Adjuvanted Seasonal Recombinant Quadrivalent Virus-Like Particles (QVLP) Influenza Vaccine in Adults 65 Years of Age and Older

Medicago209 enrolled

Overview

This randomized, partially-blinded, active comparator-controlled was conducted at multiple sites globally. The composition of QVLP used in this study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs and is based on the 2020-2021 influenza virus strains. In this study, 3 dose levels (15 μg/strain, 30 μg/strain, and 45 μg/strain) of QVLP were planned to be tested in combination with 2 dose levels of AS03 adjuvant (full and half dose) in a single-dose regimen to select a dose level of QVLP and adjuvant dose level-combination that is safe and effective for further development. Participants participated in this study for up to approximately 13 months, during which the first visit was scheduled for screening (up to 7 days in advance of vaccine administration) and the second visit on Day 0 was scheduled for vaccine administration. Telephone contacts were made on Day 1, Day 8, and monthly (starting after Day 28) until the end of the study for safety assessments, including concomitant medication use review. Blood draws at the clinic site for key safety assessments were made on Day 3, and Day 28 and for key immunogenicity assessments on Day 0, Day 28, Day 182 (6-month follow-up), and Day 365 (12-month follow-up).

In this study, a partially-blinded design was applied whereby the following individuals did not have access to treatment allocation (i.e. remained "blind") throughout the entire study duration: the participants, the Investigators and all personnel involved in the clinical conduct of the study (except the staff involved in the preparation and administration of the study vaccine, the quality assurance auditor, and quality control reviewers), Medicago clinical staff and medical staff involved in safety evaluations (e.g. causality assessments), and all personnel involved in sample analysis at the central and testing laboratories. A total of 209 participants were randomized to the study, divided into 8 groups receiving different adjuvant dose level-combinations of QVLP or Fluzone HD Quad (60 µg/strain). The majority of participants (126 participants) received QVLP 30 μg/strain with full dose AS03 (42 participants), QVLP 30 μg/strain unadjuvanted (41 participants) or Fluzone HD Quad (43 participants), while in 5 other groups with 83 participants enrolled in total the enrollment was discontinued prematurely due to recruitment challenges caused by COVID-19 pandemic.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants read, understood, and signed the informed consent form prior to participating in the study; participants also completed study-related procedures and communicated with the study staff at visits and by phone during the study; 2. Male and female participants 65 years of age and older at the Vaccination visit (Visit 2); 3. Participants had a body mass index (BMI) \< 30 kg/m2 at the Vaccination visit (Visit 2); 4. Participants were considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study; 5. Participants were non-institutionalized (e.g. not living in rehabilitation centers or old-age homes; living in an elderly community was acceptable) and had no acute or evolving medical problems prior to study participation and no clinically relevant abnormalities that could jeopardize participant safety or interfere with study assessments, as assessed by the Investigator and determined by medical history, physical examination, serology, clinical chemistry and hematology tests, urinalysis, and vital signs. Investigator discretion was permitted with this inclusion criterion; Note: Participants with a pre-existing chronic disease were allowed to participate if the disease was stable and, according to the Investigator's judgment, the condition was unlikely to confound the results of the study or pose additional risk to the participant by participating in the study. Stable disease was generally defined as no new onset or exacerbation of pre-existing chronic disease 3 months prior to vaccination. Based on the Investigator's judgment, participants with more recent stabilization of a disease were also eligible. Exclusion Criteria: 1. According to the Investigator's opinion, significant acute or chronic, uncontrolled medical or neuropsychiatric illness. Acute disease was defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Vaccination visit (Visit 2). "Uncontrolled" was defined as: * Requiring a new medical or surgical treatment during the 3 months prior to study vaccine administration; * Required any significant change in a chronic medication (i.e. drug, dose, frequency) during the 3 months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change met the criteria outlined in inclusion criterion #5 and was appropriately justified and documented by the Investigator. Note: Investigator discretion was permitted with this exclusion criterion. 2. Any confirmed or suspected current immunosuppressive condition or immunodeficiency, including cancer, human immunodeficiency virus, hepatitis B or C infection (participants with a history of cured hepatitis B or C infection without any signs of immunodeficiency at present time were allowed). Investigator discretion was permitted with this exclusion criterion; 3. Current autoimmune disease requiring systemic treatment (such as rheumatoid arthritis, systemic lupus erythematosus, or multiple sclerosis). Investigator discretion was permitted with this exclusion criterion, and participants were eligible to participate with appropriate written justification in the source document (i.e. participants with a history of autoimmune disease who were disease-free without treatment for 3 years or more, or on stable thyroid replacement therapy, mild psoriasis \[i.e. a small number of minor plaques requiring no systemic treatment\], etc.); 4. Administration of any non-influenza vaccine within 30 days prior to the Vaccination visit (Visit 2); planned administration of any vaccine up to Day 28 of the study. Immunization on an emergency basis during the study was evaluated on case-by-case basis by the Investigator. Note: Administration of an authorized COVID-19 vaccine prior to or during the study was acceptable; 5. Administration of influenza vaccine within 6 months prior to the Vaccination visit (Visit 2) or planned administration of influenza vaccine (other than the study vaccine) up to completion of the study; 6. Administration of any adjuvanted or investigational influenza vaccine within 1 year prior to randomization or planned administration prior to the completion of the study; 7. Use of any investigational or non-registered product within 30 days or five half-lives, whichever is longer, prior to the Vaccination visit (Visit 2) or planned use during the study period. Participants who were in a prolonged post-administration observation period of another investigational or marketed drug clinical study, for which there was no ongoing exposure to the investigational or marketed product and all scheduled on-site visits were completed, were allowed to take part in this study, if all other eligibility criteria were met; 8. Administration of any medication or treatment that may alter the vaccine immune responses, such as: * Systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than 7 consecutive days or for 10 or more days in total, within 1 month prior to the Vaccination visit (Visit 2). Inhaled, nasal, intraarticular, ophthalmic, dermatological, and other topical glucocorticoids were permitted; * Cytotoxic, antineoplastic or immunosuppressant drugs - within 36 months prior to the Vaccination visit (Visit 2); * Any immunoglobulin preparations or blood products, blood transfusion - within 6 months prior to the Vaccination visit (Visit 2); 9. Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, including those that were thought to be effective for prevention of COVID-19 but had not been licensed for this indication, within 1 month prior to the Vaccination visit (Visit 2); 10. Participants at high risk of contracting SARS-CoV-2/COVID-19 infection, including, but not limited to, individuals with known close contact with: * anyone residing in, visiting, or working at a health care or long-term care institution (i.e. long-term care facilities, acute care hospitals, rehabilitation hospitals, mental health hospitals, emergency departments); * anyone with laboratory-confirmed SARS-CoV-2/COVID-19 infection within 2 weeks prior to vaccine administration; * anyone who traveled outside the country for any duration within 30 days before the study vaccination; 11. History of allergy to any of the constituents of QVLP, any components of Fluzone HD Quad, the adjuvant AS03, egg, or tobacco; 12. History of anaphylactic allergic reactions to plants or plants components (including fruits and nuts); 13. Participants with a history of Guillain-Barré Syndrome; 14. Personal or family (first-degree relatives) history of narcolepsy; 15. Use of prophylactic medications (e.g. antihistamines \[H1 receptor antagonists\], nonsteroidal anti-inflammatory drugs \[NSAIDs\], systemic and topical glucocorticoids, non-opioid and opioid analgesics) within 24 hours prior to the Vaccination visit (Visit 2) to prevent or pre-empt symptoms due to vaccination; 16. Had a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that could interfere with injection site reaction rating. Investigator discretion was permitted with this exclusion criterion; 17. Participants identified as an Investigator or employee of the Investigator or clinical site with direct involvement in this 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 this study, or any employees of Medicago.

Locations (14)

Optimal Sites

Huntsville, Alabama, United States

Synexus

Chandler, Arizona, United States

Optimal Sites

San Diego, California, United States

Optimal Sites

Melbourne, Florida, United States

Global AES

Orlando, Florida, United States

Global AES

The Villages, Florida, United States

Optimal Sites

Peoria, Illinois, United States

Synexus

Evansville, Indiana, United States

Optimal Sites

Rockville, Maryland, United States

Vitalink Research

Anderson, South Carolina, United States

...and 4 more locations

Outcomes

Primary Outcomes

Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous Influenza Strain on Day 0

Time frame: Day 0 (pre-vaccination)

GMTs of HI Antibody Response for Each Homologous Influenza Strain on Day 28

Time frame: Day 28

Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 28

Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable HI titer (i.e. \< 10) pre-vaccination (Day 0) to an HI titer of ≥ 40 on Day 28 was measured using an HI assay for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).

Time frame: Day 0 (pre-vaccination) up to Day 28

Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 28

Time frame: Day 0 (pre-vaccination) up to Day 28

Geometric Mean Fold Rise (GMFR) Measured by HI Antibody Response for Each Homologous Influenza Strain (Day 28/Day 0)

GMFR, the geometric mean of the ratio of GMTs (Day 28/Day 0) in each treatment group was measured using an HI assay for the homologous strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).

Time frame: Day 0 (pre-vaccination), Day 28

Number of Participants With at Least One Immediate Adverse Event (AE)

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling, and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck.

Time frame: Up to 30 minutes post-vaccination

Number of Participants With at Least One Immediate AE of Grade 1, 2, 3, or 4

Time frame: Up to 30 minutes post-vaccination

Number of Participants With at Least One Immediate AE Related to Vaccination

An AE is defined in OM #6. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. A related AE is an event where the investigator determined that the relationship to study vaccine was "Possibly Related", "Probably Related" or "Definitely Related". If a participant reported multiple occurrences of the same AE, only the most closely related occurrence was presented. The causal relationship of all solicited local and systemic AEs was considered related to vaccination. Participants with any related AE was reported.

Time frame: 30 minutes post-vaccination

Number of Participants With at Least One Solicited Local or Systemic AE From Day 0 up to Day 7

Time frame: Day 0 (pre-vaccination) up to Day 7

Number of Participants With at Least One Solicited Local or Systemic AE of Grade 1, 2, 3, or 4 From Day 0 up to Day 7

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. The intensity of the AEs was graded according to the FDA Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4).

Time frame: Day 0 (pre-vaccination) up to Day 7

Number of Participants With at Least One Unsolicited AE From Day 0 up to Day 28

Time frame: Day 0 (pre-vaccination) up to Day 28

Number of Participants With at Least One Unsolicited AE of Grade 1, 2, 3, or 4 From Day 0 up to Day 28

Time frame: Day 0 (pre-vaccination) up to Day 28

Number of Participants With at Least One Unsolicited AE Related to Vaccination From Day 0 up to Day 28

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. A related AE was an event where the Investigator determined that the relationship to study vaccine was "Possibly Related", "Probably Related" or "Definitely Related". If a participant reported multiple occurrences of the same AE, only the most closely related occurrence was presented. Participants with any related AE were reported.

Time frame: Day 0 (pre-vaccination) up to Day 28

Number of Participants With at Least One Serious Adverse Events (SAE) From Day 1 up to Day 28

Time frame: Day 1 up to Day 28

Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 1 up to Day 28

Time frame: Day 1 up to Day 28

Number of Participants With at Least One Adverse Event of Special Interest (AESI) From Day 1 up to Day 28

Time frame: Day 1 up to Day 28

Number of Participants With at Least One Medically Attended AE (MAAE) From Day 1 up to Day 28

Time frame: Day 1 up to Day 28

Number of Participants With at Least One New Onset Clinical Disease (NOCD) From Day 1 up to Day 28

Time frame: Day 1 up to Day 28

Number of Participants With the Occurrence of Death From Day 1 up to Day 28

The number of participants in each treatment group with an occurrence of death was assessed.

Time frame: Day 1 up to Day 28

Number of Participants With at Least One SAE From Day 29 up to Day 182

Time frame: Day 29 up to Day 182

Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 29 up to Day 182

Time frame: Day 29 up to Day 182

Number of Participants With at Least One AESI From Day 29 up to Day 182

Time frame: Day 29 up to Day 182

Number of Participants With at Least One MAAE From Day 29 up to Day 182

Time frame: Day 29 up to Day 182

Number of Participants With at Least One New NOCD From Day 29 up to Day 182

Time frame: Day 29 up to Day 182

Number of Participants With an Occurrence of Death From Day 29 up to Day 182

The number of participants in each treatment group with an occurrence of death was assessed.

Time frame: Day 29 up to Day 182

Number of Participants With at Least One SAE From Day 183 up to Day 365

Time frame: Day 183 up to the end of study (Day 365)

Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 183 up to Day 365

Time frame: Day 183 up to the end of study (Day 365)

Number of Participants With at Least One AESI From Day 183 up to Day 365

Time frame: Day 183 up to the end of study (Day 365)

Number of Participants With at Least One MAAE From Day 183 up to Day 365

Time frame: Day 183 up to the end of study (Day 365)

Number of Participants With at Least One NOCD From Day 183 up to Day 365

All NOCDs that may plausibly have an allergic, autoimmune or inflammatory component were assessed and reported. Plausibility should be interpreted broadly; the only clear exceptions are degenerative conditions such as osteoarthritis, age-related physiologic changes and life-style diseases. In this context, most cancers, cardiac conditions, and kidney diseases should be reported.

Time frame: Day 183 up to the end of study (Day 365)

Number of Participants With an Occurrence of Death From Day 183 up to Day 365

The number of participants in each treatment group with an occurrence of death was assessed.

Time frame: Day 183 up to the end of study (Day 365)

Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 0

Participants were monitored for any abnormal findings in urine parameters (urine color, glucose, occult blood, protein, specific gravity, specimen appearance, pH), hematological parameters (basophils, leukocytes, eosinophils, erythrocytes mean corpuscular hemoglobin, erythrocytes, hematocrit, hemoglobin, lymphocytes, mean platelet volume, monocytes, neutrophils, platelets), and blood chemistry parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, gamma glutamyl transferase, glucose, HDL and LDL cholesterol, phosphate, potassium, protein, sodium, triglycerides, urea nitrogen). Any laboratory result outside of the testing laboratory's normal range was classified as "clinically significant" or "not clinically significant" by the site investigator, with appropriate documentation.

Time frame: Day 0 (pre-vaccination)

Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 3

Time frame: Day 3

Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 28

Participants were monitored for any abnormal findings in urine parameters (urine color, glucose, occult blood, protein, specific gravity, specimen appearance, and pH), hematological parameters (basophils, leukocytes, eosinophils, erythrocytes mean corpuscular hemoglobin, erythrocytes, hematocrit, hemoglobin, lymphocytes, mean platelet volume, monocytes, neutrophils, and platelets), and blood chemistry parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, gamma glutamyl transferase, glucose, cholesterol, phosphate, potassium, protein, sodium, triglycerides, and urea nitrogen). Any laboratory result outside of the testing laboratory's normal range was classified as "clinically significant" or "not clinically significant" by the site investigator, with appropriate documentation.

Time frame: Day 28

Secondary Outcomes

GMTs of HI Antibody Response for Each Homologous Influenza Strain on Day 182 and Day 365

Time frame: Day 182, Day 365

Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 182 and Day 365

Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 182 and Day 0 and Day 365 or a rise of undetectable HI titer (i.e. \<10) pre-vaccination (Day 0) to an HI titer of ≥40 on Day 182 and Day 365 was measured using an HI assay for the following homologous influenza strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).

Time frame: Day 0 (pre-vaccination) up to Day 182 and up to Day 365

Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous Influenza Strain on Day 182 and Day 365

Seroprotection rate: the percentage of participants in a given treatment group attaining a reciprocal HI titer of ≥40 on Day 182 and on Day 365 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination) for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage)

Time frame: Day 0 (pre-vaccination) up to Day 182 and up to Day 365

GMFR Measured by HI Antibody Response for Each Homologous Influenza Strain (Day 182/Day 0 and Day 365/Day 0)

GMFR: the geometric mean of the ratio of GMTs (Day 182/Day 0 and Day 365/Day 0) measured using an HI assay for the homologous strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).

Time frame: Day 0 (pre-vaccination), Day 182, Day 365

Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Heterologous Influenza Strain

Time frame: Day 0 (pre-vaccination) up to Day 28

Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Heterologous Influenza Strain

Time frame: Day 0 (pre-vaccination) up to Day 28

Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Influenza Strain

Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable MN titer (i.e. \<10) pre-vaccination (Day 0) to an MN titer of ≥40 on Day 28 was measured using an MN assay for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage).

Time frame: Day 0 (pre-vaccination) up to Day 28

GMTs of HI Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

The GMTs in each treatment group were measured using an HI assay for the homologous influenza strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination), Day 28

Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable HI titer (i.e. \<10) pre-vaccination (Day 0) to an HI titer of ≥40 on Day 28 was measured using an HI assay for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

Seroprotection rate: the percentage of participants in a given treatment group attaining a reciprocal HI titer of ≥40 on Day 28 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination) for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

GMFR Measured by HI Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0) measured using an HI assay for the homologous strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination), Day 28

GMTs of HI Antibody Response for Each Heterologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

The GMTs in each treatment group were measured using an HI assay for the heterologous influenza strains: A/Brisbane/02/2018 (H1N1), A/Kansas/14/2017 (H3N2), and B/Maryland/15/2016 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination), Day 28

Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Heterologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable HI titer (i.e. \<10) pre-vaccination (Day 0) to an HI titer of ≥40 on Day 28 was measured using an HI assay for the following heterologous influenza strains: A/Brisbane/02/2018 (H1N1), A/Kansas/14/2017 (H3N2), and B/Maryland/15/2016 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Heterologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

Seroprotection rate: the percentage of participants in a given treatment group attaining a reciprocal HI titer of ≥40 on Day 28 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination) for the following heterologous influenza strains: A/Brisbane/02/2018 (H1N1), A/Kansas/14/2017 (H3N2), and B/Maryland/15/2016 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

GMFR Measured by HI Antibody Response for Each Heterologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0) measured using an HI assay for the heterologous strains A/Brisbane/02/2018 (H1N1), A/Kansas/14/2017 (H3N2), and B/Maryland/15/2016 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination), Day 28

GMTs of MN Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

The GMTs in each treatment group were measured using an MN assay for the following homologous influenza strains: A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination), Day 28

Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

Seroconversion rate: the percentage of participants in a given treatment group with either a ≥4-fold increase in reciprocal HI titers between Day 0 and Day 28 or a rise of undetectable MN titer (i.e. \<10) pre-vaccination (Day 0) to an MN titer of ≥40 on Day 28 was measured using an MN assay for the homologous influenza strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

GMFR Measured by MN Antibody Response for Each Homologous Influenza Strain, Stratified by Prior Influenza Vaccination Status

GMFR: the geometric mean of the ratio of GMTs (Day 28/Day 0) measured using an MN assay for the strains A/Hawaii/70/2019 (H1N1), A/Minnesota/41/2019 (H3N2), B/Singapore/INFKK-16-0569/2016 (B/Yamagata lineage), and B/Washington/02/2019 (B/Victoria lineage). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination), Day 28

Number of Participants With at Least One Immediate AE, Stratified by Prior Influenza Vaccination Status

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Up to 30 minutes post-vaccination

Number of Participants With at Least One Immediate AE of Grade 1, 2, 3, or 4, Stratified by Prior Influenza Vaccination Status

An AE is defined in OM #6. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. The intensity of the AEs was graded according to the FDA Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Up to 30 minutes post-vaccination

Number of Participants With at Least One Immediate AE Related to Vaccination, Stratified by Prior Influenza Vaccination Status

An AE is defined in OM #6. Immediate AEs were defined as any solicited (local and systemic) and unsolicited AEs that started up to 30 minutes after vaccination. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. A related AE is an event where the investigator determined that the relationship to study vaccine was "Possibly Related", "Probably Related", or "Definitely Related". If a participant reported multiple occurrences of the same AE, only the most closely related occurrence was presented. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Up to 30 minutes post-vaccination

Number of Participants With at Least One Solicited Local or Systemic AE, Stratified by Prior Influenza Vaccination Status

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 7

Number of Participants With at Least One Solicited Local or Systemic AE of Grade 1, 2, 3, or 4, Stratified by Prior Influenza Vaccination Status

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. Solicited local AEs included erythema, swelling and pain at the injection site. Solicited systemic AEs included fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. The intensity of the AEs was graded according to the FDA Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 7

Number of Participants With at Least One Unsolicited AE, Stratified by Prior Influenza Vaccination Status

Time frame: Day 0 (pre-vaccination) up to Day 28

Number of Participants With at Least One Unsolicited AE of Grade 1, 2, 3, or 4, Stratified by Prior Influenza Vaccination Status

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. The intensity of the AEs was graded according to the FDA Toxicity Grading Scale: mild (Grade 1), moderate (Grade 2), severe (Grade 3), or potentially life threatening (Grade 4). It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

Number of Participants With at Least One Unsolicited AE Related to Vaccination, Stratified by Prior Influenza Vaccination Status

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. A related AE was an event where the Investigator determined that the relationship to study vaccine was "Possibly Related", "Probably Related", or "Definitely Related". It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination) up to Day 28

Number of Participants With at Least One SAE From Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365, Stratified by Prior Influenza Vaccination Status

An AE is defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product, with or without a causal relationship with the treatment. An AE can be any favorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to a medicinal product. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365

Number of Participants With at Least One AE Leading to Withdrawal From the Study From Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365, Stratified by Prior Influenza Vaccination Status

Time frame: Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365

Number of Participants With at Least One AESI From Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365, Stratified by Prior Influenza Vaccination Status

Time frame: Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365

Number of Participants With at Least One MAAE From Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365, Stratified by Prior Influenza Vaccination Status

Time frame: Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365

Number of Participants With at Least One NOCD From Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365, Stratified by Prior Influenza Vaccination Status

All NOCDs that may plausibly have an allergic, autoimmune or inflammatory component were assessed and reported. Plausibility was interpreted broadly; the only clear exceptions were degenerative conditions such as osteoarthritis, age-related physiologic changes and life-style diseases. In this context, most cancers, cardiac conditions, and kidney diseases had to be reported. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365

Number of Participants With the Occurrence of Death From Day 1 up to Day 28, From Day 29 to Day 182, and From Day 183 to Day 365, Stratified by Prior Influenza Vaccination Status

The number of participants in each treatment group with an occurrence of death was assessed. It was planned that the endpoint would be analyzed only if \>25% of the enrolled participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 1 up to Day 28, Day 29 up to Day 182, and Day 183 up to Day 365

Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 0, Stratified by Prior Influenza Vaccination Status

Participants were monitored for abnormal findings in urine parameters (urine color, glucose, occult blood, protein, specific gravity, specimen appearance, pH), hematological parameters (basophils, leukocytes, eosinophils, erythrocytes mean corpuscular hemoglobin, erythrocytes, hematocrit, hemoglobin, lymphocytes, mean platelet volume, monocytes, neutrophils, platelets), and blood chemistry parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, chloride, cholesterol, creatinine, gamma glutamyl transferase, glucose, HDL and LDL cholesterol, phosphate, potassium, protein, sodium, triglycerides, urea nitrogen). Any laboratory result outside of the normal range was classified as "clinically significant" or "not clinically significant" by the site investigator. It was planned that the endpoint would be analyzed if \>25% of the participants had received a standard influenza vaccine during the 12 months prior to study vaccination.

Time frame: Day 0 (pre-vaccination)

Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 3, Stratified by Prior Influenza Vaccination Status

Time frame: Day 3

Number of Participants With Clinically Significant Abnormal Urine, Hematological, and Blood Biochemistry Values on Day 28, Stratified by Prior Influenza Vaccination Status

Time frame: Day 28

Adjuvanted Seasonal Recombinant Quadrivalent Virus-Like Particles (QVLP) Influenza Vaccine in Adults 65 Years of Age and Older

Overview

Conditions

Interventions

Eligibility

Locations (14)

Outcomes

Primary Outcomes

Secondary Outcomes