Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study.

Background: Efficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16-26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27-45 versus 16-26 years of age.
Methods: This international, open-label study (NCT03158220) was conducted in women 16-45 years of age. Participants (16-26 years, n = 570 and 27-45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study.
Results: At month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27-45 years were compared to those in women 16-26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27-45 years to 16-26 years) was 0.60-0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27-45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16-26 years, and 85.2% and 24.1% of women 27-45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study.
Conclusions: The 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27-45 years compared with women 16-26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16-26 years to women 27-45 years of age. Clinical trial registration NCT03158220.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Elmar Joura reports grants from Merck during the conduct of the study, and personal fees from Merck Sharpe & Dohme outside the submitted work. Angels Ulied reports personal fees through her institution from GSK, NUTRICIA, and MERK, outside the submitted work. Corinne Vandermeulen reports that her university received grants from GSK, Pfizer, and Merck for clinical studies for which she was principal investigator, and no personal grants. Milagrosa Rua Figueroa reports no conflicts of interest. Ilkka Seppä reports no conflicts of interest. Juan José Hernandez Aguado reports no conflicts of interest. Anitta Ahonen reports no conflicts of interest. Olaf Reich reports no conflicts of interest. Miia Virta reports no conflicts of interest. Antonino Perino reports grant and travel support from Merck Sharp & Dohme. Merce Peris Tuser reports no conflicts of interest. Klaus Peters reports no conflicts of interest. Massimo Origoni reports no conflicts of interest. Francesco Raspagliesi reports grants from GSK, Merck Sharpe & Dohme, Roche, and Tesaro, outside the submitted work. Wiebren AA Tjalma reports no conflicts of interest. Philippe Tummers reports no conflicts of interest. Linn Woelber reports grants from Merck Sharpe & Dohme during the conduct of the study, grants and personal fees from Medac Oncology, personal fees from GSK, Jenapharm, Pfizer, Roche, Tesaro, and TEVA, and grants from Roche Diagnostics, outside the submitted work. Pekka Nieminen reports no conflicts of interest. Pierre van Damme reports his university received grants from Merck Sharpe & Dohme for the conduct of this study, grants from GSK Biologicals, Pfizer, Sanofi, Merck Sharpe & Dohme, Takeda, Baxter, CanSino China, Themis, Osivax, J&J, and Abbott, and grants from The Bill & Melinda Gates Foundation, PATH, Flemish Government, and European Union, outside the submitted work. Jalid Sehouli reports no conflicts of interest. Gabriel Fiol Ruiz reports no conflicts of interest. Sara Brucker reports no conflicts of interest. Tanja Fehm reports personal fees from Daichi Sankyo, Lilly, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, and TEVA. Kyeongmi Cheon, Sonali Rawat, Alain Luxembourg, and Frederick Wittke are current or former employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA.].
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