PMID- 33676783 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20210524 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 39 IP - 20 DP - 2021 May 12 TI - 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. PG - 2800-2809 LID - S0264-410X(21)00128-6 [pii] LID - 10.1016/j.vaccine.2021.01.074 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Joura, Elmar A AU - Joura EA AD - Medical University of Vienna, Department of Gynecology and Obstetrics, Comprehensive Cancer Center, Vienna, Austria. Electronic address: elmar.joura@meduniwien.ac.at. FAU - Ulied, Angels AU - Ulied A AD - Centre d'Atencio Primaria, EBA Centelles, Barcelona, Spain. Electronic address: angels.ulied@gmail.com. FAU - Vandermeulen, Corinne AU - Vandermeulen C AD - Leuven University Vaccinology Center, Department of Public Health and Primary Care, KU Leuven, Belgium. Electronic address: corinne.vandermeulen@kuleuven.be. FAU - Rua Figueroa, Milagrosa AU - Rua Figueroa M AD - Hospital Universitario Sanitas La Moraleja, Madrid, Spain. Electronic address: mruafigueroa@sanitas.es. FAU - Seppa, Ilkka AU - Seppa I AD - Vaccine Research Center, Tampere University, Finland. Electronic address: ilkka.seppa@tuni.fi. FAU - Hernandez Aguado, Juan Jose AU - Hernandez Aguado JJ AD - Unit of Lower Genital Tract Pathology, Department of Obstetrics and Gynecology, Hospital Universitario Infanta Leonor, Madrid, Spain. Electronic address: jjhernandeza@salud.madrid.org. FAU - Ahonen, Anitta AU - Ahonen A AD - Vaccine Research Center, Tampere University, Finland. Electronic address: anitta.ahonen@tuni.fi. FAU - Reich, Olaf AU - Reich O AD - Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria. Electronic address: olaf.reich@medunigraz.at. FAU - Virta, Miia AU - Virta M AD - Vaccine Research Center, Tampere University, Finland. Electronic address: miia.virta@tuni.fi. FAU - Perino, Antonino AU - Perino A AD - Gynecology and Obstetrics, "Villa Sofia-Cervello" Hospital, University of Palermo, Palermo, Italy. Electronic address: antonio.perino@unipa.it. FAU - Peris Tuser, Merce AU - Peris Tuser M AD - Catalan Institute of Oncology, L'Hospitalet de Llobregat, Spain. Electronic address: m.peris@iconcologia.net. FAU - Peters, Klaus AU - Peters K AD - Praxis for Gynecology, Obstetrics and Clinical Research, Berner Heerweg 157, Hamburg, Germany. Electronic address: praxis@dr-peters.net. FAU - Origoni, Massimo AU - Origoni M AD - Department of Gynecology and Obstetrics, Vita-Salute San Raffaele University School of Medicine and IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: massimo.origoni@hsr.it. FAU - Raspagliesi, Francesco AU - Raspagliesi F AD - Department of Gynecologic Oncology, Fondazione IRCCS National Cancer Institute, Milan, Italy. Electronic address: francesco.raspagliesi@istitutotumori.mi.it. FAU - Tjalma, Wiebren A A AU - Tjalma WAA AD - Multidisciplinary Breast Clinic, Gynaecological Oncology Unit, Department of Obstetrics and Gynaecology, Antwerp University Hospital (UZA), Belgium; Molecular Imaging, Pathology, Radiotherapy, and Oncology (MIPRO), Faculty of Medicine and Health Sciences, University of Antwerp, Belgium. Electronic address: wiebren.tjalma@telenet.be. FAU - Tummers, Philippe AU - Tummers P AD - Gynaecologic Oncology Unit, Department of Obstetrics and Gynaecology, Ghent University Hospital (UZ Ghent), Ghent, Belgium. Electronic address: philippe.tummers@uzgent.be. FAU - Woelber, Linn AU - Woelber L AD - Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: lwoelber@uke.uni-hamburg.de. FAU - Nieminen, Pekka AU - Nieminen P AD - Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address: pekka.nieminen@hus.fi. FAU - van Damme, Pierre AU - van Damme P AD - Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, Antwerp University, Antwerp, Belgium. Electronic address: pierre.vandamme@uantwerpen.be. FAU - Sehouli, Jalid AU - Sehouli J AD - Department of Gynecology, Competence Center for Ovarian Cancer (EKZE), Charite - University Medicine, Berlin 13353, Germany. Electronic address: jalid.sehouli@charite.de. FAU - Fiol Ruiz, Gabriel AU - Fiol Ruiz G AD - Unit of Gynecologic Oncology and Lower Genital Tract, Department of Obstetrics and Gynecology, Torrecardenas University Hospital, Almeria, Spain. Electronic address: gfiolr@gmail.com. FAU - Brucker, Sara AU - Brucker S AD - Department of Women's Health, University Hospital of Obstetrics and Gynecology, Eberhard Karls University Tuebingen, Tuebingen, Germany. Electronic address: sara.brucker@med.uni-tuebingen.de. FAU - Fehm, Tanja AU - Fehm T AD - Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, Germany. Electronic address: tanja.fehm@med.uni-duesseldorf.de. FAU - Cheon, Kyeongmi AU - Cheon K AD - Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: kyeongmi.cheon@merck.com. FAU - Rawat, Sonali AU - Rawat S AD - Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: sonali.rawat@merck.com. FAU - Luxembourg, Alain AU - Luxembourg A AD - Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: alain_luxembourg@merck.com. FAU - Wittke, Frederick AU - Wittke F AD - Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: frederick.wittke@merck.com. LA - eng SI - ClinicalTrials.gov/NCT03158220 PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210303 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Viral) RN - 0 (Papillomavirus Vaccines) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antibodies, Viral MH - Female MH - Human papillomavirus 16 MH - Human papillomavirus 18 MH - Humans MH - Immunogenicity, Vaccine MH - *Papillomavirus Infections/prevention & control MH - *Papillomavirus Vaccines/adverse effects MH - Young Adult OTO - NOTNLM OT - Adult vaccination OT - Cervical cancer OT - HPV prophylaxis OT - Human papillomavirus OT - Nine-valent human papillomavirus vaccine OT - Precancer COIS- 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 Seppa reports no conflicts of interest. Juan Jose 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.]. EDAT- 2021/03/08 06:00 MHDA- 2021/05/25 06:00 CRDT- 2021/03/07 20:28 PHST- 2020/10/01 00:00 [received] PHST- 2021/01/28 00:00 [revised] PHST- 2021/01/31 00:00 [accepted] PHST- 2021/03/08 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2021/03/07 20:28 [entrez] AID - S0264-410X(21)00128-6 [pii] AID - 10.1016/j.vaccine.2021.01.074 [doi] PST - ppublish SO - Vaccine. 2021 May 12;39(20):2800-2809. doi: 10.1016/j.vaccine.2021.01.074. Epub 2021 Mar 3.