Safety and immunogenicity of inactivated poliovirus vaccine schedules for the post-eradication era: a randomised open-label, multicentre, phase 3, non-inferiority trial

Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule. This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at −10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference.. Safety was assessed as serious adverse events and important medical events. This study is registered on ClinicalTrials.gov, NCT03239496. From Oct 23, 2017, to Nov 13, 2018, we en