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

Phase 3

Completed

Conditions: Healthy Volunteers
Influenza Immunization

Interventions: 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

Registration Number: NCT04024228

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1539

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2: QIV-SD	Standard-Dose influenza virus surface antigens (haemagglutinin and neuraminidase), Inactivated, Influenza Vaccine Quadrivalent, 2019-2020 Northern Hemisphere Strains (QIV-SD)	Participants received a single injection of 0.5 mL QIV-SD, IM at Day 0.
Group 1: QIV-HD	High-Dose Influenza Vaccine (split virion, inactivated), Quadrivalent (QIV-HD) 2019-2020 Northern Hemisphere formulation	Participants received a single injection of 0.7 milliliters (mL) QIV-HD, intramuscularly (IM) at Day 0.

Primary Outcome Measures

Name	Time	Method
Geometric Mean Titers (GMTs) of Influenza Antibodies in Participants Aged 60-64 Years and Greater Than or Equal to (>=) 65 Years	Day 28 post-vaccination	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.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Titers of Influenza Antibodies Pre-and Post-Vaccination in All Age Group Participants	Day 0 (pre-vaccination), Day 28 (post-vaccination)	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.
Geometric Mean Titers of Influenza Antibodies Pre- and Post-Vaccination in Participants Aged 60-64 Years and >=65 Years	Day 0 (pre-vaccination), Day 28 (post-vaccination)	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.
Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies in All Age Group Participants	Day 0 (pre-vaccination), Day 28 (post-vaccination)	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).
Geometric Mean Titer Ratios of Influenza Antibodies in Participants Aged 60-64 Years and >=65 Years	Day 0 (pre-vaccination), Day 28 (post-vaccination)	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).
Percentage of Participants (All Age Group Participants) With Neutralizing Antibody Titers >=40 (1/Dilution)	Day 28 post-vaccination	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.
Percentage of Participants (Aged 60-64 Years and >=65 Years) With Neutralizing Antibody Titers >=40 (1/Dilution)	Day 28 post-vaccination	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.
Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs)	Within 30 minutes post-vaccination	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.
Number of Participants Reporting Solicited Injection Site Reactions	Within 7 days post-vaccination	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.
Number of Participants Reporting Solicited Systemic Reactions	Within 7 days post-vaccination	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.
Number of Participants Reporting Unsolicited Adverse Events (AEs)	Within 28 days post-vaccination	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.
Number of Participants Reporting Serious Adverse Events (SAEs) Including Adverse Event of Special Interest (AESIs)	From Day 0 up to 6 months post-vaccination	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.
Percentage of Participants (All Age Group Participants) Achieving Seroconversion Against Antigens	Day 28 post-vaccination	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.
Percentage of Participants (Aged 60-64 Years and >=65 Years) Achieving Seroconversion Against Antigens	Day 28 post-vaccination	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.

Trial Locations

Locations (17): Investigational Site Number 0560002
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Wilrijk, Belgium
Investigational Site Number 2760003
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Berlin, Germany
Investigational Site Number 2500004
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Paris, France
Investigational Site Number 2760001
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Essen, Germany
Investigational Site Number 2760002
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Oldenburg In Holstein, Germany
Investigational Site Number 3800001
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Genova, Italy
Investigational Site Number 6160002
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Wola, Poland
Investigational Site Number 6160004
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Wroclaw, Poland
Investigational Site Number 0560001
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Gent, Belgium
Investigational Site Number 2760004
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Berlin, Germany
Investigational Site Number 2500003
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Pierre Benite Cedex, France
Investigational Site Number 6160001
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Debica, Poland
Investigational Site Number 2500001
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Gieres, France
Investigational Site Number 3800003
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Palermo, Italy
Investigational Site Number 5280001
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Utrecht, Netherlands
Investigational Site Number 6160003
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Siemianowice Slaskie, Poland
Investigational Site Number 2760005
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Berlin, Germany