A Randomized, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of VIR-2482 in Healthy Adults for Prevention of Influenza A Illness (PENINSULA)

Background: Influenza A results in significant morbidity and mortality. VIR-2482, an engineered human monoclonal antibody with extended half-life, targets a highly conserved epitope on the stem region of influenza A hemagglutinin, and may protect against seasonal and pandemic influenza. Methods: This double-blind, randomized, placebo-controlled, phase 2 study examined the safety and efficacy of VIR-2482 for seasonal influenza A illness prevention in unvaccinated healthy adults. Participants (N = 2977) were randomized 1:1:1 to receive VIR-2482 450 mg, VIR-2482 1200 mg, or placebo via intramuscular (IM) injection. Primary and secondary efficacy endpoints were the proportions of participants with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed influenza A infection and either protocol-defined influenza-like illness (ILI) and Centers for Disease Control and Prevention (CDC)-defined ILI or World Health Organization (WHO)-defined ILI, respectively. Results: VIR-2482 450 mg and 1200 mg prophylaxis did not reduce the risk of protocol-defined ILI with RT-PCR-confirmed influenza A versus placebo (relative risk reduction [RRR], 3.8% [95% CI: -67.3, 44.6] and 15.9% [95% CI: -49.3, 52.3], respectively). At the 1200 mg dose, the RRRs in influenza A illness were 57.2% [95% CI: -2.5, 82.2] using CDC-ILI and 44.1% [95% CI: -50.5, 79.3] using WHO-ILI definitions, respectively. Serum VIR-2482 levels were similar regardless of influenza status; variants with reduced VIR-2482 susceptibility were not detected. Local injection-site reactions were mild and similar across groups. Conclusion: VIR-2482 1200 mg IM was well tolerated but did not significantly prevent protocol-defined ILI. Secondary endpoint analyses suggest this dose may have reduced influenza A illness. ### Competing Interest Statement Susanna K. Tan, Deborah Cebrik, David Plotnik, Maria L. Agostini, Keith Boundy, Wendy W. Yeh, and Philip S. Pang are employees of Vir Biotechnology, Inc and report stock ownership in Vir Biotechnology, Inc. Christy M. Hebner is a former employee and shareholder of Vir Biotechnology, Inc. and is a co-author on select Vir Biotechnology, Inc. patents. Jaynier Moya and Manuchehr Darani have nothing to disclose. Charles Fogarty reports receiving grant support from Vir Biotechnology, Inc. for conduct of the clinical trial. Frederick G. Hayden has served as a nonpaid consultant to Vir Biotechnology, Inc. and other companies involved in developing influenza therapeutics or vaccines, including Appili, Arcturus, Gilead, GSK, Janssen/JNJ, MedImmune, Medivector/Fujifilm, Merck, Ridgeback, Roche/Genentech, and Visterra. Cidara, Enanta, Shionogi, and Versatope have made charitable donations for Dr. Hayden's consulting time, and both Shionogi and Roche have provided meeting travel support. ### Clinical Trial ClinicalTrials.gov identifier, [NCT05567783][1] ### Funding Statement This study was supported by Vir Biotechnology, Inc. and with federal funds from the Department of Health and Human Services (HHS); Administration for Strategic Preparedness and Response (ASPR); and Biomedical Advanced Research and Development Authority (BARDA) under contract number 75A50122C00081. The findings and conclusions herein are those of the authors and do not necessarily represent the views of the Department of Health and Human Services or its components. ### 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: Ethics committee/IRB of WCG Institutional Review Board, Puyallup, Washington, USA gave ethical 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 Relevant data can be found within the manuscript and supplemental data. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05567783&atom=%2Fmedrxiv%2Fearly%2F2024%2F04%2F04%2F2024.04.03.24305209.atom