Influenza
Conditions
Brief summary
A Phase 2b Study to Determine the Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults aged 18 years and over. To assess the effect of MVA-NP+M1 on the reduction of laboratory confirmed influenza when given as an adjunct to licensed quadrivalent influenza vaccine (QIV) in adults
Detailed description
This is a Phase 2b, multicentre, randomised, single-blind study in up to 6000 adults to compare the efficacy, safety and immunogenicity of MVA-NP+M1 when given as an adjunct to a standard, licensed adult dose of QIV. The study will be conducted on an outpatient basis and will run over two consecutive influenza seasons. It is aimed to recruit 2200 participants in Season 1 and 2800-3800 participants in Season 2.
Interventions
BIOLOGICALMVA-NP+M1
Trial Vaccine
DRUGSaline
Sodium Chloride Placebo
Sponsors
Clinical Network Services (CNS) Pty Ltd
Barinthus Biotherapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female adults aged 18 years and over * Receipt of a standard-dose licensed influenza QIV vaccine on the day of, or within 28 days prior to, randomisation * A female participant is eligible for this study if she is not pregnant or breast feeding and one of the following: 1. Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year) 2. Of childbearing potential but agrees to practice effective contraception 8 weeks post-vaccination and has a negative urine pregnancy test pre-vaccination. Acceptable methods of contraception include one or more of the following: i. Male partner who is sterile prior to the female participant's entry into the study and is the sole sexual partner for the female participant ii. Implants of levonorgestrel iii. Injectable progestogen iv. An intrauterine device with a documented failure rate of \<1% v. Oral contraceptives vi. Double barrier methods including diaphragm or condom vii. Abstinence as long as it is line with the usual and preferred lifestyle of the participant * Participant is willing and has capacity to provide written informed consent for participation in the study (in the Investigator's opinion) * Able and willing (in the Investigator's opinion) to comply with all study requirements * Willing to allow the Investigators to discuss the participant's medical history with their healthcare provider * Present and able to visit the clinic in the event of an ILI episode during the influenza season
Exclusion criteria
* Any other significant disease, disorder or finding (including blood test results), which, in the opinion of the Investigator, would either put the participant at risk because of participation in the study, or may influence the result of the study * Receipt of any investigational product within 6 months prior to study, or prior participation in a clinical study of any Influenza vaccine and agreement not to participate in another clinical study for the duration of study follow-up * Prior receipt of an investigational vaccine likely to impact on interpretation of the study data * Active infection with HIV, Hepatitis B or Hepatitis C (from patient history or medical records) * History of severe allergic reactions (e.g. anaphylaxis) * History of auto-immune disease e.g. Guillain-Barré syndrome * Not willing to comply with study procedures * Immunosuppressed or taking immunosuppressive medications * Use of warfarin or other blood thinning medications (aspirin is acceptable) * Tattoos or birthmarks at the vaccination site * Participant bruises easily, has haematoma or keloid scarring * Receipt of a licenced inactivated vaccine (e.g. pneumococcal vaccine) within 2 weeks prior to vaccination * Receipt of an off licensed live vaccine (e.g. herpes zoster vaccine) within 4 weeks prior to vaccination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) in line with official Australian influenza season. | The measure used reverse transcription polymerase chain reaction (RT-PCR) on deep nasal/mid-turbinate swab samples to record confirmed cases of influenza. If influenza symptoms are experienced at any time during the Follow Up period, after the vaccination, participants will attend the clinic on two occasions, the first as soon as possible and at least within 72 hours of the onset of symptoms for deep nasal swabs to be taken. Both swabs must be taken within 96 hours of symptom onset. The incidence rate of laboratory confirmed influenza using RT-PCR will be estimated for each vaccine group. The 95% CI for the incidence rate will be estimated by mid-p exact method. The difference in incidence rate between vaccine groups will be compared by Fisher's exact method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | 7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October) | The solicited adverse events are commonly observed soon after receipt of vaccines and relate to local and systemic signs and symptoms. The solicited local injection site reactions (ISR) include pain, induration, warmth, and erythema (redness). The solicited systemic reactions include feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, and malaise. Participants completed eDiaries post vaccination to record ISR and systemic reactogenicity over the first 7 days post-vaccination (and the ongoing (S)AEs throughout the study). The participant reporting of all ISR categories and solicited systemic reactions was compared between the MVA-NP+M1 treated group and the Placebo treated group. Diary reported ISRs and solicited systemic reactions were summarized, by vaccination group, using descriptive statistics. |
| Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) | Day 28 and Week 26 | The numbers of Immunogenic Participants (participants with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were summarized and listed. The immunogenicity here was assessed as the geometric mean titers of influenza-specific neutralizing antibodies at different timepoints in relation to the baseline, against the antigens included in the licensed QIV(Influenza A/H3N2 (HI), Influenza A/H3N2 (MN), Influenza A/H3N2 (H1N1pdm), Influenza B/Victoria, and Influenza B/Yamagata). The neutralizing antibody assays included microneutralisation and hemagglutination inhibition titers using standard methodologies for the four strains that were in the licensed vaccine. The immunogenicity analyses were conducted only on the Immunology Analysis Set of Participants. |
| Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) | ILI is defined as feeling feverish or having a fever (feeling feverish or having a fever (≥37.8Celsius)) and at least one of the following symptoms: cough, sore throat. The incidence rate of ILI by the participant completing of eDiaries will be estimated for each vaccine group. The 95% CI for the incidence will be estimated by mid-p exact method. The difference in incidence between groups will be compared by Fisher's exact method. |
| Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) | The severity of ILI was assessed by each participant completing of electronic Diaries for symptom severity daily for the following symptoms: Feeling hot, Temperature, Cough, Sore throat, Blocked nose, Chest pain, Muscle aches, Shortness of breath with their severities (scores) recorded as: Not Present (0), Mild (1), Moderate (2), Severe (3). For each symptom, the severity score was used to calculate the area under the curve (AUC), along with the calendar day, for the entire influenza season using trapezoidal rule. Participants could be followed for varying days in the influenza season, therefore the AUC will be time weighted to 168 days: Time weighted AUC=((raw AUC \[time in days\])/(number of days used for analysis)) \* 168 |
| Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) | Day 28 and Week 26 | The numbers of immunogenic Participants (with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were listed. The immunogenicity here was determined via the frequency of influenza-specific T-cells measured by IFN-γ/granzyme B ELISpot assay (enzyme linked immunospot) where the adjusted Spot Forming Units (SFU) per million PBMCs (peripheral blood mononuclear cells) after background subtraction (dimethyl sulfoxide, DMSO) were counted. The immunogenicity analyses were conducted only in the Immunology Analysis Set of Participants. |
| Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) | The duration of ILI is defined as the duration (days) from the first day ILI criteria met (as defined at the Secondary Outcome Measure 2) until the first day afterwards ILI criteria not met (event, ILI recovery). ILI positive participants with ILI criteria met throughout the entire influenza season were censored at the last day recorded with the ILI dairy. Survival analysis was used for the analysis of duration of ILI. The survival function for the duration of ILI was estimated by the Kaplan-Meier method. |
Countries
Australia
Participant flow
Recruitment details
The single-blind study was conducted at 9 sites across Australia, over one Influenza season.
Pre-assignment details
2364 were screened and 2152 participants started randomized in a 1:1 ratio and received (along with a licensed adult dose of QIV), either active drug (MVA-NP+M1) or Placebo, via IM injection. Overall, 1077 participants received active drug and 1075 Placebo. A total of 2109 participants completed the study. The Immunogenicity Cohort was a subset of 50 participants: 25 participants were administered active drug and 25 participants were administered Placebo. All 50 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| MVA-NP+M1 Group Vaccination administered: 1 dose of MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10\^8 pfu per dose) MVA-NP+M1: Trial Vaccine Vaccinations were administered by intramuscular injection on Day 0. The participants were provided with an oral thermometer, tape measure and electronic diary card (eDiary) and instructed how to complete the eDiary at home.
Participants recorded their oral temperature and any solicited adverse events for 7 days post-vaccination and unsolicited adverse events for 28 days post-vaccination.
The study team contacted participants by telephone on Day 1 (+2 days) post-vaccination and Day 7 (+3 days) post-vaccination for safety follow-up. If the participant had persistent, vaccine-related Grade 3 AEs during the first 4 weeks post-vaccination they could be asked to attend a further clinical assessment.
The Immunogenicity Cohort of the MVA-NP+M1 group (25 participants), had pre vaccination safety laboratory and immunogenicity blood samples taken.
In addition to the visits and procedures outlined above these participants attended an additional three clinic visits on Days 7 (+3 days), 28 (±7 days) and Week 26 (±1 week) (approximate end of the influenza season).
At the end of the influenza season, all participants were contacted by telephone to inform them of the end of the follow-up period and confirm all information had been collected. | 1,077 |
| Saline Placebo Group Vaccination administered: 1 dose of Sodium Chloride (IM injection, 0.5 ml, 0.9% per dose) Saline: Sodium Chloride Placebo Vaccinations were administered by intramuscular injection on Day 0. The participants were provided with an oral thermometer, tape measure and electronic diary card (eDiary) and instructed how to complete the eDiary at home.
Participants recorded their oral temperature and any solicited adverse events for 7 days post-vaccination and unsolicited adverse events for 28 days post-vaccination.
The study team contacted participants by telephone on Day 1 (+2 days) post-vaccination and Day 7 (+3 days) post-vaccination for safety follow-up. If the participant had persistent, vaccine-related Grade 3 AEs during the first 4 weeks post-vaccination they could be asked to attend a further clinical assessment.
The Immunogenicity Cohort of the Placebo group (25 participants), had pre vaccination safety laboratory and immunogenicity blood samples taken.
In addition to the visits and procedures outlined above these participants attended an additional three clinic visits on Days 7 (+3 days), 28 (±7 days) and Week 26 (±1 week) (approximate end of the influenza season).
At the end of the influenza season, all participants were contacted by telephone to inform them of the end of the follow-up period and confirm all information had been collected. | 1,075 |
| Total | 2,152 |
Baseline characteristics
| Characteristic | MVA-NP+M1 Group | Total | Saline Placebo Group |
|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 18.93 | 43.7 years STANDARD_DEVIATION 18.66 | 43.8 years STANDARD_DEVIATION 18.4 |
| Body Mass Index (BMI) | 28.36 kg/m^2 STANDARD_DEVIATION 6.727 | 28.31 kg/m^2 STANDARD_DEVIATION 6.435 | 28.26 kg/m^2 STANDARD_DEVIATION 6.143 |
| Body Temperature | 36.44 degree Celsius STANDARD_DEVIATION 0.42 | 36.44 degree Celsius STANDARD_DEVIATION 0.41 | 36.44 degree Celsius STANDARD_DEVIATION 0.401 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 21 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1061 Participants | 2113 Participants | 1052 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 18 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 143 Participants | 261 Participants | 118 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 16 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 8 Participants | 21 Participants | 13 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 29 Participants | 71 Participants | 42 Participants |
| Race (NIH/OMB) White | 882 Participants | 1774 Participants | 892 Participants |
| Sex/Gender, Customized Female | 631 Participants | 1262 Participants | 631 Participants |
| Sex/Gender, Customized Male | 445 Participants | 888 Participants | 443 Participants |
| Sex/Gender, Customized Unknown | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,077 | 1 / 1,075 |
| other Total, other adverse events | 524 / 1,077 | 435 / 1,075 |
| serious Total, serious adverse events | 18 / 1,077 | 22 / 1,075 |
Outcome results
Primary
Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
The measure used reverse transcription polymerase chain reaction (RT-PCR) on deep nasal/mid-turbinate swab samples to record confirmed cases of influenza. If influenza symptoms are experienced at any time during the Follow Up period, after the vaccination, participants will attend the clinic on two occasions, the first as soon as possible and at least within 72 hours of the onset of symptoms for deep nasal swabs to be taken. Both swabs must be taken within 96 hours of symptom onset. The incidence rate of laboratory confirmed influenza using RT-PCR will be estimated for each vaccine group. The 95% CI for the incidence rate will be estimated by mid-p exact method. The difference in incidence rate between vaccine groups will be compared by Fisher's exact method.
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) in line with official Australian influenza season.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 Group | Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). | Participants with laboratory confirmed influenza using RT-PCR | 35 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). | Participants without laboratory confirmed influenza using RT-PCR | 1042 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). | Participants with laboratory confirmed influenza using RT-PCR | 23 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). | Participants without laboratory confirmed influenza using RT-PCR | 1052 Participants |
p-value: 0.114695% CI: [0.9, 2.55]Log Binominal Model
p-value: 0.114695% CI: [0.9, 2.55]Poisson Model with Robust Variance
Secondary
Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
The duration of ILI is defined as the duration (days) from the first day ILI criteria met (as defined at the Secondary Outcome Measure 2) until the first day afterwards ILI criteria not met (event, ILI recovery). ILI positive participants with ILI criteria met throughout the entire influenza season were censored at the last day recorded with the ILI dairy. Survival analysis was used for the analysis of duration of ILI. The survival function for the duration of ILI was estimated by the Kaplan-Meier method.
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
Population: ILI duration analysis is only applicable for ILI positive participants. In the MVA-NP+M1 Group there were 273 ILI positive participants assessed: 247 with event and 26 censored; In the Placebo Group there were 273 ILI positive participants assessed: 248 with event and 25 censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVA-NP+M1 Group | Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | 3 days |
| Saline Placebo Group | Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | 3 days |
p-value: 0.415995% CI: [0.9, 1.28]Regression, Cox
Secondary
Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
ILI is defined as feeling feverish or having a fever (feeling feverish or having a fever (≥37.8Celsius)) and at least one of the following symptoms: cough, sore throat. The incidence rate of ILI by the participant completing of eDiaries will be estimated for each vaccine group. The 95% CI for the incidence will be estimated by mid-p exact method. The difference in incidence between groups will be compared by Fisher's exact method.
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 Group | Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | Positive ILI Cases | 273 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | Negative ILI Cases | 804 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | Positive ILI Cases | 273 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary | Negative ILI Cases | 802 Participants |
Comparison: The Analysis concerns the Incidence of Influenza-like Illness (ILI)p-value: 195% CI: [0.86, 1.15]Log Binomial Model
Comparison: The Analysis concerns the Incidence of Influenza-like Illness (ILI)p-value: 0.979995% CI: [0.86, 1.15]Poisson Model with Robust Variance
Secondary
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs)
The solicited adverse events are commonly observed soon after receipt of vaccines and relate to local and systemic signs and symptoms. The solicited local injection site reactions (ISR) include pain, induration, warmth, and erythema (redness). The solicited systemic reactions include feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, and malaise. Participants completed eDiaries post vaccination to record ISR and systemic reactogenicity over the first 7 days post-vaccination (and the ongoing (S)AEs throughout the study). The participant reporting of all ISR categories and solicited systemic reactions was compared between the MVA-NP+M1 treated group and the Placebo treated group. Diary reported ISRs and solicited systemic reactions were summarized, by vaccination group, using descriptive statistics.
Time frame: 7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Pain | 292 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Induration | 113 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Warmth | 205 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Erythema | 198 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Severe, Solicited Local Injection Site Reaction | 12 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Chills | 61 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Myalgia | 256 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Fatigue | 248 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Headache | 238 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Nausea | 88 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Arthralgia | 156 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Malaise | 273 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Feverishness | 214 Participants |
| MVA-NP+M1 Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Severe, Solicited Systemic Reaction | 45 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Arthralgia | 57 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Pain | 19 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Fatigue | 117 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Induration | 4 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Feverishness | 93 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Warmth | 18 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Headache | 106 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Local Injection Site Reaction (IRS) - Erythema | 15 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Malaise | 139 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Severe, Solicited Local Injection Site Reaction | 1 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Nausea | 31 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Chills | 18 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Severe, Solicited Systemic Reaction | 14 Participants |
| Saline Placebo Group | Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) | Participants with Solicited Systemic Reactions - Myalgia | 85 Participants |
Secondary
Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies)
The numbers of Immunogenic Participants (participants with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were summarized and listed. The immunogenicity here was assessed as the geometric mean titers of influenza-specific neutralizing antibodies at different timepoints in relation to the baseline, against the antigens included in the licensed QIV(Influenza A/H3N2 (HI), Influenza A/H3N2 (MN), Influenza A/H3N2 (H1N1pdm), Influenza B/Victoria, and Influenza B/Yamagata). The neutralizing antibody assays included microneutralisation and hemagglutination inhibition titers using standard methodologies for the four strains that were in the licensed vaccine. The immunogenicity analyses were conducted only on the Immunology Analysis Set of Participants.
Time frame: Day 28 and Week 26
Population: The samples for immunogenicity analysis were taken only from participants in the 2 Immunogenicity cohorts included in the MVA-NP+M1 Group vs the Placebo Group.~The immunogenicity analysis for Day 28 used a number of 24 participant results from the MVA-NP+M1 Cohort and a number of 24 participant results from the Placebo Cohort.~The immunogenicity analysis for Week26 used a number of 23 participant results from the MVA-NP+M1 Cohort and a number of 25 participant results from the Placebo Cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 Group | Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) | Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Day 28 | 23 Participants |
| MVA-NP+M1 Group | Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) | Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Week 26 | 23 Participants |
| Saline Placebo Group | Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) | Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Day 28 | 24 Participants |
| Saline Placebo Group | Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) | Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Week 26 | 25 Participants |
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza A/H3N2 (MN) at Week 26p-value: 0.750995% CI: [-611.67, 444.32]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza A/H3N2 (HI) at Day 28p-value: 0.328495% CI: [-872.75, 298.59]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza A/H3N2 (HI) at Week26p-value: 0.846895% CI: [-152.26, 125.47]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza A/H3N2 (MN) at Day 28p-value: 0.508795% CI: [-1875.21, 943.75]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza A/H1N1pdm at Day 28p-value: 0.339895% CI: [-250.72, 88.39]ANOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza A/H1N1pdm at Week 26p-value: 0.415495% CI: [-37.95, 90.26]ANCOVA
Comparison: Titers of neutralizing antibodies against Influenza B/ Victoria at Day 28p-value: 0.719395% CI: [-104.5, 150.18]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza B/ Victoria at Week 26p-value: 0.149695% CI: [-19.59, 124.35]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza B/Yamagata at Day 28p-value: 0.904495% CI: [-296.57, 263.06]ANCOVA
Comparison: Titers of influenza-specific neutralizing antibodies against Influenza B/Yamagata at Week 26p-value: 0.419895% CI: [-56.97, 134.24]ANCOVA
Secondary
Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells)
The numbers of immunogenic Participants (with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were listed. The immunogenicity here was determined via the frequency of influenza-specific T-cells measured by IFN-γ/granzyme B ELISpot assay (enzyme linked immunospot) where the adjusted Spot Forming Units (SFU) per million PBMCs (peripheral blood mononuclear cells) after background subtraction (dimethyl sulfoxide, DMSO) were counted. The immunogenicity analyses were conducted only in the Immunology Analysis Set of Participants.
Time frame: Day 28 and Week 26
Population: The samples for this immunogenicity analysis were taken only from participants in the 2 Immunogenicity cohorts included in the MVA-NP+M1 Group vs the Placebo Group.~The immunogenicity analysis for Day 28 used 24 participant results from the MVA-NP+M1 Cohort and 24 participant results from the Placebo Cohort, as available.~The immunogenicity analysis for Week26 used 23 participant results from the MVA-NP+M1 Cohort and 25 participant results from the Placebo Cohort, as available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 Group | Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) | Participants with immunogenic response (as the frequency of influenza-specific T-cells) at Day 28 | 20 Participants |
| MVA-NP+M1 Group | Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) | Participants with Immunogenic response (via the frequency of influenza-specific T-cells) at Week 26 | 16 Participants |
| Saline Placebo Group | Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) | Participants with immunogenic response (as the frequency of influenza-specific T-cells) at Day 28 | 21 Participants |
| Saline Placebo Group | Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) | Participants with Immunogenic response (via the frequency of influenza-specific T-cells) at Week 26 | 13 Participants |
Comparison: Statistical analysis was performed for Total(NP+M) (SFU/10\^6 PBMC) at Day 28 Nucleoprotein = NP, matrix1 = M1p-value: 095% CI: [443.71, 1043.84]ANCOVA
Comparison: Statistical analysis was performed for Total(NP+M) (SFU/10\^6 PBMC) at Week 26 Nucleoprotein = NP, matrix1 = M1p-value: 0.067395% CI: [-13.14, 367.33]ANCOVA
Secondary
Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC
The severity of ILI was assessed by each participant completing of electronic Diaries for symptom severity daily for the following symptoms: Feeling hot, Temperature, Cough, Sore throat, Blocked nose, Chest pain, Muscle aches, Shortness of breath with their severities (scores) recorded as: Not Present (0), Mild (1), Moderate (2), Severe (3). For each symptom, the severity score was used to calculate the area under the curve (AUC), along with the calendar day, for the entire influenza season using trapezoidal rule. Participants could be followed for varying days in the influenza season, therefore the AUC will be time weighted to 168 days: Time weighted AUC=((raw AUC \[time in days\])/(number of days used for analysis)) \* 168
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MVA-NP+M1 Group | Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC | 5490 weighted days | Standard Deviation 23.4944 |
| Saline Placebo Group | Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC | 5297 weighted days | Standard Deviation 21.3996 |
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Feeling Hot (AUC)p-value: 0.95595% CI: [0.83, 1.19]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Temperature (AUC)p-value: 0.893395% CI: [1, 1]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Cough (AUC)p-value: 0.215695% CI: [0.7, 1.09]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Sore Throat AUCp-value: 0.221695% CI: [0.71, 1.1]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Blocked Nose AUCp-value: 0.230695% CI: [0.69, 1.09]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Chest Pain AUCp-value: 0.803895% CI: [0.97, 1.13]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Muscle Pain AUCp-value: 0.931995% CI: [0.84, 1.21]ANOVA
Comparison: Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Shortness of Breath AUCp-value: 0.839995% CI: [0.86, 1.19]ANOVA