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

• ClinicalTrials.gov Identifier: NCT04377568
• Recruitment Status: Withdrawn
• First Posted: May 6, 2020
• Last Update Posted: April 23, 2021
• Sponsor: The Hospital for Sick Children
• Collaborator: C17 Council (regulatory sponsor)
• Information provided by (Responsible Party): Julia Upton, The Hospital for Sick Children

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hospitalized Children; Covid-19 Infection	Biological: Convalescent plasma (CP)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 7, 2020
• Estimated Primary Completion Date: December 1, 2021
• Estimated Study Completion Date: May 1, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Clinical recovery [ Time Frame: at day 30 ]
   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)

Secondary Outcome Measures :

1. Combined mortality/intubation [ Time Frame: at 30 day ]
   Proportion of patients experiencing death in hospital (Yes/No) 30 days
2. Respiratory status-1 [ Time Frame: at 30 days ]
   Proportion of patients experiencing Intubation (Yes/No)
3. Respiratory status-2 [ Time Frame: time from admission to intubation ]
   time to intubation
4. Respiratory status-3 [ Time Frame: from admission to day 30 of hospitalization ]
   Mean number of ventilator-free days in 30 days
5. respiratory status -4 [ Time Frame: from admission to day 30 of hospitalization ]
   Mean number of ventilator days in 30 days
6. respiratory status -5 [ Time Frame: from admission to day 30 of hospitalization ]
   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
7. respiratory status-6 [ Time Frame: at 30 days ]
   The proportion of patients needing ECMO in 30 days
8. Mortality 1a [ Time Frame: at 30 days ]
   Time to in-hospital death censored
9. Mortality 1b [ Time Frame: at 90 days ]
   Time to in-hospital death censored
10. Mortality 2a [ Time Frame: at 30 days ]
    Proportion of patients with Survival status
11. Mortality 2b [ Time Frame: at 90 days ]
    Proportion of patients with Survival status
12. Care and Critical Care [ Time Frame: at 30 days ]
    Length of hospitalization and stay in the ICU
13. organ systems: renal [ Time Frame: up to 365 days ]
    The proportion of patients needing renal replacement therapy
14. organ systems: cardiac [ Time Frame: up to 365 days ]
    The proportion of patients developing myocarditis
15. Transfusion-associated adverse events (AE) [ Time Frame: up to 365 days ]
    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.
16. Safety of the intervention [ Time Frame: up to 365 days ]
    cumulative incidence of severe and life-threatening AEs and severe AEs
17. organ systems: multi-system inflammatory disease [ Time Frame: up to 365 days ]
    The proportion of patients developing multi-system inflammatory disease

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: up to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Canada, Alberta

Alberta Children's Hospital

Calgary, Alberta, Canada, T3B 6A8

Stollery Children's Hospital

Edmonton, Alberta, Canada, T6G 2B7

Canada, British Columbia

BC Children's Hospital

Vancouver, British Columbia, Canada, V6H 3V4

Canada, Manitoba

Winnipeg Children's Hospital

Winnipeg, Manitoba, Canada, R3C 1X7

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Ontario

McMaster Children's Hospital

Hamilton, Ontario, Canada, L8N 3Z5

Kingston Health Sciences Centre

Kingston, Ontario, Canada, K7L 2V7

Children's Hospital

London, Ontario, Canada, N6C 2V5

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

The Hospital for Sick Children

Toronto, Ontario, Canada, M5G1X8

Canada, Quebec

CHU Sainte-Justine

Montréal, Quebec, Canada, H3T 1C5

McGill Univ Health Ctr - Montreal Children's Hospital

Montréal, Quebec, Canada, H4A 3J1

Canada, Saskatchewan

Jim Pattison Children's Hospital

Saskatoon, Saskatchewan, Canada, S7N 0W8

Sponsors and Collaborators

The Hospital for Sick Children

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)

More Information

• Responsible Party: Julia Upton, Staff Physician, Allergy and Immunology, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT04377568
• Other Study ID Numbers: 1000070143
• First Posted: May 6, 2020
• Last Update Posted: April 23, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Julia Upton, The Hospital for Sick Children:

covid-19; hospitalized children; convalescent plasma therapy

Additional relevant MeSH terms:

Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases