Study to Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Europeans Adults 60 Years of Age and Older

Study Overview
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Brief Summary
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Primary Objective: To demonstrate that high-dose quadrivalent influenza vaccine (QIV-HD) induces an immune response that is superior to the responses induced by standard-dose quadrivalent influenza vaccine (QIV-SD) for all 4 virus strains 28 days post-vaccination in participants 60 to 64 years of age and in participants 65 years of age and older. Secondary Objective: Immunogenicity: To further describe the immune response induced by QIV-HD and QIV-SD in all participants by age group, in pooled age groups, and by vaccine group (QIV-HD; QIV-SD). Safety: To describe the safety profile of all participants by age group, in pooled age groups, and by vaccine group (QIV-HD; QIV-SD).

Detailed Description
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Study duration per participant was approximately 6 months including: 1 day of screening and vaccination, an end of study visit and safety follow-up telephone call approximately at Day 28 and Day 180 after vaccination, respectively.

Official Title
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Immunogenicity and Safety of a High-Dose Quadrivalent Influenza Vaccine Administered by the Intramuscular Route in Subjects 60 Years of Age and Older

Conditions
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Influenza Immunization, Healthy Volunteers

Intervention / Treatment
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* Biological: Standard-Dose influenza virus surface antigens (haemagglutinin and neuraminidase), Inactivated, Influenza Vaccine Quadrivalent, 2019-2020 Northern Hemisphere Strains (QIV-SD)
* Biological: High-Dose Influenza Vaccine (split virion, inactivated), Quadrivalent (QIV-HD) 2019-2020 Northern Hemisphere formulation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Sixty years of age and older on the day of inclusion. Able to attend all scheduled visits and complied with all trial procedures. Exclusion criteria: Participant was pregnant, or lactating, or of childbearing potential and did not used an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile. Participation at the time of study enrollment (or in the 4 weeks [28 days] preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 02. Previous vaccination against influenza (in the previous 6 months) with either the trial vaccine or another vaccine. Receipt of immune globulins, blood or blood-derived products in the past 3 months. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer 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). Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances. Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgement. Alcohol or substance abuse that, in the opinion of the Investigator might interfere with the trial conduct or completion. Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion Moderate or severe acute illness/infection (according to Investigator judgment) or febrile illness (temperature greater than or equal to (>=) 38.0 degree Celsius) on the day of vaccination. A prospective participant should not be included in the study until the condition had resolved or the febrile event had 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. Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that was stable at the time of vaccination in the absence of therapy and participants who had a history of neoplastic disease and had been disease free for >= 5 years) The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 60 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
Interventional Model Description: Participants randomized in each group were stratified by age (60 to 64 years of age; 65 years of age and older).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: QIV-HD<br>Participants received a single injection of 0.7 milliliters (mL) QIV-HD, intramuscularly (IM) at Day 0. | Biological: High-Dose Influenza Vaccine (split virion, inactivated), Quadrivalent (QIV-HD) 2019-2020 Northern Hemisphere formulation<br>* Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM<br>|
| Active Comparator: Group 2: QIV-SD<br>Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0. | Biological: Standard-Dose influenza virus surface antigens (haemagglutinin and neuraminidase), Inactivated, Influenza Vaccine Quadrivalent, 2019-2020 Northern Hemisphere Strains (QIV-SD)<br>* Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM<br>* Other names: Influvac™ Tetra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Influenza Antibodies in Participants Aged 60-64 Years and Greater Than or Equal to (>=) 65 Years | GMTs of anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage).Titers were expressed in terms of 1/dilution. | Day 28 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Influenza Antibodies Pre-and Post-Vaccination in All Age Group Participants | GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage).Titers were expressed in terms of 1/dilution. | Day 0 (pre-vaccination), Day 28 (post-vaccination) | 
| Geometric Mean Titers of Influenza Antibodies Pre- and Post-Vaccination in Participants Aged 60-64 Years and >=65 Years | GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Titers were expressed in terms of 1/dilution. | Day 0 (pre-vaccination), Day 28 (post-vaccination) | 
| Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies in All Age Group Participants | GMTRs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). GMTRs were calculated as the ratio of GMTs post-vaccination (on Day 28) and pre-vaccination (on Day 0). | Day 0 (pre-vaccination), Day 28 (post-vaccination) | 
| Geometric Mean Titer Ratios of Influenza Antibodies in Participants Aged 60-64 Years and >=65 Years | GMTRs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). GMTRs were calculated as the ratio of GMTs post-vaccination (on Day 28) and pre-vaccination (on Day 0). | Day 0 (pre-vaccination), Day 28 (post-vaccination) | 
| Percentage of Participants (All Age Group Participants) With Neutralizing Antibody Titers >=40 (1/Dilution) | Neutralizing Antibody titer was measured using HAI assay method for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Percentage of participants (all age group participants) with neutralizing antibody titers >=40 (1/dilution) is reported in the outcome measure. | Day 28 post-vaccination | 
| Percentage of Participants (Aged 60-64 Years and >=65 Years) With Neutralizing Antibody Titers >=40 (1/Dilution) | Neutralizing Antibody titer was measured using HAI assay method for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Percentage of participants (aged 60-64 Years and >=65 Years) with neutralizing antibody titers >=40 (1/dilution) is reported in the outcome measure. | Day 28 post-vaccination | 
| Percentage of Participants (All Age Group Participants) Achieving Seroconversion Against Antigens | Anti-influenza antibodies were measured by HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Seroconversion was defined as either a pre-vaccination HAI titer less than (<) 1:10 (1/dilution) and a post-vaccination titer >=1:40 (1/dilution) or a pre-vaccination titer >= 1:10 (1/dilution) and a >= four-fold increase in post-vaccination titer at Day 28. Percentage of participants (all age group participants) achieving seroconversion is reported in the outcome measure. | Day 28 post-vaccination | 
| Percentage of Participants (Aged 60-64 Years and >=65 Years) Achieving Seroconversion Against Antigens | Anti-influenza antibodies were measured by HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B1 (B Victoria lineage), and B2 (B Yamagata lineage). Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 (1/dilution) and a post-vaccination titer >= 1:40 (1/dilution) or a pre-vaccination titer >= 1:10 (1/dilution) and a >= four-fold increase in post-vaccination titer at Day 28. Percentage of participants (aged 60-64 Years and >=65 Years) achieving seroconversion is reported in the outcome measure. | Day 28 post-vaccination | 
| Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs) | An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not had any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. | Within 30 minutes post-vaccination | 
| Number of Participants Reporting Solicited Injection Site Reactions | A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the product administered. Solicited injection site reactions included induration, bruising, pain, erythema, and swelling. | Within 7 days post-vaccination | 
| Number of Participants Reporting Solicited Systemic Reactions | A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the product administered. Solicited systemic reactions included fever, headache, malaise, myalgia and shivering. | Within 7 days post-vaccination | 
| Number of Participants Reporting Unsolicited Adverse Events (AEs) | An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not had any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. | Within 28 days post-vaccination | 
| Number of Participants Reporting Serious Adverse Events (SAEs) Including Adverse Event of Special Interest (AESIs) | A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. A SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) was defined as event for which ongoing monitoring and rapid communication by the investigator to the sponsor was done. | From Day 0 up to 6 months post-vaccination |