Virus Diseases, RNA Virus Infections, Respiratory Tract Diseases, Respiratory Tract Infections, Influenza
Conditions
Keywords
Influenza, Human, RNA Virus Infections, Efficacy, Immunologic, Immunogenic Factors, Physiological Effects of Drug, Virus Diseases, Orthomyxoviridae Infections, Infection, Vaccine, Safety, Plant-made, Virus-like Particle, Hemagglutinin, Quadrivalent Influenza Vaccine
Brief summary
This Phase 3 study is intended to assess the efficacy of the Quadrivalent VLP Influenza Vaccine during the 2017-2018 influenza season in healthy adults 18 to 64 years of age. One dose of Quadrivalent VLP Influenza Vaccine (30 μg/strain) or of placebo will be administered to approximately 10,000 participants
Detailed description
This randomized, observer-blind, placebo-controlled multicenter, Phase 3 study will be conducted at multiple sites. The composition of the Quadrivalent VLP Influenza Vaccine to be used in this study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs for the 2017-2018 influenza virus strains. Approximately 10,000 healthy male and female participants aged 18 to 64 years will be randomized in a 1:1 ratio into one of two parallel treatment groups, such that approximately 5,000 participants will receive the Quadrivalent VLP Influenza Vaccine at a dose of 30 μg/strain and approximately 5,000 participants will receive the placebo. Within the two treatment groups, participants will be stratified by site and two age groups (18-49 years of age and 50-64 years of age in a 1:1 ratio). Participants will participate in this study for approximately eight to ten months, during which a first visit will be scheduled on Day 0 for screening and vaccine administration.
Interventions
BIOLOGICALQuadrivalent VLP Vaccine
Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine
BIOLOGICALPlacebo
Single dose of a Placebo
Sponsors
Medicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Observer-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must meet all of the following inclusion criteria to be eligible for participation in this study; no protocol waivers are allowed: 1. Participants must have a body mass index (BMI) below 40 kg/m\^2; 2. Participants are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study; 3. Participants must be in good general health prior to study participation, with no clinically relevant abnormalities that could jeopardize participant safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (thereafter referred as Investigator) and determined by medical history, physical examination, and vital signs; Note: Participants with a pre-existing chronic disease will be allowed to participate if the disease is stable and, according to the Investigator's judgment, the condition is unlikely to confound the results of the study or pose additional risk to the participant by participating in the study. Stable disease is generally defined as no new onset or exacerbation of pre-existing chronic disease three months prior to vaccination. Based on the Investigator's judgment, a participant with more recent stabilization of a disease could also be eligible. 4. Female participants must have a negative urine pregnancy test result at the Screening/Vaccination visit (Visit 1). 5. Female participants of childbearing potential must use an effective method of contraception for one month prior to vaccination and agree to continue employing adequate birth control measures for at least 60 days post-vaccination. Moreover, female participants must have no plan to become pregnant for at least two months post-vaccination. Abstinent participants should be asked what method(s) they would use should their circumstances change, and participants without a well-defined plan should be excluded. The following relationship or methods of contraception are considered to be effective: * Hormonal contraceptives (e.g. oral, injectable, topical \[patch\], or estrogenic vaginal ring); * Intra-uterine device with or without hormonal release; * Male partner using a condom plus spermicide or sterilized partner (at least one year prior to vaccination); * Credible self-reported history of heterosexual vaginal intercourse abstinence until at least 60 days post-vaccination; * Female partner; 6. Non-childbearing females are defined as: * Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to vaccination); or * Post-menopausal (absence of menses for 24 consecutive months and age consistent with natural cessation of ovulation).
Exclusion criteria
Participants who meet any of the following criteria will be excluded from participating in this study; no protocol waivers are allowed: 1. Any participant whose medical condition(s) is sufficiently severe that annual influenza vaccination would be routinely recommended in the jurisdiction of recruitment, as per the Investigator's judgement; 2. According to the Investigator's opinion, history of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. 'Uncontrolled' is defined as: * Requiring a new medical or surgical treatment during the three months prior to study vaccine administration unless the criteria outlined in inclusion criterion no. 5 can be met (i.e. the Investigator can justify inclusion based upon the innocuous nature of medical/surgical events and/or treatments); * Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) during the three months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change meets the criteria outlined in inclusion criterion no. 5 and is appropriately justified by the Investigator. 3. Any medical or neuropsychiatric condition or any history of excessive alcohol use or drug abuse which, in the Investigator's opinion, would render the participant unable to provide informed consent or unable to provide valid safety observations and reporting; 4. Any autoimmune disease other than hypothyroidism on stable replacement therapy (including, but not limited to rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and inflammatory bowel disease) or any confirmed or suspected immunosuppressive condition or immunodeficiency including known or suspected human immunodeficiency virus (HIV), Hepatitis B or C infection, the presence of lymphoproliferative disease; 5. History of chronic pulmonary (including asthma, bronchopulmonary dysplasia, and cystic fibrosis) or cardiovascular (except isolated hypertension), renal, hepatic, neurologic, hematologic (including anemia and hemoglobinopathy), or metabolic disorders (including diabetes mellitus); 6. Because this is a placebo-controlled study, any participants in close contact with individuals considered to be at high risk for developing influenza-related complications (individuals considered at high risk for complications include adults and children who have chronic pulmonary or cardiovascular \[except isolated hypertension\], renal, hepatic, neurologic, hematologic, or metabolic disorders \[including diabetes mellitus\]). 7. Administration or planned administration of any non-influenza vaccine within 30 days prior to randomization up to blood sampling on Day 21. Immunization on an emergency basis will be evaluated case-by-case by the Investigator; 8. Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study; 9. Administration of any 'standard', non-adjuvanted influenza vaccine (e.g. live attenuated trivalent/quadrivalent inactivated influenza vaccine or split trivalent/quadrivalent inactivated influenza vaccine administered by intranasal, intradermal, or intramuscular route) within six months prior to randomization and up to completion of the study; 10. Use of any investigational or non-registered product within 30 days or five half-lives, whichever is longer, prior to randomization or planned use during the study period. Participants may not participate in any other investigational or marketed drug study while participating in this study until after the study; 11. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for 10 or more days in total, within one month of study vaccine administration; any other cytotoxic or immunosuppressant drug, or any immunoglobulin preparation within three months of vaccination and until the completion of the study. Low doses of nasal or inhaled glucocorticoids are allowed. Topical steroids are permitted; 12. Any significant disorder of coagulation including, but not limited to, treatment with warfarin derivatives or heparin. Persons receiving prophylactic anti-platelet medications (e.g. low-dose aspirin \[no more than 325 mg/day\]), and without a clinically apparent bleeding tendency are eligible. Participants treated with new generation drugs that do not increase the risk of intramuscular bleeding (e.g. clopidogrel) are also eligible; 13. History of allergy to any of the constituents of the Quadrivalent VLP Influenza Vaccine or tobacco; 14. History of anaphylactic allergic reactions to plants or plants components; 15. Use of antihistamines with systemic absorption for more than 14 days in the four weeks prior to vaccination or use of antihistamines 48 hours prior to study vaccination (the use of topical antihistamines and nasal or inhaled steroids is acceptable); 16. Use of prophylactic medications (e.g. acetaminophen/paracetamol, aspirin, naproxen, or ibuprofen) within 24 hours of randomization to prevent or pre-empt symptoms due to vaccination. Any participant discovered to have taken a prophylactic medication to prevent or pre-empt symptoms due to vaccination within the 24 hours prior to planned randomization must be delayed until at least the 24 hours period is met; 17. Planned use of influenza antiviral treatment medication before the collection of nasopharyngeal swabs (e.g. oseltamivir, zanamivir, rapivab); 18. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that may interfere with injection site reaction rating; 19. Participants who have received a blood transfusion within 90 days prior to study vaccination; 20. Any female participant who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating; 21. Participants with abnormal vital signs (systolic blood pressure \[BP\] \> 140 mmHg and/or diastolic BP ≥ 90 mmHg, heart rate ≤ 45 beats/min and ≥ 100 beats/min) evaluated by an Investigator to be clinically significant. A participant with abnormal vital signs results may be included in the study based on Investigator's judgment (e.g. a resting hear rate ≤ 45 in highly trained athletes); 22. Presence of any febrile illness (including an oral temperature ≥ 38.0 ˚C within 24 hours prior to vaccination. Such participants may be re-evaluated for enrolment after resolution of illness; 23. Cancer or treatment for cancer within three years prior to study vaccine administration. Persons with a history of cancer who are disease-free without treatment for three years or more are eligible. However, individuals with conditions such as treated and uncomplicated basal cell carcinoma of the skin or non-treated, non-disseminated local prostate cancer may be eligible; 24. Participants identified as an Investigator or employee of the Investigator or clinical site 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 or any employee of Medicago; 25. Participants with a history of Guillain-Barré Syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Occurrences of Protocol-Defined Respiratory Illness Caused by Vaccine-Matched Influenza Strains | Day 14 (post-vaccination) up to ~8 months | Occurrences of protocol-defined respiratory illness caused by vaccine-matched influenza strains were assessed. The vaccine-matched strains included: H1N1 (A/Michigan/45/2015); H3N2 (A/Hong Kong/4801/2014); B/Brisbane (B/Brisbane/60/2008); and B/Phuket (B/Phuket/3073/2013A). The protocol-defined respiratory illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sneezing, stuffy nose, sore throat, cough, sputum production, wheezing, or difficulty breathing. Occurrences of all matched strains are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Occurrences of Laboratory-Confirmed Protocol-Defined Influenza-Like Illness (ILI) Caused by Vaccine-Matched Influenza Strains | Day 14 (post-vaccination) up to ~8 months | Occurrences of protocol-defined ILI due to laboratory-confirmed influenza caused by influenza viral types/subtypes that are matched (and/or antigenically similar) to the strains covered in the vaccine formulation were assessed. A participant is considered to have protocol-defined ILI if the participant met at least one of the following pre-defined respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing AND at least one of the following systemic symptoms: fever (defined as a temperature \> 37.2 °C or \> 99.0 °F), chills, tiredness, headache or myalgia. |
| Number of Occurrences of Laboratory-Confirmed ILI Caused by Any Influenza Strain | Day 14 (post-vaccination) up to ~8 months | Occurrences of laboratory-confirmed ILI caused by any influenza viral strains were assessed. A participant is considered to have protocol-defined ILI if the participant met at least one of the following pre-defined respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing AND at least one of the following systemic symptoms: fever (defined as a temperature \> 37.2 °C or \> 99.0 °F), chills, tiredness, headache or myalgia. |
| Number of Occurrences of Protocol-Defined ILI Cases | Day 14 (post-vaccination) up to ~8 months | Occurrences of protocol-defined ILI cases (confirmed or not) were assessed. A participant is considered to have protocol-defined ILI if the participant met at least one of the following pre-defined respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing AND at least one of the following systemic symptoms: fever (defined as a temperature \> 37.2 °C or \> 99.0 °F), chills, tiredness, headache or myalgia. |
| Number of Participants With at Least One Immediate Complaint | 15 minutes post vaccination | Immediate complaints were defined as any solicited local or systemic reactions. Solicited local reactions included: erythema, swelling, and pain at the injection site and solicited systemic reactions included: fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck. |
| Number of Participants With at Least One Solicited Local and Systemic Reactions | Day 0 (post-vaccination) up to Day 7 | Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck). Any solicited local or systemic immediate complaint was also included. |
| Number of Participants With ≥ Severe Solicited Local and Systemic Reactions | Day 0 (post-vaccination) up to Day 7 | Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck). Any solicited local or systemic immediate complaint was also included. The intensity of the solicited reactions was graded as mild (1)-easily tolerated and does not interfere with usual activity; moderate (2)-interferes with daily activity, but the participant is still able to function; severe (3)-incapacitating and the participant is unable to work or complete usual activity or potentially life threatening; (4)-likely to be life-threatening if not treated in a timely manner, according to the Food and Drug Administration (FDA) Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. |
| Number of Participants With ≥ Severe Related Solicited Reactions | Day 0 (post-vaccination) up to Day 7 | Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (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 solicited reactions was graded according to the FDA Toxicity Grading Scale: mild (1), moderate (2), severe (3) or potentially life threatening (4). The causal relationship with the study vaccine was assessed as definitely not related (clearly not related), probably not related (no medical evidence), possibly related (reasonable possibility of cause and effect), probably related (plausible biologic mechanism and temporal relationship) or definitely related (direct cause and effect relationship). The ≥ severe events included severe and potentially life-threatening and the related category included possibly related, probably related, and definitely related. |
| Number of Participants With Unsolicited Treatment-Emergent Adverse Events (TEAEs) | Day 0 (post-vaccination) up to Day 21 | Participants were monitored for unsolicited TEAEs (e.g., nasopharyngitis, upper respiratory tract infection, headache, and oropharyngeal pain). An adverse event (AE) or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation 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 AE was considered treatment-emergent if it began on or after the date and time of Study Day 0 vaccination. |
| Number of Participants With ≥ Severe Unsolicited TEAEs | Day 0 (post-vaccination) up to Day 21 | The intensity of the unsolicited TEAEs was graded as mild (1)-easily tolerated and does not interfere with usual activity; moderate (2)-interferes with daily activity, but the participant is still able to function; severe (3)-incapacitating and the participant is unable to work or complete usual activity or potentially life threatening; (4)-likely to be life-threatening if not treated in a timely manner, according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. The ≥ Severe events included severe and potentially life-threatening events. AE and TEAEs are defined in outcome measure #10. |
| Number of Participants With ≥ Severe Related Unsolicited Reactions | Day 0 (post-vaccination) up to Day 21 | The intensity of the solicited local and systemic reactions was graded as: mild (1), moderate (2), severe (3) or potentially life threatening (4). The causal relationship with the study vaccine was assessed as definitely not related (clearly not related), probably not related (no medical evidence), possibly related (reasonable possibility of cause and effect), probably related (plausible biologic mechanism and temporal relationship) or definitely related (direct cause and effect relationship). The ≥ severe events included severe and potentially life-threatening and the related category included possibly related, probably related, and definitely related. AE and TEAEs are defined in outcome measure #10. |
| Number of Participants With an Occurrence of Death | Day 0 up to ~8 months | The number of participants in each treatment group with an occurrence of death was assessed. |
| Number of Participants With at Least One Serious TEAE | Day 0 up to ~8 months | A serious adverse event (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. An SAE was considered treatment-emergent if it was aggravated in severity or frequency following the administration of the study vaccine, up to and including the last visit of the study. AE is defined in outcome measure #10. |
| Number of Occurrences of Protocol-Defined Respiratory Illness Cases Caused by Any Laboratory Confirmed Influenza Strain | Day 14 (post-vaccination) up to ~8 months | Occurrences of protocol-defined respiratory illness due to laboratory-confirmed influenza strain (matched, mismatched, and un-typed) were assessed. A protocol-defined respiratory illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sneezing, stuffy nose, sore throat, cough, sputum production, wheezing, or difficulty breathing. |
| Number of Participants With at Least One New Onset Chronic Diseases (NOCDs) | Day 0 up to ~8 months | 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. |
| Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Day 0 (pre-vaccination), Day 21 | The GMTs in each treatment group were measured using a HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004. |
| Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Day 0 (pre-vaccination) up to Day 21 | 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 21 or a rise of undetectable HI titer (i.e. \< 10) pre-vaccination (Day 0) to an HI titer of ≥ 40 on Day 21 was measured using an HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004. |
| Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Day 0 (pre-vaccination) up to Day 21 | Seroprotection rate: the percentage of participants in a given treatment group attaining a reciprocal HI titer of ≥ 40 on Day 21 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination) was measured using an HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004. |
| Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Day 0 (pre-vaccination), Day 21 | GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0) in each treatment group was measured using an HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004. |
| GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination), Day 21 | The GMTs in each treatment group were measured using an MN assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013. |
| Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination) up to Day 21 | Seroconversion rate: the percentage of participants in a given treatment group with either a ≥ 4-fold increase in reciprocal MN titers between Day 0 and Day 21 or a rise of undetectable MN titer (i.e. 7.1) pre-vaccination (Day 0) to an MN titer of ≥ 28.3 at Day 21 post-vaccination were measured using an MN assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013. |
| GMFR of MN Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination), Day 21 | GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0) was measured in each treatment group using an MN assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, and B/Phuket/3073/2013. |
| Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination), Day 21 | The GMA in each treatment group were measured using an SRH assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013. The GMA calculations were performed by taking the anti-log of the mean of the log titer transformations. |
| Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination) up to Day 21 | Seroconversion rate: the percentage of participants in a given treatment group showing at least 50 % increase in GMA between Days 0 and 21 were measured using a SRH assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013. |
| Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination) up to Day 21 | Seroprotection rate: the percentage of participants in a given treatment group attaining an area ≥ 25 mm\^2 following vaccination (Day 21) were measured using an SRH assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013. |
| GMFR of SRH Antibody Response for Each Homologous Strain | Day 0 (pre-vaccination), Day 21 | GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0) was measured in each treatment group using an SRH assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, and B/Phuket/3073/2013. |
| Number of Participants With at Least One AE Leading to Withdrawal | Day 0 up to ~8 months | An AE or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation 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 number of participants with at least one adverse event leading to withdrawal was assessed. |
Countries
Canada, Finland, Germany, Philippines, Thailand, United Kingdom, United States
Participant flow
Recruitment details
Participants were randomized in a 1:1 ratio to receive the Quadrivalent virus-like particle (VLP) Influenza Vaccine at a dose of 30 μg/strain or the placebo.
Pre-assignment details
Participants were healthy adults 18 to 64 years of age assessed during the 2017-2018 influenza season.
Participants by arm
| Arm | Count |
|---|---|
| Quadrivalent VLP Vaccine Participants received one IM injection of 0.5 mL of 30 μg/strain of the Quadrivalent VLP Influenza Vaccine on Day 0. | 5,064 |
| Placebo Participants received one IM injection of 0.5 mL of placebo on Day 0. | 5,072 |
| Total | 10,136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 263 | 282 |
| Overall Study | Miscellaneous | 8 | 4 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Randomized, not vaccinated | 13 | 10 |
| Overall Study | Withdrawal by Subject | 59 | 65 |
Baseline characteristics
| Characteristic | Quadrivalent VLP Vaccine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5064 Participants | 5072 Participants | 10136 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 293 Participants | 326 Participants | 619 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4769 Participants | 4740 Participants | 9509 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 20 Participants | 18 Participants | 38 Participants |
| Race (NIH/OMB) Asian | 1192 Participants | 1185 Participants | 2377 Participants |
| Race (NIH/OMB) Black or African American | 646 Participants | 620 Participants | 1266 Participants |
| Race (NIH/OMB) More than one race | 23 Participants | 23 Participants | 46 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) White | 3168 Participants | 3214 Participants | 6382 Participants |
| Sex: Female, Male Female | 3051 Participants | 3034 Participants | 6085 Participants |
| Sex: Female, Male Male | 2013 Participants | 2038 Participants | 4051 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 5,064 | 2 / 5,072 |
| other Total, other adverse events | 930 / 5,064 | 918 / 5,072 |
| serious Total, serious adverse events | 55 / 5,064 | 51 / 5,072 |
Outcome results
Primary
Number of Occurrences of Protocol-Defined Respiratory Illness Caused by Vaccine-Matched Influenza Strains
Occurrences of protocol-defined respiratory illness caused by vaccine-matched influenza strains were assessed. The vaccine-matched strains included: H1N1 (A/Michigan/45/2015); H3N2 (A/Hong Kong/4801/2014); B/Brisbane (B/Brisbane/60/2008); and B/Phuket (B/Phuket/3073/2013A). The protocol-defined respiratory illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sneezing, stuffy nose, sore throat, cough, sputum production, wheezing, or difficulty breathing. Occurrences of all matched strains are reported.
Time frame: Day 14 (post-vaccination) up to ~8 months
Population: The Per Protocol (PP) set consisted of the participants who participated in the study until at least the end of the peak period or for at least five months or until the end of the surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Occurrences of Protocol-Defined Respiratory Illness Caused by Vaccine-Matched Influenza Strains | 110 Number of cases |
| Placebo | Number of Occurrences of Protocol-Defined Respiratory Illness Caused by Vaccine-Matched Influenza Strains | 169 Number of cases |
95% CI: [17.6, 48.6]
Secondary
Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain
The GMA in each treatment group were measured using an SRH assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013. The GMA calculations were performed by taking the anti-log of the mean of the log titer transformations.
Time frame: Day 0 (pre-vaccination), Day 21
Population: IPP Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 0 | 10.3 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 21 | 31.4 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 0 | 15.6 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 21 | 56.0 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 8.2 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 21 | 31.9 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 11.4 mm^2 |
| Quadrivalent VLP Vaccine | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 36.7 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 15.5 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 0 | 15.4 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 6.8 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 21 | 20.9 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 11.7 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 0 | 19.3 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 21 | 9.3 mm^2 |
| Placebo | Geometric Mean Area (GMA) of Single Radial Hemolysis (SRH) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 21 | 28.4 mm^2 |
Secondary
Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain
GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0) in each treatment group was measured using an HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004.
Time frame: Day 0 (pre-vaccination), Day 21
Population: IPP Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1) | 3.4 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2) | 5.5 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008) | 2.2 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013) | 3.1 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1) | 1.1 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2) | 2.5 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006) | 2.4 Ratio |
| Quadrivalent VLP Vaccine | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004) | 2.2 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004) | 1.0 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1) | 1.0 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1) | 1.0 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2) | 1.0 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006) | 0.9 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008) | 0.9 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2) | 0.9 Ratio |
| Placebo | Geometric Mean Fold Ratio (GMFR) of HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013) | 0.9 Ratio |
Secondary
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain
The GMTs in each treatment group were measured using a HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004.
Time frame: Day 0 (pre-vaccination), Day 21
Population: Immunogenicity Per Protocol (IPP) Set consisted of a subset of participants who participated in the immunogenicity portion of the study, who had a Day 21 immunogenicity sample collection.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (HIN1): Day 0 | 24.2 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (HIN1): Day 21 | 84.8 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (H3N2): Day 0 | 26.2 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (H3N2): Day 21 | 144.9 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Brisbane/60/2008): Day 0 | 12.8 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Brisbane/60/2008): Day 21 | 28.1 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Phuket/3073/2013): Day 0 | 28.8 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Phuket/3073/2013): Day 21 | 87.8 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (HIN1): Day 0 | 14.5 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (HIN1): Day 21 | 16.4 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (H3N2): Day 0 | 17.2 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (H3N2): Day 21 | 44.1 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Florida/4/2006): Day 0 | 26.8 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Florida/4/2006): Day 21 | 65.3 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Malaysia/2506/2004): Day 0 | 11.5 Titers |
| Quadrivalent VLP Vaccine | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Malaysia/2506/2004): Day 21 | 24.6 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Malaysia/2506/2004): Day 21 | 10.6 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (HIN1): Day 0 | 30.0 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (HIN1): Day 0 | 14.5 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (HIN1): Day 21 | 27.8 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Florida/4/2006): Day 0 | 31.5 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (H3N2): Day 0 | 29.0 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (HIN1): Day 21 | 14.4 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (H3N2): Day 21 | 28.0 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Malaysia/2506/2004): Day 0 | 10.7 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Brisbane/60/2008): Day 0 | 12.9 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (H3N2): Day 0 | 19.7 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Brisbane/60/2008): Day 21 | 12.1 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (B/Florida/4/2006): Day 21 | 26.0 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Phuket/3073/2013): Day 0 | 28.1 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Heterologous (H3N2): Day 21 | 17.7 Titers |
| Placebo | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition (HI) Antibody Response for Each Homologous and Heterologous Influenza Strain | Homologous (B/Phuket/3073/2013): Day 21 | 26.4 Titers |
Secondary
GMFR of MN Antibody Response for Each Homologous Strain
GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0) was measured in each treatment group using an MN assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, and B/Phuket/3073/2013.
Time frame: Day 0 (pre-vaccination), Day 21
Population: IPP Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (HIN1) | 4.0 Ratio |
| Quadrivalent VLP Vaccine | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (H3N2) | 2.5 Ratio |
| Quadrivalent VLP Vaccine | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 2.5 Ratio |
| Quadrivalent VLP Vaccine | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 2.8 Ratio |
| Placebo | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 1.1 Ratio |
| Placebo | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (HIN1) | 1.3 Ratio |
| Placebo | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 1.1 Ratio |
| Placebo | GMFR of MN Antibody Response for Each Homologous Strain | Homologous (H3N2) | 1.2 Ratio |
Secondary
GMFR of SRH Antibody Response for Each Homologous Strain
GMFR, the geometric mean of the ratio of GMTs (Day 21/Day 0) was measured in each treatment group using an SRH assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, and B/Phuket/3073/2013.
Time frame: Day 0 (pre-vaccination), Day 21
Population: IPP Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (HIN1) | 2.9 Ratio |
| Quadrivalent VLP Vaccine | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (H3N2) | 3.5 Ratio |
| Quadrivalent VLP Vaccine | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 4.0 Ratio |
| Quadrivalent VLP Vaccine | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 3.2 Ratio |
| Placebo | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 1.3 Ratio |
| Placebo | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (HIN1) | 1.6 Ratio |
| Placebo | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 1.3 Ratio |
| Placebo | GMFR of SRH Antibody Response for Each Homologous Strain | Homologous (H3N2) | 1.6 Ratio |
Secondary
GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain
The GMTs in each treatment group were measured using an MN assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013.
Time frame: Day 0 (pre-vaccination), Day 21
Population: IPP Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 0 | 88.1 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 21 | 366.1 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 0 | 46.7 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 21 | 120.3 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 21 | 38.2 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 18.2 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 52.0 Titers |
| Quadrivalent VLP Vaccine | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 15.2 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 14.9 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 0 | 112.3 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 18.9 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 21 | 135.7 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 21 | 16.0 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 0 | 62.1 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 21.3 Titers |
| Placebo | GMTs of Microneutralization (MN) Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 21 | 67.2 Titers |
Secondary
Number of Occurrences of Laboratory-Confirmed ILI Caused by Any Influenza Strain
Occurrences of laboratory-confirmed ILI caused by any influenza viral strains were assessed. A participant is considered to have protocol-defined ILI if the participant met at least one of the following pre-defined respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing AND at least one of the following systemic symptoms: fever (defined as a temperature \> 37.2 °C or \> 99.0 °F), chills, tiredness, headache or myalgia.
Time frame: Day 14 (post-vaccination) up to ~8 months
Population: PP Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Occurrences of Laboratory-Confirmed ILI Caused by Any Influenza Strain | 178 Number of cases |
| Placebo | Number of Occurrences of Laboratory-Confirmed ILI Caused by Any Influenza Strain | 285 Number of cases |
95% CI: [25.1, 48]
Secondary
Number of Occurrences of Laboratory-Confirmed Protocol-Defined Influenza-Like Illness (ILI) Caused by Vaccine-Matched Influenza Strains
Occurrences of protocol-defined ILI due to laboratory-confirmed influenza caused by influenza viral types/subtypes that are matched (and/or antigenically similar) to the strains covered in the vaccine formulation were assessed. A participant is considered to have protocol-defined ILI if the participant met at least one of the following pre-defined respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing AND at least one of the following systemic symptoms: fever (defined as a temperature \> 37.2 °C or \> 99.0 °F), chills, tiredness, headache or myalgia.
Time frame: Day 14 (post-vaccination) up to ~8 months
Population: PP Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Occurrences of Laboratory-Confirmed Protocol-Defined Influenza-Like Illness (ILI) Caused by Vaccine-Matched Influenza Strains | 98 Number of cases |
| Placebo | Number of Occurrences of Laboratory-Confirmed Protocol-Defined Influenza-Like Illness (ILI) Caused by Vaccine-Matched Influenza Strains | 148 Number of cases |
95% CI: [14.9, 48.5]
Secondary
Number of Occurrences of Protocol-Defined ILI Cases
Occurrences of protocol-defined ILI cases (confirmed or not) were assessed. A participant is considered to have protocol-defined ILI if the participant met at least one of the following pre-defined respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing AND at least one of the following systemic symptoms: fever (defined as a temperature \> 37.2 °C or \> 99.0 °F), chills, tiredness, headache or myalgia.
Time frame: Day 14 (post-vaccination) up to ~8 months
Population: PP Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Occurrences of Protocol-Defined ILI Cases | 1576 Number of cases |
| Placebo | Number of Occurrences of Protocol-Defined ILI Cases | 1679 Number of cases |
95% CI: [0.8, 11.3]
Secondary
Number of Occurrences of Protocol-Defined Respiratory Illness Cases Caused by Any Laboratory Confirmed Influenza Strain
Occurrences of protocol-defined respiratory illness due to laboratory-confirmed influenza strain (matched, mismatched, and un-typed) were assessed. A protocol-defined respiratory illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sneezing, stuffy nose, sore throat, cough, sputum production, wheezing, or difficulty breathing.
Time frame: Day 14 (post-vaccination) up to ~8 months
Population: PP Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Occurrences of Protocol-Defined Respiratory Illness Cases Caused by Any Laboratory Confirmed Influenza Strain | 213 Number of cases |
| Placebo | Number of Occurrences of Protocol-Defined Respiratory Illness Cases Caused by Any Laboratory Confirmed Influenza Strain | 347 Number of cases |
95% CI: [27.6, 48]
Secondary
Number of Participants With an Occurrence of Death
The number of participants in each treatment group with an occurrence of death was assessed.
Time frame: Day 0 up to ~8 months
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With an Occurrence of Death | 1 Participants |
| Placebo | Number of Participants With an Occurrence of Death | 2 Participants |
Secondary
Number of Participants With at Least One AE Leading to Withdrawal
An AE or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation 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 number of participants with at least one adverse event leading to withdrawal was assessed.
Time frame: Day 0 up to ~8 months
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With at Least One AE Leading to Withdrawal | 0 Participants |
| Placebo | Number of Participants With at Least One AE Leading to Withdrawal | 5 Participants |
Secondary
Number of Participants With at Least One Immediate Complaint
Immediate complaints were defined as any solicited local or systemic reactions. Solicited local reactions included: erythema, swelling, and pain at the injection site and solicited systemic reactions 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: 15 minutes post vaccination
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With at Least One Immediate Complaint | 441 Participants |
| Placebo | Number of Participants With at Least One Immediate Complaint | 377 Participants |
Secondary
Number of Participants With at Least One New Onset Chronic Diseases (NOCDs)
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 0 up to ~8 months
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With at Least One New Onset Chronic Diseases (NOCDs) | 54 Participants |
| Placebo | Number of Participants With at Least One New Onset Chronic Diseases (NOCDs) | 41 Participants |
Secondary
Number of Participants With at Least One Serious TEAE
A serious adverse event (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. An SAE was considered treatment-emergent if it was aggravated in severity or frequency following the administration of the study vaccine, up to and including the last visit of the study. AE is defined in outcome measure #10.
Time frame: Day 0 up to ~8 months
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With at Least One Serious TEAE | 55 Participants |
| Placebo | Number of Participants With at Least One Serious TEAE | 51 Participants |
Secondary
Number of Participants With at Least One Solicited Local and Systemic Reactions
Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck). Any solicited local or systemic immediate complaint was also included.
Time frame: Day 0 (post-vaccination) up to Day 7
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With at Least One Solicited Local and Systemic Reactions | 2776 Participants |
| Placebo | Number of Participants With at Least One Solicited Local and Systemic Reactions | 1723 Participants |
Secondary
Number of Participants With ≥ Severe Related Solicited Reactions
Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (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 solicited reactions was graded according to the FDA Toxicity Grading Scale: mild (1), moderate (2), severe (3) or potentially life threatening (4). The causal relationship with the study vaccine was assessed as definitely not related (clearly not related), probably not related (no medical evidence), possibly related (reasonable possibility of cause and effect), probably related (plausible biologic mechanism and temporal relationship) or definitely related (direct cause and effect relationship). The ≥ severe events included severe and potentially life-threatening and the related category included possibly related, probably related, and definitely related.
Time frame: Day 0 (post-vaccination) up to Day 7
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With ≥ Severe Related Solicited Reactions | 56 Participants |
| Placebo | Number of Participants With ≥ Severe Related Solicited Reactions | 62 Participants |
Secondary
Number of Participants With ≥ Severe Related Unsolicited Reactions
The intensity of the solicited local and systemic reactions was graded as: mild (1), moderate (2), severe (3) or potentially life threatening (4). The causal relationship with the study vaccine was assessed as definitely not related (clearly not related), probably not related (no medical evidence), possibly related (reasonable possibility of cause and effect), probably related (plausible biologic mechanism and temporal relationship) or definitely related (direct cause and effect relationship). The ≥ severe events included severe and potentially life-threatening and the related category included possibly related, probably related, and definitely related. AE and TEAEs are defined in outcome measure #10.
Time frame: Day 0 (post-vaccination) up to Day 21
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With ≥ Severe Related Unsolicited Reactions | 4 Participants |
| Placebo | Number of Participants With ≥ Severe Related Unsolicited Reactions | 6 Participants |
Secondary
Number of Participants With ≥ Severe Solicited Local and Systemic Reactions
Participants were monitored for both solicited local reactions (erythema, swelling, and pain at the injection site) and solicited systemic reactions (fever, headache, fatigue, muscle aches, joint aches, chills, a feeling of general discomfort, swelling in the axilla, and swelling in the neck). Any solicited local or systemic immediate complaint was also included. The intensity of the solicited reactions was graded as mild (1)-easily tolerated and does not interfere with usual activity; moderate (2)-interferes with daily activity, but the participant is still able to function; severe (3)-incapacitating and the participant is unable to work or complete usual activity or potentially life threatening; (4)-likely to be life-threatening if not treated in a timely manner, according to the Food and Drug Administration (FDA) Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.
Time frame: Day 0 (post-vaccination) up to Day 7
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With ≥ Severe Solicited Local and Systemic Reactions | 75 Participants |
| Placebo | Number of Participants With ≥ Severe Solicited Local and Systemic Reactions | 85 Participants |
Secondary
Number of Participants With ≥ Severe Unsolicited TEAEs
The intensity of the unsolicited TEAEs was graded as mild (1)-easily tolerated and does not interfere with usual activity; moderate (2)-interferes with daily activity, but the participant is still able to function; severe (3)-incapacitating and the participant is unable to work or complete usual activity or potentially life threatening; (4)-likely to be life-threatening if not treated in a timely manner, according to the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. The ≥ Severe events included severe and potentially life-threatening events. AE and TEAEs are defined in outcome measure #10.
Time frame: Day 0 (post-vaccination) up to Day 21
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With ≥ Severe Unsolicited TEAEs | 13 Participants |
| Placebo | Number of Participants With ≥ Severe Unsolicited TEAEs | 25 Participants |
Secondary
Number of Participants With Unsolicited Treatment-Emergent Adverse Events (TEAEs)
Participants were monitored for unsolicited TEAEs (e.g., nasopharyngitis, upper respiratory tract infection, headache, and oropharyngeal pain). An adverse event (AE) or adverse experience was defined as any untoward medical occurrence in a participant or clinical investigation 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 AE was considered treatment-emergent if it began on or after the date and time of Study Day 0 vaccination.
Time frame: Day 0 (post-vaccination) up to Day 21
Population: SAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent VLP Vaccine | Number of Participants With Unsolicited Treatment-Emergent Adverse Events (TEAEs) | 661 Participants |
| Placebo | Number of Participants With Unsolicited Treatment-Emergent Adverse Events (TEAEs) | 639 Participants |
Secondary
Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous 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 21 or a rise of undetectable HI titer (i.e. \< 10) pre-vaccination (Day 0) to an HI titer of ≥ 40 on Day 21 was measured using an HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004.
Time frame: Day 0 (pre-vaccination) up to Day 21
Population: IPP Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1) | 37.1 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2) | 46.4 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008) | 17.6 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013) | 31.7 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1) | 2.5 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2) | 23.0 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006) | 27.0 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004) | 18.3 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain
Seroconversion rate: the percentage of participants in a given treatment group with either a ≥ 4-fold increase in reciprocal MN titers between Day 0 and Day 21 or a rise of undetectable MN titer (i.e. 7.1) pre-vaccination (Day 0) to an MN titer of ≥ 28.3 at Day 21 post-vaccination were measured using an MN assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013.
Time frame: Day 0 (pre-vaccination) up to Day 21
Population: IPP Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (HIN1) | 41.7 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (H3N2) | 28.1 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 30.6 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 31.3 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 1.0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (HIN1) | 2.1 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by MN Antibody Response for Each Homologous Strain | Homologous (H3N2) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain
Seroconversion rate: the percentage of participants in a given treatment group showing at least 50 % increase in GMA between Days 0 and 21 were measured using a SRH assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013.
Time frame: Day 0 (pre-vaccination) up to Day 21
Population: IPP Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (HIN1) | 53.6 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (H3N2) | 48.2 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 45.7 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 47.1 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013) | 12.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (HIN1) | 14.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008) | 9.3 Percentage of Participants |
| Placebo | Percentage of Participants With Seroconversion Measured by SRH Antibody Response for Each Homologous Strain | Homologous (H3N2) | 14.4 Percentage of Participants |
Secondary
Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain
Seroprotection rate: the percentage of participants in a given treatment group attaining a reciprocal HI titer of ≥ 40 on Day 21 (the percentage of vaccine recipients with a serum HI titer of at least 1:40 following vaccination) was measured using an HI assay for the homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013, and the heterologous strains: A/Brisbane/59/2007 (IVR-148) (HIN1), A/Uruguay/716/2007 (H3N2), B/Florida/4/2006, B/Malaysia/2506/2004.
Time frame: Day 0 (pre-vaccination) up to Day 21
Population: IPP Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1): Day 0 | 40.6 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1): Day 21 | 74.8 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2): Day 0 | 46.4 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2): Day 21 | 85.3 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 19.4 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008: Day 21 | 41.0 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 47.5 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 76.3 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1): Day 0 | 23.4 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1): Day 21 | 27.0 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2): Day 0 | 31.3 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2): Day 21 | 58.6 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006): Day 0 | 46.8 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006): Day 21 | 70.9 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004): Day 0 | 20.1 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004): Day 21 | 43.2 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004): Day 21 | 13.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1): Day 0 | 47.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1): Day 0 | 16.5 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (HIN1): Day 21 | 39.2 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006): Day 0 | 48.5 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2): Day 0 | 46.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (HIN1): Day 21 | 16.5 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (H3N2): Day 21 | 48.5 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Malaysia/2506/2004): Day 0 | 15.5 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 20.6 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2): Day 0 | 34.0 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Brisbane/60/2008: Day 21 | 15.5 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (B/Florida/4/2006): Day 21 | 46.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 46.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Heterologous (H3N2): Day 21 | 29.9 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by HI Antibody Response for Each Homologous and Heterologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 43.3 Percentage of Participants |
Secondary
Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain
Seroprotection rate: the percentage of participants in a given treatment group attaining an area ≥ 25 mm\^2 following vaccination (Day 21) were measured using an SRH assay for homologous strains: H1 A/Michigan/45/2015 (H1N1), A/Hong Kong/4801/2014 (H3N2), B/Brisbane/60/2008, B/Phuket/3073/2013.
Time frame: Day 0 (pre-vaccination) up to Day 21
Population: IPP Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 0 | 36.3 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 21 | 75.9 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 0 | 54.7 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 21 | 92.1 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 40.3 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 21 | 81.3 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 47.5 Percentage of Participants |
| Quadrivalent VLP Vaccine | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 81.7 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 21 | 54.6 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 0 | 42.3 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 0 | 37.1 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (HIN1): Day 21 | 57.7 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Phuket/3073/2013): Day 0 | 44.3 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 0 | 57.7 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (B/Brisbane/60/2008): Day 21 | 45.4 Percentage of Participants |
| Placebo | Percentage of Participants With Seroprotection Measured by SRH Antibody Response for Each Homologous Strain | Homologous (H3N2): Day 21 | 74.2 Percentage of Participants |