XAV-19 a Glyco-Humanized polyclonal antibody targeting SARS-CoV-2 accelerates the recovery of mild to moderate COVID-19 patients and keeps its neutralizing activity against Omicron and its subvariants.

Background: XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2. The safety and clinical efficacy of XAV-19 was investigated in patients with a WHO score of 2 to 4 in the WHO 7-point ordinal scale. The activity of XAV-19 against Omicron and its subvariants was assessed in vitro. Methods: A phase II/III, multicentric randomized double-blind placebo-controlled, clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in inpatients with COVID-19 requiring or not oxygen therapy and outpatients not requiring oxygen (EUROXAV trial, [NCT04928430][1]). Most patients were not vaccinated. The primary endpoint was the proportion of patients with an aggravation of COVID-19 within 8 days after treatment. Binding and neutralization of Omicron or its subvariants by XAV-19 was investigated by ELISA or with a whole virus neutralization assay. Results: Patients received either 150mg of XAV-19 (N=139) or placebo (N=140). Low enrolment forced the premature trial termination. XAV-19 was well tolerated. No difference in the primary endpoint, nor in the proportion with an improvement at day 8 (secondary endpoint) was observed between the 2 groups. For patients not requiring oxygen therapy, XAV-19 reduced the time to improvement significantly (7 days vs 14 days p=0.0159). Neutralizing activity against Omicron and BA.2, BA2.12.1, BA.4/5 and BQ1.1 subvariants was shown in vitro. Conclusions: XAV-19 did not reduce the aggravation in COVID-19 patients. While it did not bring any benefit to patients requiring oxygen, it reduced the time to improvement for patients not requiring oxygen (WHO score 2 or 3). These preliminary clinical data might indicate a therapeutic potential for patients with mild to moderate COVID-19 requiring supplementation with anti-SARS-CoV-2 neutralizing antibodies. ### Competing Interest Statement PJR, GE, FS, BV and OD are employees of Xenothera ### Clinical Trial NCT04928430 ### Funding Statement This project has received funding from Bpifrance and from the European Union Horizon 2020 research and innovation programme under grant agreement No 962036. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: -Research Ethics Committee from PUERTA DE HIERRO MAJADAHONDA UNIVERSITY HOSPITAL gave approval for this work. -Romania National Bioethics Committee of Medicine and Medical Devices gave approval for this work. -Greece National Ethics Committee gave approval for this work. -Istanbul Medipol University Clinical Research Ethics Committee gave approval for this work. -Bulgaria Ethics Committee for Clinical Trials gave approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04928430&atom=%2Fmedrxiv%2Fearly%2F2023%2F10%2F19%2F2023.10.09.23296726.atom