Dataset Information

Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study.

ABSTRACT:

Background

VIS410, a broadly neutralizing monoclonal antibody that binds the hemagglutinin stem of influenza A viruses, was safe and efficacious in a human H1N1 virus challenge study. This study evaluated the safety and tolerability of VIS410 in non-hospitalized adult patients with uncomplicated influenza A.

Methods

Patients 18 to 65 years of age with symptom onset within 72 h were randomized 1:1:1 to receive a single intravenous infusion of VIS410 4000 mg, 2000 mg, or placebo. Neuraminidase inhibitor therapy was prohibited. Treatment-emergent adverse events (TEAEs) were evaluated up to 100 days post-infusion. Influenza symptoms were assessed daily for 10 days using the FLU-PRO tool. Nasopharyngeal virus shedding was assessed by quantitative reverse-transcription PCR (qRT-PCR) and viral culture through Day 7.

Findings

Of the 150 patients randomized, 148 received study drug, and 138 were confirmed influenza A positive. Median age was 42 years; median time from symptom onset to treatment was 42 h; 93% had influenza A subtype H3N2.

Safety

TEAEs, most commonly diarrhea of mild severity, were dose-related, occurring in 55%, 35%, and 24% of the 4000 mg, 2000 mg, and placebo patients, respectively. Two serious adverse events occurred, both in placebo patients.

Symptom analyses

Baseline FLU-PRO symptom scores were balanced among groups. Mean scores were lower by Days 3 and 4 in the pooled VIS410 treatment group versus placebo (p < 0.023), with a tendency toward faster resolution by Kaplan-Meier analysis.

Virology analyses

VIS410 was associated with reduced median nasopharyngeal viral load TCID₅₀ AUC_Day7 (days × log₁₀ TCID₅₀/mL) (3.66 pooled VIS410 vs 4.78 placebo, p = 0.08) and in the subset of patients with baseline hemagglutination inhibition (HAI) titer ≤40 (overall, 74% of patients) was significantly reduced vs placebo (4.218 pooled VIS410 vs 6.152 placebo, p = 0.009). Kaplan-Meier estimated time to resolution of viral shedding was reduced (1.9 vs 3.6 days, p = 0.03) in VIS410 treated patients. There was a trend toward greater proportion of culture-negative patients by Day 3 (66.7% vs 51.1%, p = 0.11); when this analysis was limited to the subset of patients with positive baseline cultures, this difference became more pronounced (63.2% vs 42.5%, p = 0.053). No differences were observed in nasopharyngeal influenza qRT-PCR profiles, which represent both live and neutralized virus.

Interpretation

VIS410 was safe and well tolerated in adults with uncomplicated influenza A, with favorable effects on symptom resolution and virus replication.

Trial registration

Clinical Trials: NCT02989194.

Funding

This project was funded in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under Contract No. HHSO100201500018C.

SUBMITTER: Hershberger E

PROVIDER: S-EPMC6412085 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study.

Hershberger Ellie E Sloan Susan S Narayan Kristin K Hay Catherine A CA Smith Patrick P Engler Frank F Jeeninga Rienk R Smits Saskia S Trevejo Jose J Shriver Zach Z Oldach David D

EBioMedicine 20190109

<h4>Background</h4>VIS410, a broadly neutralizing monoclonal antibody that binds the hemagglutinin stem of influenza A viruses, was safe and efficacious in a human H1N1 virus challenge study. This study evaluated the safety and tolerability of VIS410 in non-hospitalized adult patients with uncomplicated influenza A.<h4>Methods</h4>Patients 18 to 65 years of age with symptom onset within 72 h were randomized 1:1:1 to receive a single intravenous infusion of VIS410 4000 mg, 2000 mg, or placebo. Ne ...[more]

PMID: 30638863

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Dataset Information

Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study.

Background

Methods

Findings

Safety

Symptom analyses

Virology analyses

Interpretation

Trial registration

Funding

Publications

Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study.

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