Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19

Summary

* Research Question: Does convalescent plasma (CCP) collected from donors who have recovered from COVID-19 and who have a very high titre of anti-SARS-CoV-2 antibodies reduce the risk of hospitalisation (for COVID-19) or death in patients with early symptoms of acute COVID-19 who are vulnerable to this disease compared to standard of care?
* Study product: Very high antibody titre COVID-19 convalescent plasma collected more than 15 days after end of symptoms in COVID-19 patients who also had received at least one dose of a SARS-CoV-2 vaccine.
* Methodology: Multicentre, randomised, open-label, adaptive superiority trial: COVID-19 very high neutralizing Ab titre convalescent plasma vs standard care in 2 cohorts of vulnerable patients (cohort 1: elderly (≥ 70 years) and younger with comorbidities, cohort 2: immunosuppressed patients).
* Study phase: Phase 3
* Intervention: Two units of high antibody titre COVID-19 convalescent plasma to individuals randomised to the intervention group, 2 units from 2 different donors, preferably transfused on the same day. Plasma provided by convalescent vaccinated donors with a minimum antibody titre of 1:640 against delta variant (B1.617.2) or antibody concentration \>=4.000 BAU/ml in the QuantiVac anti-SARS-CoV-2 IgG ELISA or \>=20.000 U/ml in the Elecsys anti-SARS-CoV-2 CLIA
* Randomisation: 1:1 (standard of care + convalescent plasma vs. standard of care) stratified by centre (cohorts 1 and 2)

Conditions

• COVID-19

Interventions

BIOLOGICAL

Current standard of care and COVID-19 convalescent and vaccinated plasma

ABO compatible convalescent plasma infused intravenously on study day 1 (as soon as possible after randomisation) and the second on day 1 or day 2. Plasma obtained by apheresis from donors who have recovered from COVID-19 infection (at least 14 days after recovery) and have been vaccinated (at least 3 weeks after first dose of vaccine). A combination of both a SARS-CoV-infection and a SARS-CoV-2 vaccination of the donor is required - irrespective of the sequence of infection and vaccination. As far as the availability of CCP units allows, the two plasma units should have been donated by two different convalescents.

OTHER

Current standard of care

Standard of care therapy may include anti-SARS-CoV-2 specific medication such as, but not limited to: * Casirivimab * Casirivimab / Imdevimab (REGN-COV2 or Ronapreve) * Imdevimab * Sotrovimab (Xevudy) * Tixagevimab / Cilgavimab (Evusheld) * Molnupiravir (MK-4482) * Nirmatrevlir / Ritonavir (Paxlovid) * Remdesivir Centres should ensure that medications used as standard of care are used similarly for patients in both treatment arms.

Sponsors & Collaborators

• NHS Blood and Transplant

  collaborator OTHER_GOV

• Erasmus Medical Center

  collaborator OTHER

• Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen

  lead OTHER

Principal Investigators

• Pierre Tiberghien, MD, PhD · Etablissement Français du Sang, La Plaine Saint-Denis, France

• Eric Toussirot, MD, PhD · Rheumatology department, CHU Besançon, France

• Hubert Schrezenmeier, MD, PhD · German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen

• Lise Estcourt, MD, PhD · NHS Blood and Transplant, Oxford, United Kingdom

• David Roberts, MD, PhD · NHS Blood and Transplant, Oxford, United Kingdom

• Bart Rijnders, MD, PhD · Erasmus Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-04-01

Primary Completion

2024-01-18

Completion

2024-06-17

Countries

• France
• Germany
• Netherlands
• United Kingdom

Study Locations