NCT05271929

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

A Randomised Open-Label Trial of Early, Very High-Titre Convalescent Plasma Therapy in Clinically Vulnerable Individuals With Mild COVID-19

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (actual)
• Sponsor: Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

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)

Detailed description

COVIC-19 is a multicentre international, randomised, open-label adaptive superiority phase III trial to evaluate the efficacy and safety of COVID-19 convalescent plasma in the treatment of COVID-19. It is conducted in a harmonized approach in different countries in Europe. The study is randomizing adult COVID-19 patients to one of two arms (1:1 ratio): standard of care or standard of care and very high neutralizing Ab titre convalescent plasma. Randomization will be stratified by centre and by patient cohort. The control group will receive 'standard care' therapy. Neither blinding nor placebo will be used to avoid unnecessary intravenous access. Standard of care therapy may include anti-SARS-CoV-2 specific medication listed as authorized in the protocol. Centres should ensure that medications used as standard of care are used similarly for patients in both treatment arms. Participating patients will be included in 2 cohorts of vulnerable patients (cohort 1: elderly (≥ 70 years) and younger with comorbidities (cohort 1: \< 70 with comorbidities), cohort 2: immunosuppressed patients). All subjects will undergo a series of efficacy and safety assessments, including laboratory assays. Subjects will be assessed at baseline, and at Days 3, 14, 28, 90 and 180. Nasopharyngeal swabs (NP) or lower respiratory tract samples will be obtained at D1 (pre-treatment), and at D3, D14 and D28 (and monthly in case of positivity until of clearance) for cohort 2. Blood samples will be obtained at D1, D14 and D28 and on the day of hospitalization (if applicable). The trial is sponsored by the University Hospital of Besançon in France, the German Red Cross in Germany and the NHSBT in the United Kingdom.

Conditions

• COVID-19

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2022-04-01
• Primary completion: 2024-01-18
• Completion: 2024-06-17
• First posted: 2022-03-09
• Last updated: 2024-10-29

Locations

14 sites across 4 countries: France, Germany, Netherlands, United Kingdom