Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Participants ≥65 Years in the US

Study Overview
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Brief Summary
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This randomized, modified double-blind, active-controlled, multi-center trial assessed the safety and immunogenicity of the high-dose quadrivalent influenza vaccine (QIV-HD) compared to either the licensed or investigational high-dose trivalent influenza vaccine (TIV-HD) in adults.

Detailed Description
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This randomized, modified double-blind, active-controlled, multi-center trial was conducted in healthy adults (greater than and equal to [>=] 65 years) to assess the safety and immunogenicity (geometric mean titers and seroconversion for the 4 virus strains at 28 days post vaccination) of the QIV-HD compared to one of the TIV-HDs containing either the B strain from the primary lineage (TIV-HD1; licensed vaccine [Fluzone® High-Dose] for the 2017-2018 Northern Hemisphere [NH] influenza season) or the B strain from the alternate lineage (TIV-HD2, investigational TIV-HD containing an alternate B strain).

Official Title
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Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Participants Aged 65 Years and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: QIV-HD
* Biological: Licensed TIV-HD1
* Biological: Investigational TIV-HD2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged >= 65 years on the day of inclusion. Informed consent form had been signed and dated. Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Participation at the time of trial enrollment (or in the 4 weeks 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 2. Previous vaccination against influenza (in the preceding 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 judgment. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. 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. Identified as an Investigator or employee of the Investigator or trial center with direct involvement in the proposed trial, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed trial. Personal or family history of Guillain-Barré syndrome. Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy and participants who have a history of neoplastic disease and have been disease free for >= 5 years). Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0°C [>= 100.4°F]). A prospective participant should not be included in the trial until the condition has resolved or the febrile event had subsided.

Ages Eligible for Study
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Minimum Age: 65 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: QHD00013 was a phase III, randomized, modified double-blind, active-controlled, multi-center trial.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QIV-HD<br>Participants randomized to receive a single injection of 0.7 mL QIV-HD by intramuscular (IM) route at Day 0. | Biological: QIV-HD<br>* 0.7 mL-dose was administered intramuscularly (IM) into the upper arm area.<br>* Other names: High-dose quadrivalent influenza vaccine;|
| Active Comparator: TIV-HD1 (Licensed TIV-HD1)<br>Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0. | Biological: Licensed TIV-HD1<br>* 0.5 mL-dose was administered IM into the upper arm area.<br>* Other names: High-dose trivalent influenza vaccine;|
| Active Comparator: TIV-HD2 (Investigational TIV-HD2)<br>Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0. | Biological: Investigational TIV-HD2<br>* 0.5 mL-dose was administered IM into the upper arm area.<br>* Other names: High-dose trivalent influenza vaccine (alternate B strain);|

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 Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | GMTs of anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain. | Day 28 post-vaccination | 
| Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Seroconversion was defined as either a HAI titer less than (<) 10 (1/dilution) at Day 0 and post-injection titer greater than or equal to (>=) 40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain. | Day 28 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). For each B strain, the immunogenicity of QIV-HD was compared to that of TIV-HD group which contains the corresponding B strain. TIV-HD1 did not contain B2 strain; TIV-HD2 did not contain B1 strain. | Day 28 post-vaccination | 
| GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | GMTs of anti-influenza antibodies using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Geometric Mean Titers Ratios (GMTRs) were calculated as the ratio of GMTs post vaccination and pre-vaccination. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Percentage of Participants Achieving Seroconversion Against Antigens of B Strains After Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | Seroconversion was defined as either a HAI titer <10 (1/dilution) at Day 0 and post-injection titer >=40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. | Day 28 post-vaccination | 
| Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Geometric Mean Titers of Influenza Antibodies (Seroneutralization [SN] Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | GMTs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | GMTRs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 | Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Neutralizing antibody was defined as titers >=20 (1/dilution), >=40 (1/dilution), >=80 (1/dilution) at Day 0 and Day 28. | Day 0, Day 28 | 
| Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 | Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / baseline computed value. | Day 28 | 
| Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 | Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Detectable neutralization antibody titer >= 1:10 (1/dilution) at Day 0 and Day 28. | Day 0, Day 28 | 
| Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine | Solicited injection site: Pain, Erythema, Swelling, Induration, and Bruising. Grade 3 reactions: Pain - interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention; Erythema, Swelling, Induration, and Bruising: >100 millimeters (mm). Systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 reactions: Fever: >=39°C; Headache, Malaise, Myalgia, and Shivering: interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. | Within 7 days after vaccination | 
| Number of Participants With Immediate Adverse Event (AEs) | Participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurring during that time was recorded as immediate unsolicited systemic AEs (AEs that were related to the investigational product) in the case report book (CRB). Unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/ or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. | Within 30 minutes after vaccination | 
| Number of Participant With Unsolicited Adverse Event (AE) | An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. | Within 28 days after vaccination | 
| Number of Participant With Serious Adverse Event | An serious adverse event was any untoward medical occurrence that at any dose results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect, or was an important medical event. | Up to 6 months after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza