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

Study Overview
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Brief Summary
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This is a Phase 3, randomized, parallel-group, comparator-controlled, observer-blind, multicenter study of immunogenicity and safety in approximately 7700 male and female adults aged 50 years and older (approximately equally split between two age groups: 50-64 years; 65 years and older), who are healthy or have stable comorbidities that increase their risk of complications from influenza infection. Three lots of aQIVc will be evaluated for consistency and pooled for the comparison with the 2 control vaccines. Subjects will be randomly assigned to receive 1 of 3 lots of aQIVc, QIV1, or QIV2 in a 1:1:1:2:2 ratio (for a 3:2:2 ratio for aQIVc, QIV1, and QIV2). The study will have a treatment period (Day 1 to Day 29) and a follow-up period (Day 30 up to Day 181); a subset of 770 subjects will be followed up up to Day 365.

Official Title
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A Phase 3, Randomized, Observer-Blind, Controlled, Multicenter, Clinical Study to Evaluate Immunogenicity and Safety of a MF59-Adjuvanted Quadrivalent Subunit Cell-derived Influenza Vaccine (aQIVc) in Comparison With Quadrivalent Influenza Vaccines, in Adults Aged 50 Years and Older.

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: Investigational aQIVc
* Biological: licensed QIV1
* Biological: licensed QIV2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational aQIVc group<br> | Biological: Investigational aQIVc<br>* Investigational MF59 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.<br>|
| Active Comparator: licensed QIV1 group<br> | Biological: licensed QIV1<br>* Licensed, Quadrivalent Influenza Vaccine 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.<br>|
| Active Comparator: licensed QIV2 group<br> | Biological: licensed QIV2<br>* Licensed, Quadrivalent Influenza Vaccine 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. | Day 29 | 
| Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIV1 and QIV2 vaccines in terms of Day 29 GMT and GMT ratio of antibodies measured via HI assay. | 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 (QIV1 or QIV2) 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. | Day 29 | 
| Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIV1 and QIV2 vaccines in terms of Day 1 to Day 29 SCR and SCR difference, from antibody titers measured via HI assay. | 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 (QIV1 or QIV2) 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. | Day 1 and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIV1 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. | 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 HD/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 HD minus comparator) is ≥-10% for each of the 4 vaccine strains. | Day 1 and Day 29 | 
| Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIV1 and QIV2 vaccines in terms of Day 29 GMT and GMT ratio of antibodies measured via HI assay. | 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 (QIV1 and QIV2) 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. | Day 29 | 
| Immunogenicity Endpoints: For aQIVc, QIV1, and QIV2 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. | 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. | Day 1 and Day 29 | 
| Immunogenicity Endpoints: For aQIVc and QIV1 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. | 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. | Day 1 and Day 29 | 
| Immunogenicity Endpoints: For aQIVc, QIV1 and QIV2 vaccines, GMT, GMFI, Percentage of subjects with HI titer ≥1:40, SCR, SCR differences, and GMT ratio of antibodies measured via HI assay. | 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. | Day 1 up to Day 365 | 
| Immunogenicity Endpoints: For aQIVc, QIV1 and QIV2 vaccines, GMT, GMFI, SCR, SCR difference, and GMT ratio of antibodies measured via MN assay. | 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. | Day 1 up to Day 365 | 
| Safety endpoints: For aQIVc, QIV1 and QIV2 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, QIV1 and QIV2 vaccines, the percentage of Subjects with Unsolicited Adverse Events. |  | Day 1 to Day 29 | 
| Safety endpoints: For aQIVc, QIV1 and QIV2 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, QIV1 and QIV2 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). | Long-term safety for the long-term subset of 770 subjects | Day 1 to Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, vaccine, MF59, Adjuvant