Safety and Efficacy of MHAA4549A, a Broadly Neutralizing Monoclonal Antibody, in a Human Influenza A Challenge Model: A Phase 2 Randomized Trial [PublishAheadOfPrint]

BACKGROUND: MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. Safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV-challenge model.

METHODS: One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24–36 hours later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1200, or 3600 mg) or a standard oral dose of oseltamivir. Subjects were assessed for safety, pharmacokinetics (PK), and immunogenicity. The intent-to-treat-infected (ITTI) population was assessed for changes in viral load, influenza symptoms, and inflammatory biomarkers.

RESULTS: MHAA4549A was well tolerated in all IAV-challenge subjects. 3600-mg MHAA4549A significantly reduced viral burden relative to placebo as determined by the area under the curve (AUC) of nasopharyngeal virus infection, quantified using quantitative PCR (98%) and 50% tissue culture infective dose (TCID₅₀) assays (100%). Peak viral load, duration of viral shedding, influenza symptoms scores, mucus weight, and inflammatory biomarkers were also reduced. Serum PK was linear with a half-life of ~23 days. No MHAA4549A-treated subjects developed anti-drug antibodies.

CONCLUSIONS: MHAA4549A was well tolerated, and demonstrated statistically significant and substantial antiviral activity in an IAV-challenge model.

REGISTRY: ClinicalTrials.gov, NCT01980966.

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