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 injection. Primary and secondary efficacy endpoints were the proportions of participants with reverse transcriptase-polymerase chain reaction-confirmed influenza A infection and either protocol-defined influenza-like illness (ILI) and Centers for Disease Control and Prevention-defined ILI or World Health Organization-defined ILI, respectively.

Results: VIR-2482 450 mg and 1200 mg prophylaxis did not reduce the risk of protocol-defined ILI with reverse transcriptase-polymerase chain reaction-confirmed influenza A versus placebo (relative risk reduction, 3.8% [95% confidence interval (CI), -67.3 to 44.6] and 15.9% [95% CI, -49.3 to 52.3], respectively). At the 1200-mg dose, the relative risk reductions in influenza A illness were 57.2% (95% CI: -2.5 to 82.2) using Centers for Disease Control and Prevention ILI and 44.1% (95% CI: -50.5 to 79.3) using World Health Organization 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.

Conclusions: VIR-2482 1200 mg intramuscular was well tolerated but did not significantly prevent protocol-defined ILI. Secondary endpoint analyses suggest this dose may have reduced influenza A illness. Trial registration: ClinicalTrials.gov identifier, NCT05567783.