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. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05132-9.
【저자키워드】 COVID-19, Randomized controlled trial, Phase 2, Immunotherapy, anti-SARS-CoV-2 antibodies, Moderate pneumonia, breath, 【초록키워드】 Treatment, convalescent plasma, neutralizing antibody, SARS-CoV-2, coronavirus, Immunity, Pneumonia, antibody, Phase 2, Antibody Response, Infection, severe acute respiratory syndrome Coronavirus, Spike protein, Anti-viral, kidney, Prophylaxis, Replication, Drug-drug interactions, Randomized, cells, humans, Patient, plasma, Placebo, respiratory, moderate, COVID-19 patients, Heterologous, Combination, administration, Therapeutic approach, dose, long term, therapeutic option, intravenous, polyclonal antibody, acute respiratory syndrome, not adapted, Trial registration, supplementary material, acute respiratory syndrome coronavirus, infected patients, acute respiratory syndrome coronavirus 2, immunotherapies, recipients, double-blinded, placebo-controlled study, clinical benefits, clinical benefit, Registered, EudraCT, treat, pathogenic, recipient, spike protein of SARS-CoV-2, primates, pharmacodynamic studies, offer, human cell, pro-inflammatory, Administered, humanized, populations, effective, polyclonal, blunting, selected, performed, lack, evaluate, indicated, raised, determine, the spike protein, infected patient, to define, inhibiting, New, patients with SARS-CoV-2, pharmacodynamic study, treatment for COVID-19, 【제목키워드】 Efficacy, Trial, Study protocol, Phase 2, Randomized, Patient, moderate, placebo-controlled, double-blinded,