Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial

ABSTRACT

A quadrivalent high-dose inactivated influenza vaccine (IIV4-HD) is licensed for adults ≥65 y of age based on immunogenicity and efficacy studies. However, IIV4-HD has not been evaluated in adults aged 60–64 y. This study compared immunogenicity and safety of IIV4-HD with a standard-dose quadrivalent influenza vaccine (IIV4-SD) in adults aged ≥60 y. This Phase III, randomized, modified double-blind, active-controlled study enrolled 1,528 participants aged ≥60 y, randomized 1:1 to a single injection of IIV4-HD or IIV4-SD. Hemagglutination inhibition (HAI) geometric mean titers (GMTs) were measured at baseline and D 28 and seroconversion assessed. Safety was described for 180 d after vaccination. The primary immunogenicity objective was superiority of IIV4-HD versus IIV4-SD, for all four influenza strains 28 d post vaccination in participants aged 60–64 and ≥65 y. IIV4-HD induced a superior immune response versus IIV4-SD in terms of GMTs in participants aged 60–64 y and those aged ≥65 y for all four influenza strains. IIV4-HD induced higher GMTs in those aged 60–64 y than those aged ≥65 y. Seroconversion rates were higher for IIV4-HD versus IIV4-SD in each age-group for all influenza strains. Both vaccines were well tolerated in participants ≥60 y of age, with no safety concerns identified. More solicited reactions were reported with IIV4-HD than with IIV4-SD. IIV4-HD provided superior immunogenicity versus IIV4-SD and was well tolerated in adults aged ≥60 y. IIV4-HD is assumed to offer improved protection against influenza compared with IIV4-SD in adults aged ≥60 y, as was previously assessed for adults aged ≥65 y.

KEYWORDS:

• High-dose influenza vaccine
• influenza vaccination
• older adults
• immunogenicity
• safety
• Phase III trial

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Acknowledgments

The authors thank Niki Panagiotaki and Nick Tsimplis from Lucid Group Communications Ltd, Marlow, Buckinghamshire, UK for providing medical writing support, which was funded by Sanofi in accordance with Good Publication Practice (GPP3) guidelines. Responsibility for all opinions, conclusions, and interpretation of data lies with the authors. No author was paid for services involved in writing this manuscript. The QHD00011 study investigators included Isabel Leroux-Roels, Pierre Van Damme, Yves Donazzolo, Jean-François Nicolas, Odile Launay, Thomas Schürholz, Thomas Schaum, Kerstin Sturm, Nicole Toursarkissian, Isabelle Schenkenberger, Giancarlo Icardi, Francesco Vitale, Marc Bonten, Jerzy Brzostek, Barbara Pajek, Edyta Miszczak-Kowalska, and Henryk Szymanski. The Study Team included Rawia Khoury, Marie-Ange Grosbois, Corentin Gauby, Isabelle Lacroix, Fabienne Souzy, Aseem Pandey, Scott Yandle, Nicole Lupinsky, France Goulet, Laurence Milcamps, Jennifer De Sousa, Marine Lardon, Valerie Lyko, Arielle Blattmann, Helene Janosczyk, Sandrine Samson and Iris De Bruijn.

Disclosure statement

All authors acquired, analyzed, or interpreted data; drafted or critically revised the manuscript; approved the submitted version; and agreed to be accountable for its accuracy and integrity. In addition, SP and CT designed the study.

SP, AS, and CT are Sanofi Pasteur employees and may/may not hold stock/shares in the company.

MB reports fees paid to UMC Utrecht from Sanofi Pasteur, during the conduct of the study; fees paid to UMC Utrecht from Sanofi Pasteur, Janssen, and Pfizer, outside the submitted work. HS reports personal fees, nonfinancial support and other from Sanofi Pasteur during the conduct of the study; personal fees, nonfinancial support and other from Ablynx, GSK, Janssen, and Pfizer, outside the submitted work; also, personal fees and other from MSD and Seqirus, outside the submitted work.

IL-R reports fees paid to Ghent University Hospital from Sanofi Pasteur during the conduct of the study; fees paid to Ghent University Hospital from GSK, MSD, J&J and Curevac outside the submitted work. J-FN, TS, and GI have nothing to disclose.

Data availability statement

Qualified researchers may request access to patient-level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized and study documents will be redacted to protect the privacy of our trial participants. Further details on Sanofi’s data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2021.1983387

Additional information

Funding

The study was funded by Sanofi Pasteur.