The Celljuvant Study: A Phase 3 Immunogenicity and Safety Study of aQIVc Vaccine in Adults Aged 50 Years and Older

• Investigational aQIVc (Biological): Investigational Adjuvanted Cell-derived Quadrivalent Influenza vaccine, containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
• licensed QIVr (Biological): Recombinant Quadrivalent Influenza Vaccine (Flublok Quadrivalent/Supemtek) containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO for quadrivalent vaccines for the respective season.
• licensed aQIV (Biological): Adjuvanted, egg-derived Quadrivalent Influenza Vaccine (Fluad) containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO for quadrivalent vaccines for the respective season.

Primary outcomes

• Immunogenicity Endpoint: Humoral immune responses of 3 lots of aQIVc compared in pairs in terms of Day 29 GMT ratio between each pair among the 3 lots, from antibody titers measured via HI assay. [Day 29]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains.
• Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIVr and aQIV vaccines in terms of Day 29 GMT and GMT ratio of antibodies measured via HI assay. [Day 29]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. Noninferiority of aQIVc versus comparator (QIVr or aQIV) will be demonstrated if the lower limit (LL) of the 2-sided 97.5% CI for the Day 29 GMT ratio (aQIVc/comparator) is ≥0.67 for each of the 4 vaccine strains.
• Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIVr and aQIV vaccines in terms of Day 1 to Day 29 SCR and SCR difference, from antibody titers measured via HI assay. [Day 1 and Day 29]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. SCR is the percentage of subjects with seroconversion (defined as either a prevaccination \[Day 1\] titer <1:10 and a postvaccination \[Day 29\] titer ≥1:40, or a prevaccination titer ≥1:10 and a ≥4-fold increase in postvaccination titer). Noninferiority of aQIVc versus comparator (QIVr or aQIV) will be demonstrated if the lower limit (LL) of the 2-sided 97.5% CI for the difference in SCR (aQIVc minus comparator) is ≥-10% for each of the 4 vaccine strains.

Secondary outcomes

• Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with aQIV vaccine in terms of Day 29 SCR and SCR difference, GMT and GMT ratio of antibodies measured via HI assay in subjects 65 years and older. [Day 1 and Day 29]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. Noninferiority will be demonstrated if the LL of the 2-sided adjusted CI for the Day 29 GMT ratio (aQIVc/comparator) is ≥0.67 for each of the 4 vaccine strains, and the LL of the 2-sided adjusted CI for the difference in SCR (aQIVc minus comparator) is ≥-10% for each of the 4 vaccine strains.
• Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIVr and aQIV vaccines in terms of Day 29 GMT and GMT ratio of antibodies measured via HI assay. [Day 29]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. Superiority of aQIVc versus comparator (QIVr and aQIV) will be demonstrated if the LL of the 2-sided 97.5% CI for the inter-group GMT ratio (aQIVc/comparator) is >1.0 for each of the 4 vaccine strains.
• Immunogenicity Endpoints: For aQIVc, QIVr, and aQIV vaccines, Day 29 GMT, Day 1 to Day 29 GMFI, Percentage of subjects with HI titer ≥1:40 at Day 29, Day 1 to Day 29 SCR, SCR differences and GMT ratio of antibodies measured via HI assay. [Day 1 and Day 29]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains, overall and by age subgroup.
• Immunogenicity Endpoints: For aQIVc and aQIV vaccines, Day 29 GMT, Day 1 to Day 29 GMFI, Percentage of subjects with HI titer ≥1:40 at Day 29, Day 1 to Day 29 SCR, SCR differences, and GMT ratio of antibodies measured via HI assay. [Day 1 and Day 29]: HI assay will be measured using egg-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains in the HI-egg subset of 2750 subjects, overall and by age subgroup.
• Immunogenicity Endpoints: For aQIVc, QIVr and aQIV vaccines, GMT, GMFI, Percentage of subjects with HI titer ≥1:40, SCR, SCR differences, and GMT ratio of antibodies measured via HI assay. [Day 1 up to Day 365]: HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains in the long-term subset of 770 subjects, overall and by age subgroup.
• Immunogenicity Endpoints: For aQIVc, QIVr and aQIV vaccines, GMT, GMFI, SCR, SCR difference, and GMT ratio of antibodies measured via MN assay. [Day 1 up to Day 365]: MN assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains in the long-term subset of 770 subjects, overall and by age subgroup.
• Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentages of Subjects with Solicited Local Adverse Events, Solicited Systemic Adverse Events, and Severe Solicited Local and/or Systemic AEs. [Day 1 to Day 7]
• Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentage of Subjects with Unsolicited Adverse Events. [Day 1 to Day 29]
• Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentages of subjects with Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and non-serious Medically Attended Adverse Events (MAAEs). [Day 1 to Day 181]
• Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentages of subjects with Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and non-serious Medically Attended Adverse Events (MAAEs). [Day 1 to Day 365]: Long-term safety for the long-term subset of 770 subjects

Sex: All, ages: 50 Years to any, accepts healthy volunteers

Main Inclusion Criteria:

* Individuals, aged 50 years and older, who are healthy or have stable comorbidities that increase their risk of complications from influenza infection
* Individuals who can comply with all study procedures

Main Exclusion Criteria:

* Progressive, unstable, or uncontrolled clinical conditions
* Known hypersensitivity or allergy to any study vaccine component
* Known history of Guillain-Barré syndrome or other demyelinating disease
* Condition representing a contraindication to vaccination or blood draw
* Abnormal function of immune system due to known disorder or medication.
* Influenza vaccination within 180 days prior to informed consent.

• Results publication: Essink BJ, Vermeulen W, Andrade C, Mazur M, de Rooij R, Heijnen E, Casula D, Xing R, Tovar MP, Garner V, Albano FR. Immunogenicity and safety of an MF59-adjuvanted cell-derived higher-dose quadrivalent influenza vaccine (aQIVc) in adults aged 50 years or older: a phase 3 randomised controlled trial. Lancet Infect Dis. 2026 Sep 10:S1473-3099(26)00410-X. doi: 10.1016/S1473-3099(26)00410-X. Online ahead of print. PMID 42721997
• Results publication: de Looze F, Essink BJ, van Boxmeer J, Andrade C, de Rooij R, Casula D, Xing R, Tovar MP, Albano FR. Immunogenicity and safety of higher-dose cell-based adjuvanted quadrivalent influenza vaccines: Combined results of randomised, controlled dose-finding and dose-confirmation studies. Vaccine. 2026 Apr 19;79:128436. doi: 10.1016/j.vaccine.2026.128436. Epub 2026 Mar 19. PMID 41855648

• Clinical Program Director, Study director, Seqirus