathematical models suggest that the number of COVID-19 cases will continue to rise over the coming weeks and months. There is an urgent public health need for rapid development of novel interventions. This protocol aims to use passive antibody therapy via convalescent plasma from SARS-CoV-2-infected patients who have developed antibody immunity, COVID-19 convalescent plasma (C19-CP), as treatment for hospitalized children with COVID-19 disease at pediatric academic hospitals across Canada. The unknown role for convalescent plasma in treating COVID-19 necessitates further study.

Official Title
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A Randomized, Multicentered, Open-label Phase 2 Clinical Trial of the Safety and Efficacy of Human Coronavirus- Immune Convalescent Plasma for the Treatment of COVID-19 Disease in Hospitalized Children

Conditions
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Hospitalized Children, Covid-19 Infection

Intervention / Treatment
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* Biological: Convalescent plasma (CP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 0 to <19 years old Hospitalized with symptoms compatible with COVID-19 illness Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen prior to randomization. ABO compatible convalescent plasma available Exclusion Criteria: Onset of symptoms began >12 days before screening History of adverse reactions to blood products or other contraindication to transfusion Refusal of plasma for religious or other reasons Acute heart failure with fluid overload Any condition or diagnosis, that could in the opinion of the Site Principal Investigator interfere with the participant's ability to comply with study instructions, or put the participant at risk Anticipated discharge within 24 hours Note: The intent of this exclusion criteria is to only include participants with acute COVID-19 infections. This protocol is not intended to include participants with post-infectious complications. In cases where the distinction is not clear, participant eligibility will be discussed with the study steering committee prior to enrollment.

Ages Eligible for Study
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Maximum 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: Subjects will be randomized to receive either standard of care (SoC) products (control) or COVID-19 convalescent plasma (C19-CP) plus standard of care while being hospitalized for COVID-19 (ratio 1:2). The intervention will consist of a single transfusion of convalescent plasma.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma + Standard of Care (C19-CP + SoC)<br>Participants will receive COVID-19 convalescent plasma (C19-CP) plus standard of care while being hospitalized for COVID-19. | Biological: Convalescent plasma (CP)<br>* Participants will receive one infusion of convalescent plasma proportional to their weight (10 mL/kg), up to a maximum of 500 mL<br>|
| No Intervention: Standard of Care (SoC)<br>Participants will receive standard of care while being hospitalized for COVID-19. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical recovery | defined in the last 24 hours as normal respiratory and heart rate (or return to baseline, absence of fever, absence of low blood pressure, oxygen saturation greater than 94% or room air (or return to baseline), no need for intravenous fluids (or return to baseline) | at day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined mortality/intubation | Proportion of patients experiencing death in hospital (Yes/No) 30 days | at 30 day | 
| Respiratory status-1 | Proportion of patients experiencing Intubation (Yes/No) | at 30 days | 
| Respiratory status-2 | time to intubation | time from admission to intubation | 
| Respiratory status-3 | Mean number of ventilator-free days in 30 days | from admission to day 30 of hospitalization | 
| respiratory status -4 | Mean number of ventilator days in 30 days | from admission to day 30 of hospitalization | 
| respiratory status -5 | The number of oxygen free days in the first 30 days or the incidence and duration of new oxygen use during the trial, defined as oxygen use that was not present at time of randomization but occurs subsequently | from admission to day 30 of hospitalization | 
| respiratory status-6 | The proportion of patients needing ECMO in 30 days | at 30 days | 
| Mortality 1a | Time to in-hospital death censored | at 30 days | 
| Mortality 1b | Time to in-hospital death censored | at 90 days | 
| Mortality 2a | Proportion of patients with Survival status | at 30 days | 
| Mortality 2b | Proportion of patients with Survival status | at 90 days | 
| Care and Critical Care | Length of hospitalization and stay in the ICU | at 30 days | 
| organ systems: renal | The proportion of patients needing renal replacement therapy | up to 365 days | 
| organ systems: cardiac | The proportion of patients developing myocarditis | up to 365 days | 
| Transfusion-associated adverse events (AE) | The proportion of patients developing adverse events to the treatment arm, C19-CP as assessed by Proposed Standard definitions for surveillance of non-infectious adverse transfusion reactions. | up to 365 days | 
| Safety of the intervention | cumulative incidence of severe and life-threatening AEs and severe AEs | up to 365 days | 
| organ systems: multi-system inflammatory disease | The proportion of patients developing multi-system inflammatory disease | up to 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid-19, hospitalized children, convalescent plasma therapy