Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study.

Quadrivalent influenza vaccines (QIVs), which include both B lineage strains, are expected to provide broader protection than trivalent influenza vaccines (TIVs). The non-inferiority, immunogenicity, and safety of a cell culture-based investigational QIVc and 2 TIVs (TIV1c, TIV2c), in adults (≥18 y), were evaluated in this Phase III, double-blind, multicenter study. A total of 2680 age-stratified subjects were randomized (2:1:1) to receive 1 dose of QIVc (n = 1335), TIV1c (n = 676), or TIV2c (n = 669). TIV1c (B/Yamagata) and TIV2c (B/Victoria) differed only in B strain lineage. The primary objective was to demonstrate non-inferiority of the hemagglutinin-inhibition antibody responses of QIVc against TIVc, 22 d post-vaccination. Secondary objectives included the evaluation of immunogenicity of QIVc and TIVc in younger (≥18 - <65 y) and older (≥65 y) adults. Hemagglutinin inhibition assays were performed at days 1 and 22. Solicited local and systemic adverse events (AEs) were monitored for 7 d post-vaccination, and unsolicited AEs and serious AEs until day 181. QIVc met the non-inferiority criteria for all 4 vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B strain included in the TIV1c and TIV2c, when geometric mean titers and seroconversion rates with TIVc were compared at day 22. Between 48%-52% of subjects experienced ≥1 solicited AE, the most common being injection-site pain and headache. Serious AEs were reported by ≤1% of subjects, none were vaccine-related. The results indicate that QIVc is immunogenic and well tolerated in both younger and older adults. The immunogenicity and safety profiles of QIVc and TIVc were comparable at all ages evaluated.

Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials.

The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients (P<.001). Cold symptom scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults.