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Publication . Article . 2021

Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial

Benjamin Gaborit; Bernard Vanhove; Marie-Anne Vibet; Aurélie Le Thuaut; Karine Lacombe; Vincent Dubee; Florence Ader; +17 Authors
Open Access
English
Published: 01 Dec 2021 Journal: Trials, volume 22, issue 1, pages 1-17 (issn: 1745-6215, Copyright policy )
Publisher: BMC
Country: France
Abstract

Abstract Background Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. Methods Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. Discussion This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. Trial registration ClinicalTrials.gov NCT04453384, registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.

Subjects by Vocabulary

Library of Congress Subject Headings: lcsh:Medicine (General) lcsh:R5-920

Microsoft Academic Graph classification: Immunotherapy medicine.medical_treatment medicine Internal medicine medicine.medical_specialty Severity of illness Neutralizing antibody biology.protein biology Therapeutic approach business.industry business Pneumonia medicine.disease Placebo Population education.field_of_study education Randomized controlled trial law.invention law

Subjects

COVID-19, Anti-SARS-CoV-2 antibodies, Moderate pneumonia, Immunotherapy, Randomized controlled trial, Phase 2, [SDV]Life Sciences [q-bio], Pharmacology (medical), Medicine (miscellaneous), Study Protocol

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Funded by
EC| BRIGHT
Project
BRIGHT
Treat severe cases of infection at COV with XAV-19
  • Funder: European Commission (EC)
  • Project Code: 962036
  • Funding stream: H2020 | SME-2b
Validated by funder
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