A Phase III trial for safety and Vaccine effectiveness of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy adults aged 18-64 years in Nakhon Phanom

Abstract

Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. A Phase III, double blind, randomized controlled trial was conducted from Sep 2019 - Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. The amount of 4,284 participants were randomized in a ratio of 3:3:1 to compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo and non-inferiority compared to active comparator comparing RT-PCR-confirmed influenza virus infection within 12 months. At 7 days safety was also assessed. The trial enrolled 4,284 participants (Tri Fluvac=1,836; placebo=1,836; active comparator=612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000 PY; 0 comparator). The absolute protective efficacy was 46.4 (95% CI= -22.0-76.5) compared with placebo. The adverse and severe adverse events occurred in 175 (9.5%), 177 (10.8%) and 66 (10.8%) in Tri Fluvac, placebo and comparator respectively, however it was no significant between Tri Fluvac and comparator group with p-value=0.437. Tri Fluvac was well tolerated, Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.