TY - JOUR
T1 - Safety profile of the adjuvanted recombinant zoster vaccine
T2 - Pooled analysis of two large randomised phase 3 trials
AU - for the ZOE-50/70 Study Group
AU - López-Fauqued, Marta
AU - Campora, Laura
AU - Delannois, Frédérique
AU - El Idrissi, Mohamed
AU - Oostvogels, Lidia
AU - De Looze, Ferdinandus J.
AU - Diez-Domingo, Javier
AU - Heineman, Thomas C.
AU - Lal, Himal
AU - McElhaney, Janet E.
AU - McNeil, Shelly A.
AU - Yeo, Wilfred
AU - Tavares-Da-Silva, Fernanda
AU - Ahonen, Anitta
AU - Avelino-Silva, Thiago Junquera
AU - Barba-Gomez, Jose Fernando
AU - Berglund, Johan
AU - Cuixart, Carlos Brotons
AU - Caso, Covadonga
AU - Chlibek, Roman
AU - Choi, Won Suk
AU - Cunningham, Anthony L.
AU - Desole, Maria Guiseppina
AU - Eizenberg, Peter
AU - Esen, Meral
AU - Espié, Emmanuelle
AU - Gervais, Pierre
AU - Ghesquiere, Wayne
AU - Godeaux, Olivier
AU - Gorfinkel, Iris
AU - Hui, David Shu Cheong
AU - Hwang, Shinn Jang
AU - Korhonen, Tiina
AU - Kovac, Martina
AU - Ledent, Edouard
AU - Leung, Edward
AU - Levin, Myron J.
AU - Perez, Silvia Narejos
AU - Neto, Jose Luiz
AU - Pauksens, Karlis
AU - Poder, Airi
AU - de la Pinta, Maria Luisa Rodriguez
AU - Rombo, Lars
AU - Schwarz, Tino F.
AU - Smetana, Jan
AU - Staniscia, Tommaso
AU - Tinoco, Juan Carlos
AU - Toma, Azhar
AU - Vastiau, Ilse
AU - Vesikari, Timo
N1 - Funding Information:
ZOE-50/70 Study group: Anitta Ahonen (University of Tampere, Järvenpää Vaccine Clinic, Finland), Thiago Junquera Avelino-Silva (University of São Paulo Medical School, Brazil), Jose Fernando Barba-Gomez (Instituto Dermatológico de Jalisco, Mexico), Johan Berglund (Blekinge Institute of Technology, Sweden), Carlos Brotons Cuixart (EAP Sardenya, Spain), Covadonga Caso (Hospital Clínico San Carlos, Spain), Roman Chlibek (University of Defence, Faculty of Military Health Sciences, Czech Republic), Won Suk Choi (Korea University College of Medicine, Republic of Korea), Anthony L. Cunningham (Westmead Institute for Medical Research, University of Sydney, Australia), Maria Guiseppina Desole (Servizio di Igiene Pubblica, Italy), Peter Eizenberg (Doctors of Ivanhoe, Australia), Meral Esen (Institut für Tropenmedizin, University Clinic of Tübingen, Germany), Emmanuelle Espié (GSK, Belgium), Pierre Gervais (Q&T Research Sherbrooke, Canada), Wayne Ghesquiere (University of British Columbia, Canada), Olivier Godeaux (GSK, Belgium, during the conduct of the ZOE-50/70 trials), Iris Gorfinkel (York University, Canada), David Shu Cheong Hui (Prince of Wales Hospital, Hong Kong), Shinn-Jang Hwang (Taipei Veterans General Hospital and National Yang Ming University School of Medicine, Taiwan), Tiina Korhonen (Vaccine Research Centre, University of Tampere Medical School, Tampere, Finland) Martina Kovac (GSK, USA), Edouard Ledent (GSK, Belgium), Edward Leung (Hong Kong Association of Gerontology, Hong Kong), Myron J. Levin (University of Colorado Anschutz Medical Campus, USA), Silvia Narejos Perez (CAP Centelles, Spain), Jose Luiz Neto (Instituto A. Z. de Pesquisa e Ensino, Brazil), Karlis Pauksens (Uppsala University Hospital, Sweden), Airi Poder (Kliiniliste Uuringute Keskus, Estonia), Maria Luisa Rodriguez de la Pinta (Hospital Puerta de Hierro, Spain), Lars Rombo (Uppsala University, Sweden), Tino F. Schwarz (Standort Juliusspital, Germany), Jan Smetana (University of Defence, Faculty of Military Health Sciences, Czech Republic), Tommaso Staniscia (University G. d'Annunzio of Chieti-Pescara, Italy), Juan Carlos Tinoco (Hospital General de Durango, Mexico), Azhar Toma (Manna Research, Canada), Ilse Vastiau (GSK, Belgium), Timo Vesikari (University of Tampere, Finland), Antonio Volpi (A.O. Univesitaria Policlinico Tor Vergata, Italy), Daisuke Watanabe (Kobe University Graduate School of Medicine, Japan), Lily Yin Weckx (Federal University of Sao Paulo, Brazil), Toufik Zahaf (GSK, Belgium). The authors would like to thank all study participants, their families, the clinical investigators and sites’ staff involved in the ZOE-50/70 trials, as well as the GSK global and local clinical study teams; Catherine Dettori and Issam Jamiai (4Clinics); Lina Perez-Breva, and Esther Soriano (FISABIO-Public Health, Spain); Arnaud Didierlaurent, Nicolas Smoes and Anne-Sophie Vilain (GSK). The authors also acknowledge XPE Pharma & Science platform c/o GSK for editorial assistance and manuscript coordination. Jarno Jansen and Alpár Pöllnitz provided medical writing support and Quentin Deraedt coordinated manuscript development and provided editorial support. The trials were funded by GlaxoSmithKline Biologicals SA, Rue de l'Institut 89, 1330 Rixensart, Belgium. GlaxoSmithKline Biologicals SA was involved in all stages of the conduct and analysis of the studies. GlaxoSmithKline Biologicals SA covered the costs associated with the development and the publishing of the present manuscript. Detailed authors’ contribution is provided in the supplementary materials.
Funding Information:
MLF, LC, FD, MEI and FTdS are employees, and LO, TCH and HL are former employees, of the GSK group of companies. FJDL reports receiving grant support from GSK and Novartis outside the submitted work. LO is an employee of CureVac AG. LO and TCH are inventors on a patent owned by GSK and relevant to RZV. JDD reports receiving personal fees from GSK for an advisory board on a pharmacoeconomic study with Synflorix in Spain, as well as grants and personal fees from Sanofi Pasteur MSD for an epidemiological study on herpes zoster and an advisory board on Zostavax, respectively, outside the submitted work. LO, TCH, HL and FTdS hold shares or stock options from GSK as part of their current or former employee remuneration. TCH served as a paid consultant to GSK outside the submitted work. HL is a current employee of Pfizer and receives stock as part of his employee remuneration. JEM reports receiving honoraria and fees paid to her institution from GSK, Sanofi Pasteur, Merck and Pfizer, as well as travel support from GSK, Sanofi Pasteur, Merck and Pfizer outside the submitted work. SAM reports research grant from Pfizer, personal fees for continuing professional development talks on adult immunization from Pfizer and Merck, and consulting fees from Pfizer and Merck outside the submitted work, as well as grant from GSK outside the submitted work. WY reports financial support from GSK to perform the study.
Publisher Copyright:
© 2019 GlaxoSmithKline Biologicals SA
PY - 2019/4/24
Y1 - 2019/4/24
N2 - Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV.
AB - Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV.
KW - Reactogenicity
KW - Safety
KW - Vaccine
KW - Varicella-zoster virus
UR - http://www.scopus.com/inward/record.url?scp=85063476515&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2019.03.043
DO - 10.1016/j.vaccine.2019.03.043
M3 - Article
C2 - 30935742
AN - SCOPUS:85063476515
SN - 0264-410X
VL - 37
SP - 2482
EP - 2493
JO - Vaccine
JF - Vaccine
IS - 18
ER -
