Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Patients ≥65 Years

Study Overview
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Brief Summary
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This phase I/II, randomized, modified double-blind, multi-center study assessed the safety and immunogenicity of a high-dose Quadrivalent influenza vaccine (QIV-HD) in older adults (greater than or equal to [>=] 65 years).

Detailed Description
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This phase I/II, randomized, modified double-blind, multi-center study was conducted in 175 healthy Japanese adults aged 65 years and older to describe the safety profile and immune responses (geometric mean titers and seroconversion for the 4 common strains at 28 days post-vaccination) of the QIV-HD administered by intramuscular (IM) and subcutaneous (SC) methods. A local standard-dose Quadrivalent Influenza Vaccine (QIV-SD) administered by SC method served as a control arm.

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

Conditions
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Influenza

Intervention / Treatment
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* Biological: QIV-HD by IM
* Biological: QIV-SD by SC
* Biological: QIV-HD by SC


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 has been signed and dated. Able to attend all scheduled visits and to comply with all study procedures. Exclusion Criteria: 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 vaccination with live vaccines within the past 27 days preceding the study vaccination or any vaccination with inactivated vaccines within the past 6 days preceding the study vaccination, or planned receipt of any vaccine prior to Visit 3. Previous vaccination against influenza (in the preceding 6 months) with either the study 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 eggs, chicken proteins, or any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the study 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 study conduct or completion. Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion. 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 (i.e., 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 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 >=37.5°Celsius). A prospective participant were not be included in the study until the condition had resolved or the febrile event had subsided. History of convulsions.

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: Sequential Assignment
Interventional Model Description: Safety and tolerability was initially assessed in the first 10 participants in a smaller cohort (Cohort 1). Participants were randomized 1:1 into 2 groups in Cohort 1: QIV-HD by IM route (n=5) and QIV-HD by SC route (n=5). After review of the local and systemic adverse events, the remaining 165 participants were enrolled (Cohort 2). Participants were randomized 1:1:1 into 3 groups in Cohort 2: QIV-HD by IM route (n=55), QIV-HD by SC route (n=55), and QIV-SD by SC route (n=55).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: QIV-HD by IM<br>Participants were randomized to receive a single 0.7-milliliter (mL) injection of QIV-HD by IM route on Day 0. | Biological: QIV-HD by IM<br>* IM, injected into the upper arm (deltoid area)<br>* Other names: High-Dose Influenza Vaccine Quadrivalent (IM);|
| Experimental: Cohort 1: QIV-HD by SC<br>Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. | Biological: QIV-HD by SC<br>* SC, injection into the upper arm (posterior region)<br>* Other names: High-Dose Influenza Vaccine Quadrivalent (SC);|
| Experimental: Cohort 2: QIV-HD by IM<br>Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. | Biological: QIV-HD by IM<br>* IM, injected into the upper arm (deltoid area)<br>* Other names: High-Dose Influenza Vaccine Quadrivalent (IM);|
| Experimental: Cohort 2: QIV-HD by SC<br>Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. | Biological: QIV-HD by SC<br>* SC, injection into the upper arm (posterior region)<br>* Other names: High-Dose Influenza Vaccine Quadrivalent (SC);|
| Active Comparator: Cohort 2: QIV-SD by SC<br>Participants were randomized to receive a single 0.5 mL injection of QIV-SD by SC route on Day 0. | Biological: QIV-SD by SC<br>* SC, injected into the upper arm (posterior region)<br>* Other names: Standard-Dose Influenza Vaccine Quadrivalent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Immediate Unsolicited Adverse Events (AE) After Vaccination | An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of symptom and/or onset post-vaccination. Unsolicited AEs includes both serious and non-serious unsolicited AEs. A serious adverse event is 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, is a congenital anomaly/birth defect, or is an important medical event. 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 after vaccination | 
| Number of Participants With Solicited Injection Site and Systemic Reactions | A solicited reaction was an adverse reaction observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions: pain, erythema, swelling, induration, and bruising. Solicited systemic reactions: fever, headache, malaise, myalgia, and shivering. | Within 7 days after vaccination | 
| Number of Participants With Unsolicited Adverse Events After Vaccination | An unsolicited AE was an observed AE that does 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 is 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, is a congenital anomaly/birth defect, or is an important medical event. | Within 28 days after vaccination | 
| Number of Participant With Serious Adverse Events (SAEs) After Vaccination | An SAE is 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, is a congenital anomaly/birth defect, or is an important medical event. | Up to 6 months after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 2: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD | GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using a hemagglutination inhibition (HAI) assay. | Day 0 (pre-vaccination) and Day 28 (post-vaccination) | 
| Cohort 2: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD | GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using an HAI assay. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination. | Day 0 (pre-vaccination) and Day 28 (post-vaccination) | 
| Cohort 2: Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With QIV-HD or QIV-SD | Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroconversion was defined as either a HAI titer lesser than (<) 10 (1/dilution) at Day 0 and post-vaccination 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. | Day 28 (post-vaccination) | 
| Cohort 2: Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With QIV-HD or QIV-SD | Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. 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) | 

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