Study of Recombinant Influenza Vaccine Containing Different H3 Antigens Without or With Adjuvant in Healthy Adult Subjects

Study Overview
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Brief Summary
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The primary objectives of the study are: To describe the safety profile of the different formulations in all participants To describe the hemagglutinin inhibition (HAI) and seroneutralization (SN) antibody responses against hemagglutinin (H1, H3, B/Victoria, and B/Yamagata) antigens present in the control vaccine in all groups at all timepoints. The secondary objectives are: To describe antigenic coverage in each group by assessing the HAI and SN antibody responses against a panel of H3 antigens (not present in any of the vaccine formulations). To describe SN antibody responses in each group against each of the H3 antigens. To compare H3 HAI and SN antibody responses for the groups with quadrivalent recombinant influenza vaccine (RIV) formulations with H3 antigens to those of the quadrivalent RIV control group. To compare the HAI and SN antibody responses for the groups with quadrivalent RIV formulation with adjuvant to the group without adjuvant.

Detailed Description
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Study duration per participant is approximately 1 year

Official Title
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Safety and Immunogenicity of Quadrivalent Recombinant Influenza Vaccine Formulations Containing Different H3 Hemagglutinin Antigens Without or With Adjuvant in Healthy Adult Subjects

Conditions
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Influenza Immunisation, Healthy Volunteers

Intervention / Treatment
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* Biological: Quadrivalent RIV with H3 strain 1
* Biological: Quadrivalent RIV with H3 strain 1 and adjuvant
* Biological: Quadrivalent RIV with H3 strain 2
* Biological: Quadrivalent RIV with H3 strain 2 and adjuvant
* Biological: Quadrivalent RIV with 2018-2019 NH H3 strain
* Biological: Quadrivalent RIV with 2018-2019 NH H3 strain and adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Older adults: Aged 50 years and older on the day of inclusion Young adults: Aged 18 to 30 years on the day of inclusion Informed consent form has been signed and dated Able to attend all scheduled visits and to comply with all trial procedures Exclusion criteria: Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 12 weeks postvaccination. To be considered of non-childbearing potential, a female must be premenarche, or postmenopausal for at least 1 year, or surgically sterile Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Receipt of any vaccine in the 4 weeks preceding the study vaccination or planned receipt of any vaccine in the 4 weeks following study vaccination Previous vaccination against influenza during either of the previous 2 influenza seasons (2018-2019 and 2019-2020) with any licensed or investigational influenza vaccine Receipt of immune globulins, blood, or blood-derived products in the past 3 months Known or suspected congenital or acquired immunodeficiency; immunosuppressive therapy (such as anticancer chemotherapy or radiation therapy, within the preceding 6 months); or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) or receipt of hydroxychloroquine within the preceding 4 weeks Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy History of influenza infection during either of the previous 2 influenza seasons (2018- 2019 or 2019-2020), confirmed by laboratory tests (including rapid tests) at that time History of laboratory confirmed coronavirus disease 2019 (COVID-19), confirmed with a nucleic acid amplification test on a respiratory specimen, or known exposure to severe acute respiratory syndrome coronavirus (SARS-CoV-2) positive confirmed close contact (eg, family member, housemate, daycare provider, aged parent requiring care), in the 30 days preceding vaccination, at the discretion of the investigator Self-reported or documented seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances Have any diagnosis, current or past, of an autoimmune disease Thrombocytopenia or bleeding disorder, contraindicating intramuscular vaccination based on investigator's judgment Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Any change in chronic prescription medication or change in medication dose or dosage in the 60 days prior to enrollment Alcohol abuse or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion Any current or past diagnosis of chronic pulmonary disease including asthma (history of childhood asthma is allowed), cystic fibrosis and chronic pulmonary obstructive disease Have taken a high-dose inhaled corticosteroid within 6 months prior to study vaccination Body mass index of 40 or higher Any current or past diagnosis of cardiac disease (eg, coronary artery disease, heart failure, or valvular heart disease [mild mitral valve prolapse allowed]). Participants with isolated primary (essential) hypertension are allowed Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (oral temperature ≥100.4 F [≥38.0 C]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided Identified as an investigator or employee of the investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the investigator or employee with direct involvement in the proposed study Personal or family history of Guillain-Barré syndrome History of chronic kidney disease Current or past diagnosis of thyroid disease (eg, thyroiditis [including Hashimoto's thyroiditis], hyperthyroidism, and hypothyroidism) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Group 1: Quadrivalent RIV with H3 strain 1, without adjuvant<br>1 injection of quadrivalent RIV containing H3 strain 1, without adjuvant, in participants ≥ 50 years old | Biological: Quadrivalent RIV with H3 strain 1<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 2: Quadrivalent RIV with H3 strain 1, with adjuvant<br>1 injection of quadrivalent RIV containing H3 strain 1, with adjuvant, in participants ≥ 50 years old | Biological: Quadrivalent RIV with H3 strain 1 and adjuvant<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 3: Quadrivalent RIV with H3 strain 2, without adjuvant<br>1 injection of quadrivalent RIV containing H3 strain 2, without adjuvant, in participants ≥ 50 years old | Biological: Quadrivalent RIV with H3 strain 2<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Experimental: Group 4: Quadrivalent RIV with H3 strain 2, with adjuvant<br>1 injection of quadrivalent RIV containing H3 strain 2, with adjuvant, in participants ≥ 50 years old | Biological: Quadrivalent RIV with H3 strain 2 and adjuvant<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 5: Quadrivalent RIV Control, without adjuvant<br>1 injection of quadrivalent RIV containing 2018-19 Northern Hemisphere (NH) recommended H3 strain, without adjuvant, in participants ≥ 50 years old | Biological: Quadrivalent RIV with 2018-2019 NH H3 strain<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 6: Quadrivalent RIV Control, with adjuvant<br>1 injection of quadrivalent RIV containing 2018-19 NH recommended H3 strain, with adjuvant, in participants ≥ 50 years old | Biological: Quadrivalent RIV with 2018-2019 NH H3 strain and adjuvant<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|
| Active Comparator: Group 7: Quadrivalent RIV Control, without adjuvant<br>1 injection of quadrivalent RIV containing 2018-19 NH recommended H3 strain, without adjuvant, in participants 18-30 years old | Biological: Quadrivalent RIV with 2018-2019 NH H3 strain<br>* Pharmaceutical form: Suspension for injection Route of administration: Intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with immediate adverse events | Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination | Within 30 minutes after vaccination | 
| Number of participants with solicited injection site or systemic reactions | Solicited injection site reactions: injection site pain, erythema, swelling, induration and bruising; solicited systemic reactions: fever, headache, malaise, and myalgia | From Day 0 to Day 7 | 
| Number of participants with unsolicited adverse events | Unsolicited (spontaneously reported) adverse events not not fulfilling criteria for solicited reactions | From Day 0 to Day 28 | 
| Number of participants with serious adverse events | Serious adverse events are collected throughout the study | From Day 0 to Day 365 | 
| Number of participants with adverse events of special interest | Adverse events of special interest are collected throughout the study | From Day 0 to Day 365 | 
| Clinical safety laboratory test results | Laboratory tests include complete blood count (CBC), platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, serum creatinine, serum lipase, and serum amylase) | From Day 0 to Day 7 | 
| HAI and SN antibody titers against influenza antigens in the quadrivalent RIV control vaccine | Influenza antibody titers are measured by HAI and SN assays | From Day 0 to Day 365 | 
| Individual HAI and SN titers ratio against influenza antigens in the quadrivalent RIV control vaccine | Titers ratio is calculated for the following time points: Day 7/Day 0, Day 28/Day 0, and Day 90/Day 0 | From Day 0 to Day 90 | 
| Number of participants with seroconversion to influenza antigens in the quadrivalent RIV control vaccine | Seroconversion is defined as HAI antibody titer < 10 [1/dil] at Day 0 and post-injection titer ≥ 40 [1/dil] at Day 28, or titer ≥ 10 [1/dil] at Day 0 and a ≥ 4-fold increase in titer [1/dil] at Day 28) | From Day 0 to Day 28 | 
| HAI Ab titer ≥ 40 [1/dil] | Influenza vaccine antibody titers are measured by HAI assay | From Day 0 to Day 365 | 
| 2-fold and 4-fold increase in SN titers | Influenza vaccine antibody titers are measured by SN assay | From Day 0 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAI antibody titers against influenza H3 antigens not present in the vaccine formulations and the SN antibody titers against each of the H3 antigens | Influenza vaccine antibody titers are measured by HAI and SN assays | Day 0, Day 7, Day 28, Day 90, Day 180, and Day 365 | 
| Individual HAI titer ratios against influenza H3 antigens not present in the vaccine formulations and individual SN titer ratio against each of the H3 antigens | Titer ratio is calculated for the following time points: Day 7/Day 0, Day 28/Day 0, Day 90/Day 0 | From Day 0 to Day 90 | 
| Number of participants with seroconversion to influenza H3 antigens not present in the vaccine formulations | Seroconversion is defined as HAI antibody titer < 10 [1/dil] at Day 0 and post-injection titer ≥ 40 [1/dil] at Day 28, or titer ≥ 10 [1/dil] at Day 0 and a ≥ 4-fold increase in titer [1/dil] at Day 28) | Day 0 and Day 28 | 
| 2-fold and 4-fold rise in SN antibody titers against each of the H3 antigens | Influenza vaccine antibody titers a are measured by SN assay | Day 0, Day 7, Day 28, Day 90, Day 180, and Day 365 |