Influenza
Conditions
Brief summary
A Phase 2, single center, randomized, double blind study evaluating the safety, efficacy, and immunogenicity of MVA NP+M1 in the H3N2 human influenza challenge model; on healthy adult volunteers.
Detailed description
The study consists of an outpatient vaccination phase (155 participants), and at least 2 months later an inpatient challenge phase (134 participants). Participants are randomized 93:62 to receive either MVA-NP+M1 or Placebo. Up to 20 participants will be challenged over several 3-week blocks, and the remainder at the final 3-week block for a total of 80 MVA-NP+M1 and 54 Placebo recipients challenged.
Interventions
BIOLOGICALMVA-NP+M1
Trial Vaccine
BIOLOGICALSaline
Sodium Chloride Placebo
BIOLOGICALH3N2 (A/Belgium/2417/2015)
Challenge Agent
Sponsors
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment. * Non-smokers or those who stopped smoking ≥ 3 months prior to screening 1 visit. * Willingness to remain in isolation for the duration of the study. * A female participant is eligible for this study if she is not pregnant or breast feeding and 1 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 has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 6 months prior to vaccination to 6 months after administration of the influenza challenge virus. Highly effective methods of contraception include 1 or more of the following: i. male partner who is sterile (vasectomised) prior to the female participants entry into the study and is the sole sexual partner for the female participant; ii. hormonal (oral, intravaginal, transdermal, implantable or injectable); iii. an intrauterine hormone-releasing system (IUS); iv. an intrauterine device (IUD) with a documented failure rate of \< 1%; v. bilateral tubal occlusion. * Pre-challenge serum microneutralization test (MNT) against A/Belgium/4217/2015 (H3N2) challenge strain \< 20.
Exclusion criteria
* BMI \< 19 and \> 32. * Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness including a history of chronic respiratory illness. * History of seasonal hay fever or a clinically significant seasonal allergic rhinitis (SAR), including the use of symptomatic prescription only medication and non-prescription medication. * History or evidence of autoimmune disease or known immunodeficiency of any cause - with the exception of atopic dermatitis/eczema and atopic rhinitis. * Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be exacerbated by any component of the vaccine. * History of lung disease (Asthma, COPD). * Current smokers or those who stopped smoking \< 3months prior to screening 1 visit. * Positive diagnostic tests for HIV, Hepatitis B or Hepatitis C indicating active infection. * Evidence of drug abuse or a positive urine drug screen or alcohol breath test. * Chronic use of any medication or other product (prescription or over-the-counter), for symptoms of rhinitis or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of any intranasal medication for any indication that has not ceased within 30 days prior to screening 1. * Receipt of any investigational drug within 3 months prior to vaccination, or prior participation in a clinical trial of any influenza vaccine, or any investigational vaccine or experimental influenza viral challenge delivered directly to the respiratory tract within 1 year prior to challenge. * Receipt of the 2018/2019 seasonal flu vaccine. * Receipt of any live vaccines within the 4 weeks prior to vaccination. * Any laboratory test which is abnormal and which is deemed by the Investigator(s) to be clinically significant. * Receipt of any systemic chemotherapy agent at any time. * Physician reported influenza or a syndrome consistent with influenza (as judged by the investigator) in the previous 6 months. * Known allergy to treatments for influenza (including but not limited to oseltamivir). * History of frequent epistaxis (nose bleeds). * Any nasal or sinus surgery within 6 months of Viral Challenge or any significant abnormality, either of which results in alteration of the anatomy of the nose or nasopharynx (including significant nasal polyps). * Volunteers with household contacts who are at risk for serious or severe complications of influenza disease including, but not limited to: persons ≥ 65 years; presence of significant chronic cardiopulmonary, metabolic, renal, or neurological conditions; immunosuppression due to any condition or therapies; BMI \>40. * Participants that are an employee or family member of the Investigator or study site personnel may not be enrolled. * Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study. EXCLUSION (CHALLENGE PERIOD ONLY) * Abnormal spirometry assessed to be clinically significant. * Known close contact with anyone known to have influenza in the past 7 days at the time of quarantine. * Influenza-like illness (ILI) symptoms as assessed at the admission to clinic on Day -2 prior to challenge. * Presence of fever, defined as participant presenting with a temperature reading of \> 38.0°C on admission to quarantine. * Qualitative Polymerase chain reaction (PCR) results positive for viral infection. However, participants may be included into later challenge cohort. * Acute use of any medication or other product, prescription or over-the-counter, for symptoms of rhinitis or nasal congestion within 7 days prior to challenge. This includes any oral corticosteroid or beta agonist containing nasal spray.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | Throughout 9 days (Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10) after viral Inoculation (Day1) of the challenge phase. Nasal swabs taken twice a day (b.i.d) at least 8 hours apart. | Measure of nasopharyngeal viral shedding during challenge; recorded as viral area under curve (vAUC) as determined by quantitative real time polymerase chain reaction (qRT-PCR). vAUC is calculated by plotting the log viral particles number/ml for each time point against time and is using the trapezoidal rule. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation | 9 days from day 2 to day 10 | This is calculated as (datetime of highest viral load concentration (qPCR) - challenge datetime)/(60\*60) |
| Average Total Mucus Production | 11 days from Day 1 to Day 11 | Total mucus weight of used tissue (regardless of take rate) for MVA-NP+M1 vs. Placebo. Total mucus production was only be calculated in case all tissues were returned (sum of clean and used tissues returned should be 20 tissues for each bag). |
| T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | 3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period) | T Cell Response was assessed for IFN gamma and granzyme B, on the peripheral blood mononuclear cell using a double-colour enzymatic ELISpot assay. For each of them, three stimulation antigens were assessed: nucleoprotein NP, matrix1 M1 and a negative control, dimethyl sulfoxide (DMSO). The number of spot-forming T cell colonies per well (i.e. 200,000 cells) +/- standard deviation for the total response to NP+M1 is reported. The endpoint was recorded as the mean spot-forming units per million peripheral blood mononuclear cells in the peptide-stimulated wells minus the mean DMSO control wells for the sample. T cell responses over time (sampling timepoints) were then assessed in relation to the primary endpoint, symptom scores, and influenza incidence. |
| Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | 7 days following vaccination | Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination; self-reported symptoms recorded using paper diaries |
| Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | 17 days following vaccination | Occurrence of solicited local and systemic reactogenicity signs and symptoms; self-reported symptoms recorded using questionnaires and adverse event monitoring |
| Number and Percentage of Virologically Confirmed Influenza-Like Illness | 9 days from day 2 to day 10 | Incidence (frequency tabulation) of laboratory-confirmed influenza-like illness compared between vaccine and placebo arms Virologically confirmed influenza-like illness (ILI) is defined as having respiratory or flu-like symptom occurring on two consecutive days, along with a positive qPCR or qCulture result. |
| Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR) | 9 days from day 2 to day 10 | The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qRT-PCR within the timespan of two consecutive days |
| Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture) | 9 days from day 2 to day 10 | The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qCulture within the timespan of two consecutive days |
| Time to Start of Viral Shedding (qPCR) From Virus Inoculation | 9 days from day 2 to day 10 | The Time to Start of Viral Shedding (qPCR) is calculated as (datetime of first of two positive swabs (qPCR) within 2 consecutive days - challenge datetime)/(60\*60) |
| Time to Start of Viral Shedding (qCulture) From Virus Inoculation | 9 days from day 2 to day 10 | Time to Start of Viral Shedding (qCulture) is calculated as (datetime of first of two positive swabs (qCulture) within 2 consecutive days - challenge datetime)/(60\*60) |
| Peak Viral Shedding (qPCR) After the Virus Inoculation | 9 days from Day 2 to Day 10 | This is measured by the highest viral load concentration by qPCR |
| Peak Viral Shedding (qCulture) After Virus Inoculation | 9 days from day 2 to day 10 | This is measured by the highest viral load concentration by qCulture. |
| Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation | 9 days from day 2 to day 10 | This is calculated as (datetime of highest viral load concentration (qCulture) - challenge datetime)/(60\*60) |
| Duration of Viral Shedding (qPCR) After the Virus Inoculation | 9 days from day2 to day10 | It is calculated as (datetime of first negative swab (qPCR) following the last positive swab (qPCR) - datetime of first positive of two positive swabs (qPCR) within 2 consecutive days)/(60\*60) |
| Duration of Viral Shedding (qCulture) After the Virus Inoculation | 9 days from day 2 to day 10 | It is calculated as (datetime of first negative swab (qCulture) following the last positive swab (qCulture) - datetime of first positive of two positive swabs (qCulture) within 2 consecutive days)/(60\*60) |
| Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC) | 11 days from Day 1 to Day 11 | Total symptom scores were compared for MVA-NP+M1 vs. Placebo from Day1 to Day11 post-challenge as AUC of composite score. Symptoms were collected twice a day (lymphadenopathy once a day) on a Symptom Score Card(SSC). SSC recorded scores for each 16 general (gastrointestinal/body systemic) and 12 local (upper/lower respiratory tract) symptoms, on the scale per timepoint (for example Day2,AM). Participants rated the severity of symptoms, higher scores indicating a more severe symptom. The scores ranged from 0 to 3 (0:symptom free, 1:mild, 2:moderate, 3:severe).The SSC also contained the question whether the subject felt well to go to work today (yes/no). The Overall SSC score was calculated, as the Arithmetic Mean of the Scores collected across all 28 items on the card per Timepoint and ranged from 0 to maximum 3. The SSC AUC \[0-11 days\] was derived based on the Overall SSC score against time (\*hour), using the linear trapezoidal rule and it ranged from 0 to 110 Score\*hour. |
| Total Days of Fever | 11 days from Day 1 to Day 11 | Total days of fever for MVA-NP+M1 vs. Placebo |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation of T Cell Phenotypes With Illness Outcomes | 3 months | Correlation of antigen specific T Cell phenotypes with illness outcomes |
| Vaccination Effect on Antibody Responses by ELISpot and ICS Assays | 3 months | Antibody responses of MVA-NP+M1 vs Placebo following influenza challenge measured by ELISpot and Intracellular Cytokine Staining (ICS) |
| Total Symptom Score Time to Start, Time to Peak and Duration | 11 days | Time to start; time to peak and duration of total self-reported symptom score, regardless of take rate Influenza Symptom Score Card of FLU010 - Solicited symptoms for generalized, and upper and lower respiratory tract symptoms scored by severity (0: absent, 1: mild, 2: moderate, or 3: severe). |
| Severity of Individual Symptoms for MVA-NP+M1 vs. Placebo | 11 days | Severity of individual self-reported symptoms for MVA-NP+M1 vs. Placebo |
Countries
Belgium
Participant flow
Recruitment details
The study was conducted at the SGS Clinical Pharmacology Unit in Antwerp, Belgium.
Pre-assignment details
Eight-hundred and nineteen (819) subjects were screened. One hundred and forty-five (145) subjects were actually enrolled and vaccinated. The study consisted of an outpatient vaccination phase and at least 6 weeks later an inpatient challenge phase.
Participants by arm
| Arm | Count |
|---|---|
| MVA-NP+M1 & H3N2 Challenge Virus Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10\^8 pfu.); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10\^6 TCID50/ml)
MVA-NP+M1: Trial Vaccine
H3N2 (A/Belgium/2417/2015): Challenge Agent | 87 |
| Saline Placebo & H3N2 Challenge Virus Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10\^6 TCID50/ml)
Saline: Sodium Chloride Placebo
H3N2 (A/Belgium/2417/2015): Challenge Agent | 58 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Challenge Criteria Not Met / Sponsor Decision | 9 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | MVA-NP+M1 & H3N2 Challenge Virus | Saline Placebo & H3N2 Challenge Virus | 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 | 87 Participants | 58 Participants | 145 Participants |
| Age, Continuous | 43.00 years | 41.25 years | 42.50 years |
| BMI | 24.7 kg/m^2 | 25.5 kg/m^2 | 24.90 kg/m^2 |
| Height | 172.40 cm | 172.30 cm | 172.40 cm |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Middle Eastern | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 81 Participants | 57 Participants | 138 Participants |
| Region of Enrollment Belgium | 87 participants | 58 participants | 145 participants |
| Sex: Female, Male Female | 47 Participants | 31 Participants | 78 Participants |
| Sex: Female, Male Male | 40 Participants | 27 Participants | 67 Participants |
| Smoking Status Ex-smoker | 27 Participants | 18 Participants | 45 Participants |
| Smoking Status Non-smoker | 60 Participants | 40 Participants | 100 Participants |
| Weight | 72.9 kg | 75.15 kg | 73.60 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 58 | 0 / 71 | 0 / 47 |
| other Total, other adverse events | 36 / 87 | 18 / 58 | 30 / 71 | 21 / 47 |
| serious Total, serious adverse events | 1 / 87 | 0 / 58 | 0 / 71 | 1 / 47 |
Outcome results
Primary
Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR
Measure of nasopharyngeal viral shedding during challenge; recorded as viral area under curve (vAUC) as determined by quantitative real time polymerase chain reaction (qRT-PCR). vAUC is calculated by plotting the log viral particles number/ml for each time point against time and is using the trapezoidal rule.
Time frame: Throughout 9 days (Day2, Day3, Day4, Day5, Day6, Day7, Day8, Day9, Day10) after viral Inoculation (Day1) of the challenge phase. Nasal swabs taken twice a day (b.i.d) at least 8 hours apart.
Population: End point values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | 649.7 hour*Log10 Viral Particles/ ml |
| Placebo (ITT) | Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | 726.1 hour*Log10 Viral Particles/ ml |
| MVA-NP+M1 (PP) | Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | 646.5 hour*Log10 Viral Particles/ ml |
| Placebo (PP) | Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | 726.1 hour*Log10 Viral Particles/ ml |
| MVA-NP+M1 (Challenge) | Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | 649.7 hour*Log10 Viral Particles/ ml |
| Placebo (Challenge) | Degree of Nasopharyngeal Viral Shedding as Determined by Quantitative Polymerase Chain Reaction qPCR | 726.1 hour*Log10 Viral Particles/ ml |
p-value: 0.1711Wilcoxon (Mann-Whitney)
p-value: 0.1654Wilcoxon (Mann-Whitney)
p-value: 0.1711Wilcoxon (Mann-Whitney)
Secondary
Average Total Mucus Production
Total mucus weight of used tissue (regardless of take rate) for MVA-NP+M1 vs. Placebo. Total mucus production was only be calculated in case all tissues were returned (sum of clean and used tissues returned should be 20 tissues for each bag).
Time frame: 11 days from Day 1 to Day 11
Population: Total mucus production was only calculated for challenge cohorts 5 to 8 and only if all tissues (cleaned or used) were returned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Average Total Mucus Production | 31.09 grams |
| Placebo (ITT) | Average Total Mucus Production | 38.21 grams |
p-value: 0.5911Wilcoxon (Mann-Whitney)
Secondary
Duration of Viral Shedding (qCulture) After the Virus Inoculation
It is calculated as (datetime of first negative swab (qCulture) following the last positive swab (qCulture) - datetime of first positive of two positive swabs (qCulture) within 2 consecutive days)/(60\*60)
Time frame: 9 days from day 2 to day 10
Population: This endpoint is only calculated for the subset of participants with a successful attack
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Duration of Viral Shedding (qCulture) After the Virus Inoculation | 118.19 hours |
| Placebo (ITT) | Duration of Viral Shedding (qCulture) After the Virus Inoculation | 121.78 hours |
Secondary
Duration of Viral Shedding (qPCR) After the Virus Inoculation
It is calculated as (datetime of first negative swab (qPCR) following the last positive swab (qPCR) - datetime of first positive of two positive swabs (qPCR) within 2 consecutive days)/(60\*60)
Time frame: 9 days from day2 to day10
Population: This endpoint is only calculated for the subset of participants with a successful attack.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Duration of Viral Shedding (qPCR) After the Virus Inoculation | 170.80 hours |
| Placebo (ITT) | Duration of Viral Shedding (qPCR) After the Virus Inoculation | 172.47 hours |
Secondary
Number and Percentage of Virologically Confirmed Influenza-Like Illness
Incidence (frequency tabulation) of laboratory-confirmed influenza-like illness compared between vaccine and placebo arms Virologically confirmed influenza-like illness (ILI) is defined as having respiratory or flu-like symptom occurring on two consecutive days, along with a positive qPCR or qCulture result.
Time frame: 9 days from day 2 to day 10
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 (ITT) | Number and Percentage of Virologically Confirmed Influenza-Like Illness | Virologically confirmed Influenza-like Illness | 43 Participants |
| MVA-NP+M1 (ITT) | Number and Percentage of Virologically Confirmed Influenza-Like Illness | No Virologically Confirmed Influenza-like Illness | 28 Participants |
| Placebo (ITT) | Number and Percentage of Virologically Confirmed Influenza-Like Illness | Virologically confirmed Influenza-like Illness | 29 Participants |
| Placebo (ITT) | Number and Percentage of Virologically Confirmed Influenza-Like Illness | No Virologically Confirmed Influenza-like Illness | 18 Participants |
Comparison: The statistical analysis applies to participants with Virologically confirmed Influenza-like Illness versus participants without Virologically confirmed Influenza-like Illnessp-value: 1Fisher Exact
Secondary
Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms
Occurrence of solicited local and systemic reactogenicity signs and symptoms; self-reported symptoms recorded using questionnaires and adverse event monitoring
Time frame: 17 days following vaccination
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Solicited symptom | 62 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Non-serious TEAE | 30 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic solicited symptom | 45 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local solicited symptom | 59 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TE laboratory toxicity | 7 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic Grade 3 solicited symptom | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Fatal TEAE | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE or solicited symptom | 65 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE related to challenge | 7 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE of special interest | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE related to challenge | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local Grade 3 solicited symptom | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE related to challenge | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE for which the study was discontinued | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE | 30 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE for which the study was discontinued | 1 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE | 21 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Solicited symptom | 40 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE or solicited symptom | 42 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local solicited symptom | 39 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local Grade 3 solicited symptom | 0 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic solicited symptom | 32 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic Grade 3 solicited symptom | 0 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE of special interest | 0 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE | 1 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Non-serious TEAE | 20 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE | 2 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TE laboratory toxicity | 2 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Fatal TEAE | 0 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE related to challenge | 5 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE related to challenge | 0 Participants |
| Placebo (ITT) | Number of Participants With H3N2 Challenge Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE related to challenge | 0 Participants |
Secondary
Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms
Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination; self-reported symptoms recorded using paper diaries
Time frame: 7 days following vaccination
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Solicited symptom | 84 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Non-serious TEAE | 36 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic solicited symptom | 72 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE | 1 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local solicited symptom | 80 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TE laboratory toxicity | 2 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic Grade 3 solicited symptom | 2 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Fatal TEAE | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE or solicited symptom | 85 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE related to treatment | 10 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE of special interest | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE related to treatment | 1 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local Grade 3 solicited symptom | 2 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE related to treatment | 1 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE | 1 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE for which the study was discontinued | 0 Participants |
| MVA-NP+M1 (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE | 36 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE for which the study was discontinued | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE | 18 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Solicited symptom | 24 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE or solicited symptom | 34 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local solicited symptom | 8 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Local Grade 3 solicited symptom | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic solicited symptom | 20 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Systemic Grade 3 solicited symptom | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE of special interest | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Non-serious TEAE | 18 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TE laboratory toxicity | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Fatal TEAE | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | TEAE related to treatment | 4 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Serious TEAE related to treatment | 0 Participants |
| Placebo (ITT) | Number of Participants With MVA-NP+M1 Vaccination Related Adverse Events and Symptoms, Measured by Self-reported Symptoms | Grade ≥3 TEAE related to treatment | 0 Participants |
Secondary
Peak Viral Shedding (qCulture) After Virus Inoculation
This is measured by the highest viral load concentration by qCulture.
Time frame: 9 days from day 2 to day 10
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Peak Viral Shedding (qCulture) After Virus Inoculation | 4.073 Log10 Viral Particles/ ml |
| Placebo (ITT) | Peak Viral Shedding (qCulture) After Virus Inoculation | 4.069 Log10 Viral Particles/ ml |
p-value: 0.6753Wilcoxon (Mann-Whitney)
Secondary
Peak Viral Shedding (qPCR) After the Virus Inoculation
This is measured by the highest viral load concentration by qPCR
Time frame: 9 days from Day 2 to Day 10
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Peak Viral Shedding (qPCR) After the Virus Inoculation | 5.876 Log10 Viral Particles/ ml |
| Placebo (ITT) | Peak Viral Shedding (qPCR) After the Virus Inoculation | 6.054 Log10 Viral Particles/ ml |
p-value: 0.5485Wilcoxon (Mann-Whitney)
Secondary
Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR)
The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qRT-PCR within the timespan of two consecutive days
Time frame: 9 days from day 2 to day 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MVA-NP+M1 (ITT) | Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR) | qPCR-confirmed influenza | 90.1 percentage of participants |
| MVA-NP+M1 (ITT) | Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR) | No qPCR influenza | 9.9 percentage of participants |
| Placebo (ITT) | Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR) | qPCR-confirmed influenza | 97.9 percentage of participants |
| Placebo (ITT) | Percentage of Participants With Attack Rate of Challenge Agent (qRT-PCR) | No qPCR influenza | 2.1 percentage of participants |
Comparison: This statistical analysis applies to participants with qPCR confirmed Influenza versus participants with no qPCR confirmed Influenzap-value: 0.143Fisher Exact
Secondary
Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture)
The attack rate is defined as the percentage of inoculated participants with at least two consecutive positive swabs as determined by qCulture within the timespan of two consecutive days
Time frame: 9 days from day 2 to day 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MVA-NP+M1 (ITT) | Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture) | qCulture confirmed influenza | 77.5 percentage |
| MVA-NP+M1 (ITT) | Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture) | No qCulture-confirmed influenza | 22.5 percentage |
| Placebo (ITT) | Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture) | qCulture confirmed influenza | 85.1 percentage |
| Placebo (ITT) | Percentage of Participants With Quantitative Culture Attack Rate of Challenge Agent (qCulture) | No qCulture-confirmed influenza | 14.9 percentage |
Comparison: This statistical analysis applies to participants with qCulture confirmed Influenza versus participants without qCulture confirmed Influenzap-value: 0.3504Fisher Exact
Secondary
T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence
T Cell Response was assessed for IFN gamma and granzyme B, on the peripheral blood mononuclear cell using a double-colour enzymatic ELISpot assay. For each of them, three stimulation antigens were assessed: nucleoprotein NP, matrix1 M1 and a negative control, dimethyl sulfoxide (DMSO). The number of spot-forming T cell colonies per well (i.e. 200,000 cells) +/- standard deviation for the total response to NP+M1 is reported. The endpoint was recorded as the mean spot-forming units per million peripheral blood mononuclear cells in the peptide-stimulated wells minus the mean DMSO control wells for the sample. T cell responses over time (sampling timepoints) were then assessed in relation to the primary endpoint, symptom scores, and influenza incidence.
Time frame: 3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MVA-NP+M1 (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 8 (from Vaccination) | 645 Spot-forming units per million | Standard Deviation 634 |
| MVA-NP+M1 (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 0 Challenge Period | 460 Spot-forming units per million | Standard Deviation 471 |
| MVA-NP+M1 (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 28 (from Vaccination) | 566 Spot-forming units per million | Standard Deviation 551 |
| MVA-NP+M1 (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 28 Challenge Period | 561 Spot-forming units per million | Standard Deviation 483 |
| MVA-NP+M1 (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Baseline (Vaccination) | 230 Spot-forming units per million | Standard Deviation 265 |
| Placebo (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 28 Challenge Period | 329 Spot-forming units per million | Standard Deviation 220 |
| Placebo (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Baseline (Vaccination) | 167 Spot-forming units per million | Standard Deviation 157 |
| Placebo (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 8 (from Vaccination) | 170 Spot-forming units per million | Standard Deviation 144 |
| Placebo (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 28 (from Vaccination) | 163 Spot-forming units per million | Standard Deviation 160 |
| Placebo (ITT) | T Cell Responses as Defined by ELISpot Assay in Relation to the Primary Endpoint, Symptom Scores and Influenza Incidence | Day 0 Challenge Period | 159 Spot-forming units per million | Standard Deviation 132 |
Secondary
Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation
This is calculated as (datetime of highest viral load concentration (qCulture) - challenge datetime)/(60\*60)
Time frame: 9 days from day 2 to day 10
Population: \[MVA-NP+M1 (ITT)\] - Subjects assessed = 71 Subjects with event = 55 Subjects censored = 16; \[Placebo (ITT)\] - Subjects assessed = 47 Subjects with event = 40 Subjects censored = 7
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation | 83.40 hours |
| Placebo (ITT) | Time to Peak of Viral Shedding (qCulture) From the Viral Inoculation | 83.80 hours |
p-value: 0.4689Log Rank
Secondary
Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation
This is calculated as (datetime of highest viral load concentration (qPCR) - challenge datetime)/(60\*60)
Time frame: 9 days from day 2 to day 10
Population: \[MVA-NP+M1 (ITT)\] - Subjects assessed = 71 Subjects with event = 64 Subjects censored = 7; \[Placebo (ITT)\] - Subjects assessed = 47 Subjects with event = 46 Subjects censored = 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation | 72.20 hours |
| Placebo (ITT) | Time to Peak of Viral Shedding (qPCR) From the Viral Inoculation | 107.90 hours |
p-value: 0.711Log Rank
Secondary
Time to Start of Viral Shedding (qCulture) From Virus Inoculation
Time to Start of Viral Shedding (qCulture) is calculated as (datetime of first of two positive swabs (qCulture) within 2 consecutive days - challenge datetime)/(60\*60)
Time frame: 9 days from day 2 to day 10
Population: \[MVA-NP+M1(ITT)\] - Subjects assessed = 71 Subjects with event = 55 Subjects censored = 16; \[Placebo (ITT)\] - Subjects assessed = 47 Subjects with event = 40 Subjects censored = 7
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Time to Start of Viral Shedding (qCulture) From Virus Inoculation | 35.9 hours |
| Placebo (ITT) | Time to Start of Viral Shedding (qCulture) From Virus Inoculation | 47.6 hours |
p-value: 0.6534Log Rank
Secondary
Time to Start of Viral Shedding (qPCR) From Virus Inoculation
The Time to Start of Viral Shedding (qPCR) is calculated as (datetime of first of two positive swabs (qPCR) within 2 consecutive days - challenge datetime)/(60\*60)
Time frame: 9 days from day 2 to day 10
Population: \[MVA-NP+M1 (ITT)\] - subjects assessed = 71 subjects with event = 64 subjects censored = 7 \[Placebo (ITT)\] - subjects assessed = 47 subjects with event = 46 subjects censored = 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Time to Start of Viral Shedding (qPCR) From Virus Inoculation | 24.40 hours |
| Placebo (ITT) | Time to Start of Viral Shedding (qPCR) From Virus Inoculation | 24.30 hours |
p-value: 0.5558Log Rank
Secondary
Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC)
Total symptom scores were compared for MVA-NP+M1 vs. Placebo from Day1 to Day11 post-challenge as AUC of composite score. Symptoms were collected twice a day (lymphadenopathy once a day) on a Symptom Score Card(SSC). SSC recorded scores for each 16 general (gastrointestinal/body systemic) and 12 local (upper/lower respiratory tract) symptoms, on the scale per timepoint (for example Day2,AM). Participants rated the severity of symptoms, higher scores indicating a more severe symptom. The scores ranged from 0 to 3 (0:symptom free, 1:mild, 2:moderate, 3:severe).The SSC also contained the question whether the subject felt well to go to work today (yes/no). The Overall SSC score was calculated, as the Arithmetic Mean of the Scores collected across all 28 items on the card per Timepoint and ranged from 0 to maximum 3. The SSC AUC \[0-11 days\] was derived based on the Overall SSC score against time (\*hour), using the linear trapezoidal rule and it ranged from 0 to 110 Score\*hour.
Time frame: 11 days from Day 1 to Day 11
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC) | 16.709 Composite symptom score on scale*hour |
| Placebo (ITT) | Total Area Under the Curve (AUC) of Self-reported Influenza Total Symptom Score (SSC AUC) | 20.432 Composite symptom score on scale*hour |
p-value: 0.5001Wilcoxon (Mann-Whitney)
Secondary
Total Days of Fever
Total days of fever for MVA-NP+M1 vs. Placebo
Time frame: 11 days from Day 1 to Day 11
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MVA-NP+M1 (ITT) | Total Days of Fever | 0.0 days |
| Placebo (ITT) | Total Days of Fever | 0.0 days |
p-value: 0.6799zero-inflated poisson model
Other Pre-specified
Correlation of T Cell Phenotypes With Illness Outcomes
Correlation of antigen specific T Cell phenotypes with illness outcomes
Time frame: 3 months
Other Pre-specified
Severity of Individual Symptoms for MVA-NP+M1 vs. Placebo
Severity of individual self-reported symptoms for MVA-NP+M1 vs. Placebo
Time frame: 11 days
Other Pre-specified
Total Symptom Score Time to Start, Time to Peak and Duration
Time to start; time to peak and duration of total self-reported symptom score, regardless of take rate Influenza Symptom Score Card of FLU010 - Solicited symptoms for generalized, and upper and lower respiratory tract symptoms scored by severity (0: absent, 1: mild, 2: moderate, or 3: severe).
Time frame: 11 days
Other Pre-specified
Vaccination Effect on Antibody Responses by ELISpot and ICS Assays
Antibody responses of MVA-NP+M1 vs Placebo following influenza challenge measured by ELISpot and Intracellular Cytokine Staining (ICS)
Time frame: 3 months