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

Elmar A. Joura; Angels Ulied; Corinne Vandermeulen; Milagrosa Rua Figueroa; Ilkka Seppä; Juan José Hernandez Aguado; Anitta Ahonen; Olaf Reich; Miia Virta; Antonino Perino; Merce Peris Tuser; Klaus Peters; Massimo Origoni; Francesco Raspagliesi; Wiebren A.A. Tjalma; Philippe Tummers; Linn Woelber; Pekka Nieminen; Pierre van Damme; Jalid Sehouli; Gabriel Fiol Ruiz; Sara Brucker; Tanja Fehm; Kyeongmi Cheon; Sonali Rawat; Alain Luxembourg; Frederick Wittke

doi:10.1016/j.vaccine.2021.01.074

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

Elmar A. Joura
, Angels Ulied
, Corinne Vandermeulen
, Milagrosa Rua Figueroa
, Ilkka Seppä
, Juan José Hernandez Aguado
, Anitta Ahonen
, Olaf Reich
, Miia Virta
, Antonino Perino
, Merce Peris Tuser
, Klaus Peters
, Massimo Origoni
, Francesco Raspagliesi
, Wiebren A.A. Tjalma
, Philippe Tummers
, Linn Woelber
, Pekka Nieminen
, Pierre van Damme
, Jalid Sehouli

Gabriel Fiol Ruiz, Sara Brucker, Tanja Fehm, Kyeongmi Cheon, Sonali Rawat, Alain Luxembourg, Frederick Wittke^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

40 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2800-2809
Number of pages	10
Journal	Vaccine
Volume	39
Issue number	20
DOIs	https://doi.org/10.1016/j.vaccine.2021.01.074
Publication status	Published - 12 May 2021
Publication type	A1 Journal article-refereed

Funding

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.]. Medical writing support, under the direction of the authors, was provided by Chris Whittle, PhD, of CMC AFFINITY, McCann Health Medical Communications funded by Merck & Co., Inc., Kenilworth, NJ, USA, in accordance with Good Publication Practice (GPP3) guidelines.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Adult vaccination
Cervical cancer
HPV prophylaxis
Human papillomavirus
Nine-valent human papillomavirus vaccine
Precancer

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

Access to Document

10.1016/j.vaccine.2021.01.074

Cite this

Joura, E. A., Ulied, A., Vandermeulen, C., Rua Figueroa, M., Seppä, I., Hernandez Aguado, J. J., Ahonen, A., Reich, O., Virta, M., Perino, A., Peris Tuser, M., Peters, K., Origoni, M., Raspagliesi, F., Tjalma, W. A. A., Tummers, P., Woelber, L., Nieminen, P., van Damme, P., ... Wittke, F. (2021). 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. Vaccine, 39(20), 2800-2809. https://doi.org/10.1016/j.vaccine.2021.01.074

@article{9da4a7bacf39497e893f46892ec86bbc,

title = "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",

abstract = "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.",

keywords = "Adult vaccination, Cervical cancer, HPV prophylaxis, Human papillomavirus, Nine-valent human papillomavirus vaccine, Precancer",

author = "Joura, \{Elmar A.\} and Angels Ulied and Corinne Vandermeulen and \{Rua Figueroa\}, Milagrosa and Ilkka Sepp{\"a} and \{Hernandez Aguado\}, \{Juan Jos{\'e}\} and Anitta Ahonen and Olaf Reich and Miia Virta and Antonino Perino and \{Peris Tuser\}, Merce and Klaus Peters and Massimo Origoni and Francesco Raspagliesi and Tjalma, \{Wiebren A.A.\} and Philippe Tummers and Linn Woelber and Pekka Nieminen and \{van Damme\}, Pierre and Jalid Sehouli and \{Fiol Ruiz\}, Gabriel and Sara Brucker and Tanja Fehm and Kyeongmi Cheon and Sonali Rawat and Alain Luxembourg and Frederick Wittke",

note = "Funding Information: 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 Sepp{\"a} reports no conflicts of interest. Juan Jos{\'e} 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.]. Funding Information: Medical writing support, under the direction of the authors, was provided by Chris Whittle, PhD, of CMC AFFINITY, McCann Health Medical Communications funded by Merck \& Co., Inc., Kenilworth, NJ, USA, in accordance with Good Publication Practice (GPP3) guidelines. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = may,

day = "12",

doi = "10.1016/j.vaccine.2021.01.074",

language = "English",

volume = "39",

pages = "2800--2809",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

number = "20",

}

Joura, EA, Ulied, A, Vandermeulen, C, Rua Figueroa, M, Seppä, I, Hernandez Aguado, JJ, Ahonen, A, Reich, O, Virta, M, Perino, A, Peris Tuser, M, Peters, K, Origoni, M, Raspagliesi, F, Tjalma, WAA, Tummers, P, Woelber, L, Nieminen, P, van Damme, P, Sehouli, J, Fiol Ruiz, G, Brucker, S, Fehm, T, Cheon, K, Rawat, S, Luxembourg, A & Wittke, F 2021, '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', Vaccine, vol. 39, no. 20, pp. 2800-2809. https://doi.org/10.1016/j.vaccine.2021.01.074

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. / Joura, Elmar A.; Ulied, Angels; Vandermeulen, Corinne et al.
In: Vaccine, Vol. 39, No. 20, 12.05.2021, p. 2800-2809.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - 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

T2 - An open-label phase 3 study

AU - Joura, Elmar A.

AU - Ulied, Angels

AU - Vandermeulen, Corinne

AU - Rua Figueroa, Milagrosa

AU - Seppä, Ilkka

AU - Hernandez Aguado, Juan José

AU - Ahonen, Anitta

AU - Reich, Olaf

AU - Virta, Miia

AU - Perino, Antonino

AU - Peris Tuser, Merce

AU - Peters, Klaus

AU - Origoni, Massimo

AU - Raspagliesi, Francesco

AU - Tjalma, Wiebren A.A.

AU - Tummers, Philippe

AU - Woelber, Linn

AU - Nieminen, Pekka

AU - van Damme, Pierre

AU - Sehouli, Jalid

AU - Fiol Ruiz, Gabriel

AU - Brucker, Sara

AU - Fehm, Tanja

AU - Cheon, Kyeongmi

AU - Rawat, Sonali

AU - Luxembourg, Alain

AU - Wittke, Frederick

N1 - Funding Information: 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.]. Funding Information: Medical writing support, under the direction of the authors, was provided by Chris Whittle, PhD, of CMC AFFINITY, McCann Health Medical Communications funded by Merck & Co., Inc., Kenilworth, NJ, USA, in accordance with Good Publication Practice (GPP3) guidelines. Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021/5/12

Y1 - 2021/5/12

N2 - 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.

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.

KW - Adult vaccination

KW - Cervical cancer

KW - HPV prophylaxis

KW - Human papillomavirus

KW - Nine-valent human papillomavirus vaccine

KW - Precancer

U2 - 10.1016/j.vaccine.2021.01.074

DO - 10.1016/j.vaccine.2021.01.074

M3 - Article

C2 - 33676783

AN - SCOPUS:85101868414

SN - 0264-410X

VL - 39

SP - 2800

EP - 2809

JO - Vaccine

JF - Vaccine

IS - 20

ER -

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

Abstract

Funding

UN SDGs

Keywords

Publication forum classification

ASJC Scopus subject areas

Access to Document

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Cite this

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