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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Covid-19 Infection; Hospitalized Children
• Intervention / Treatment: Biological: Convalescent plasma (CP)

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • Stollery Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • BC Children's Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 1X7
      • Winnipeg Children'S Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6C 2V5
      • Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
    • Montréal, Quebec, Canada, H4A 3J1
      • McGill Univ Health Ctr - Montreal Children's Hospital
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Jim Pattison Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 0 to <19 years old
2. Hospitalized with symptoms compatible with COVID-19 illness
3. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen prior to randomization.
4. ABO compatible convalescent plasma available

Exclusion Criteria:

1. Onset of symptoms began >12 days before screening
2. History of adverse reactions to blood products or other contraindication to transfusion
3. Refusal of plasma for religious or other reasons
4. Acute heart failure with fluid overload
5. 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
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological measures 1	Proportion of patients with negative virology	at day 3
Virological measures 3	Proportion of patients with negative virology	at day 10
Virological measures 4	Proportion of patients with negative virology	at day 15
Modulation of biomarkers	Exploratory analysis of biomarker differences between groups	up to 365 days
Resolution of fever	Time to fever resolution (no longer requiring fever management)	hours
Presence and titres levels	Presence and titres of IgG, IgA antibodies and neutralizing antibody titres in C19-CP group on the primary outcome and other outcomes.	at day 30
Functional measure 1	efficacy of C19-CP on respiratory measures using pediatric validated dyspnea (breathlessness) scales	up to 365 days
Functional measure 2	Evaluate the efficacy of C19-CP on quality of life (QOL) measures using Validated QOL scores (Eq-5D)	up to 365 days
Functional measure 3	Evaluate the efficacy of C19-CP on rehospitalization after discharge	up to 365 days

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: C17 Council (regulatory sponsor)
• Investigators: Study Chair: Julia Upton, MD, MPH, The Hospital for Sick Children; Study Director: Kathy Brodeur-Robb, C17 Council (regulatory sponsor)

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: covid-19; convalescent plasma therapy; hospitalized children
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 1000070143

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No