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BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multi-center study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n=400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (TEAE) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n=73) or comparator (n=24). There were 24 participants (34%, 95% CI, 23-47%) with a TEAE in the solithromycin group and 7 (29%, 95% CI, 13-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47-72%) and 68% (95% CI, 43-87%) for the solithromycin and comparator groups, respectively. CONCLUSION: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

Additional File 5: Figure S1. Observed and Estimated Year 10 rSBA GMTs* by Primary Vaccine for Each Meningococcal Serogroup. This figure compares observed rSBA GMTs in the persistence phase with modeling estimated data for each meningococcal serogroup.

Additional File 3: Table S2. Subjects* With rSBA Titers ≥1:8 and ≥1:128 and GMTs 7–10 Years After Primary Vaccination. This table displays antibody persistence data for primary vaccination with MenACWY-TT or MenACWY-PS at Years 7, 8, 9, and 10 after vaccination, including rSBA titers and rSBA GMTs.

Additional File 4: Table S3. Subjects* With rSBA Titers ≥1:8 7–10 Years After Primary Vaccination by Age Group. This table displays rSBA titers for primary vaccination with MenACWY-TT or MenACWY-PS at Years 7, 8, 9, and 10 after vaccination by age group.

Additional File 2: Supplementary Appendix. Immunogenicity Modeling Methods. This document provides a summary of the approach used to model immunogenicity, including model fit and coding information.

Additional File 7: Table S5. Subjects* Reporting Reactogenicity Events After MenACWY-TT Booster Dose by Intensity and Primary Vaccine Group. This table displays reactogenicity data after a booster dose with MenACWY-TT by primary vaccine and intensity of event.

Additional File 6: Table S4. Subjects* With rSBA Titers ≥1:8 and ≥1:128 Before and 1 Month After MenACWY-TT Booster Dose. This table displays immunogenicity data before and after a booster dose with MenACWY-TT for each meningococcal serogroup.

Additional File 1: Table S1. Intensity Scales for Local and General Reactogenicity Events. This table provides an overview of the intensity scales used to describe local and general reactogenicity events.

Background: A quadrivalent split-virion inactivated influenza vaccine (VaxigripTetre (TM), Sanofi Pasteur; IIV4) containing two A strains (H1N1 and H3N2) and B strains from both lineages (Victoria and Yamagata) was approved in Europe in 2016 for individuals aged >= 3 years. This study examined the efficacy and safety of IIV4 in children aged 6-35 months. Methods: This was a phase III randomised controlled trial conducted in Latin America, Asia, Africa, and Europe during the Northern Hemisphere 2014/2015 and 2015/2016 and Southern Hemisphere 2014 and 2015 influenza seasons. Healthy children aged 6-35 months not previously vaccinated against influenza were randomised to receive two full doses 28 days apart of IIV4, placebo, the licensed trivalent splitvirion inactivated vaccine (IIV3), an investigational IIV3 containing a B strain from the alternate lineage. The primary objective was to demonstrate efficacy against influenza illness caused by any strain or vaccine-similar strains. Results: The study enrolled 5806 participants. Efficacy, assessed in 4980 participants completing the study according to protocol, was demonstrated for IIV4. Vaccine efficacy was 50.98% (97% CI, 37.36-61.86%) against influenza caused by any A or B type and 68.40% (97% CI, 47.07-81.92%) against influenza caused by vaccine-like strains. Safety profiles were similar for IIV4, placebo, and the IIV3s, although injection-site reactions were slightly more frequent for IIV4 than placebo. Conclusions: IIV4 was safe and effective for protecting children aged 6-35 months against influenza illness caused by vaccine-similar or any circulating strains. (C) 2018 The Authors. Published by Elsevier Ltd.