Design of a Phase III immunogenicity and safety study evaluating two-dose regimens of 9-valent human papillomavirus (9vHPV) vaccine with extended dosing intervals.

HPV vaccines are widely licensed as two-dose regimens, 6-12 months apart, for adolescents. Extended intervals between doses may be necessary due to resource constraints or vaccination program disruption. This international, multicenter, open-label study (NCT04708041) will evaluate the safety and immunogenicity of two-dose 9vHPV vaccine regimens with extended intervals of 1-5 years between doses in boys/girls compared with a standard three-dose regimen in women. Participants (planned N = 700) will be enrolled into six cohorts; Cohort 0: boys/girls aged 10-15 years who received one 9vHPV vaccine dose ≥1 year before enrollment without completing the series will receive one study dose of 9vHPV vaccine at day 1; Cohorts 1-4: HPV vaccination-naïve boys/girls aged 9-14 years will receive two doses (day 1 and month 12, 24, 36, or 60); Cohort 5: HPV vaccination-naïve women aged 16-26 years will receive three doses (day 1, months 2 and 6). Primary analyses will be based on serological responses 1 month after final vaccine dose. Co-primary objectives will (1) evaluate non-inferiority of geometric mean titers in each of Cohorts 1-4 versus Cohort 5, and (2) characterize antibody responses in Cohort 0, accounting for the interval between commercial and study vaccine dose. Injection-site and systemic adverse events (AEs) will be collected for 15 days and serious AEs for 12 months post-vaccination; vaccine-related serious AEs and deaths will be collected throughout the study. Results will inform completion of vaccination in individuals who did not complete the recommended series and guide implementation of vaccination programs in resource-limited settings.