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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MVA-NP+M1 & H3N2 Challenge Virus | Experimental | 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) |
|
| Saline Placebo & H3N2 Challenge Virus | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MVA-NP+M1 | Biological | Trial Vaccine |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 | Description | Time Frame |
|---|---|---|
| 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. | 9 days from day 2 to day 10 |
| Measure | Description | Time Frame |
|---|---|---|
| Severity of Individual Symptoms for MVA-NP+M1 vs. Placebo | Severity of individual self-reported symptoms for MVA-NP+M1 vs. Placebo | 11 days |
| Total Symptom Score Time to Start, Time to Peak and Duration |
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:
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:
EXCLUSION (CHALLENGE PERIOD ONLY)
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| Name | Affiliation | Role |
|---|---|---|
| Robin Rogiers, MD | SGS S.A. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SGS Life Sciences, Clinical Pharmacology Unit (CPU) | Antwerp | 2060 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38729196 | Derived | Evans TG, Castellino F, Kowalik Dobczyk M, Tucker G, Walley AM, Van Leuven K, Klein J, Rutkowski K, Ellis C, Eagling-Vose E, Treanor J, van Baalen C, Filkov E, Laurent C, Thacker J, Asher J, Donabedian A. Assessment of CD8+ T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study. Lancet Microbe. 2024 Jul;5(7):645-654. doi: 10.1016/S2666-5247(24)00024-7. Epub 2024 May 7. |
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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.
The study was conducted at the SGS Clinical Pharmacology Unit in Antwerp, Belgium.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Saline Placebo & H3N2 Challenge Virus |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | End point values | Posted | Least Squares Mean | 95% Confidence Interval | hour*Log10 Viral Particles/ ml | 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. |
|
Any time during the study from the first administration of any study drug until the last study-related activity (the outpatient visit at 27 days ±3 days following the challenge or 6 months following vaccination ±14 days, whichever is longer)
Treatment-emergent adverse events (TEAE) are defined as the Adverse Events starting during or after first administration of any study drug to the end of the study independently of their intensity and if they are related or not to the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MVA-NP+M1 (Vaccination Phase) | Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); MVA-NP+M1: Trial Vaccine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Foetal death | Pregnancy, puerperium and perinatal conditions | MedDRA (20.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tom Evans, MD | Vaccitech Ltd. | +44 01865 591 445 | enquiries@vaccitech.co.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 10, 2019 | Dec 4, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 15, 2020 | Dec 4, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| Saline |
| Biological |
Sodium Chloride Placebo |
|
| H3N2 (A/Belgium/2417/2015) | Biological | Challenge Agent |
|
| 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 | 9 days from day 2 to day 10 |
| 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 | 9 days from day 2 to day 10 |
| 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) | 9 days from day 2 to day 10 |
| 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) | 9 days from day 2 to day 10 |
| Peak Viral Shedding (qPCR) After the Virus Inoculation | This is measured by the highest viral load concentration by qPCR | 9 days from Day 2 to Day 10 |
| Peak Viral Shedding (qCulture) After Virus Inoculation | This is measured by the highest viral load concentration by qCulture. | 9 days from day 2 to day 10 |
| 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) | 9 days from day 2 to day 10 |
| 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) | 9 days from day 2 to day 10 |
| 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) | 9 days from day2 to day10 |
| 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) | 9 days from day 2 to day 10 |
| 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. | 11 days from Day 1 to Day 11 |
| Total Days of Fever | Total days of fever for MVA-NP+M1 vs. Placebo | 11 days from Day 1 to Day 11 |
| 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). | 11 days from Day 1 to Day 11 |
| 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. | 3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period) |
| 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 | 7 days following vaccination |
| 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 | 17 days following vaccination |
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).
| 11 days |
| Correlation of T Cell Phenotypes With Illness Outcomes | Correlation of antigen specific T Cell phenotypes with illness outcomes | 3 months |
| 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) | 3 months |
| Pregnancy |
|
| Adverse Event |
|
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Smoking Status | Count of Participants | Participants |
|
| Height | Median | Full Range | cm |
|
| Weight | Median | Full Range | kg |
|
| BMI | Median | Full Range | kg/m^2 |
|
| OG001 |
| Placebo (ITT) |
Intention-to-treat (the actually challenged with the virus) |
| OG002 | MVA-NP+M1 (PP) | Per protocol analysis set |
| OG003 | Placebo (PP) | Per protocol analysis set |
| OG004 | MVA-NP+M1 (Challenge) | Safety Analysis Set (challenged participants) |
| OG005 | Placebo (Challenge) | Safety Analysis Set (challenged participants) |
|
|
|
| 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. | Posted | Count of Participants | Participants | 9 days from day 2 to day 10 |
|
|
|
|
| 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 | Posted | Number | 95% Confidence Interval | percentage of participants | 9 days from day 2 to day 10 |
|
|
|
|
| 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 | Posted | Number | 95% Confidence Interval | percentage | 9 days from day 2 to day 10 |
|
|
|
|
| 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) | [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 | Posted | Median | 95% Confidence Interval | hours | 9 days from day 2 to day 10 |
|
|
|
|
| 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) | [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 | Posted | Median | 95% Confidence Interval | hours | 9 days from day 2 to day 10 |
|
|
|
|
| Secondary | Peak Viral Shedding (qPCR) After the Virus Inoculation | This is measured by the highest viral load concentration by qPCR | Posted | Mean | 95% Confidence Interval | Log10 Viral Particles/ ml | 9 days from Day 2 to Day 10 |
|
|
|
|
| Secondary | Peak Viral Shedding (qCulture) After Virus Inoculation | This is measured by the highest viral load concentration by qCulture. | Posted | Mean | 95% Confidence Interval | Log10 Viral Particles/ ml | 9 days from day 2 to day 10 |
|
|
|
|
| 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) | [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 | Posted | Median | 95% Confidence Interval | hours | 9 days from day 2 to day 10 |
|
|
|
|
| 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) | [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 | Posted | Median | 95% Confidence Interval | hours | 9 days from day 2 to day 10 |
|
|
|
|
| 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) | This endpoint is only calculated for the subset of participants with a successful attack. | Posted | Mean | 95% Confidence Interval | hours | 9 days from day2 to day10 |
|
|
|
| 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) | This endpoint is only calculated for the subset of participants with a successful attack | Posted | Mean | 95% Confidence Interval | hours | 9 days from day 2 to day 10 |
|
|
|
| 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. | Posted | Geometric Mean | 95% Confidence Interval | Composite symptom score on scale*hour | 11 days from Day 1 to Day 11 |
|
|
|
|
| Secondary | Total Days of Fever | Total days of fever for MVA-NP+M1 vs. Placebo | Posted | Mean | 95% Confidence Interval | days | 11 days from Day 1 to Day 11 |
|
|
|
|
| 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). | Total mucus production was only calculated for challenge cohorts 5 to 8 and only if all tissues (cleaned or used) were returned. | Posted | Mean | 95% Confidence Interval | grams | 11 days from Day 1 to Day 11 |
|
|
|
|
| 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. | Posted | Mean | Standard Deviation | Spot-forming units per million | 3 months (day 0, day 8 and day 28 of the vaccination period and day -1 and day 28 of the challenge period) |
|
|
|
| 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 | Safety Analysis Set | Posted | Count of Participants | Participants | 7 days following vaccination |
|
|
|
| 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 | Posted | Count of Participants | Participants | 17 days following vaccination |
|
|
|
| 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 | Not Posted | 11 days | Participants |
| 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). | Not Posted | 11 days | Participants |
| Other Pre-specified | Correlation of T Cell Phenotypes With Illness Outcomes | Correlation of antigen specific T Cell phenotypes with illness outcomes | Not Posted | 3 months | Participants |
| 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) | Not Posted | 3 months | Participants |
| 0 |
| 87 |
| 1 |
| 87 |
| 36 |
| 87 |
| EG001 | Saline Placebo (Vaccination Phase) | Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Saline: Sodium Chloride Placebo | 0 | 58 | 0 | 58 | 18 | 58 |
| EG002 | MVA-NP+M1 (Challenge Phase) | Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.); MVA-NP+M1: Trial Vaccine Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) | 0 | 71 | 0 | 71 | 30 | 71 |
| EG003 | Saline Placebo (Challenge Phase) | Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%); Saline: Sodium Chloride Placebo Challenge Virus administered: H3N2 (nasal spray, 0.5 ml, 1.0x10^6 TCID50/ml) | 0 | 47 | 1 | 47 | 21 | 47 |
| Acute Psychosis | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Oral Herpes | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dry Throat | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Regurgitation | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dizziness Postural | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Skin Irritation | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Flank Pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Musculoskeletal Stiffness | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Subcutaneous Haematoma | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Joint Injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Ligament Sprain | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Skin Wound | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Lacrimation Increased | Eye disorders | MedDRA (20.0) | Systematic Assessment |
|
| Swelling of Eyelid | Eye disorders | MedDRA (20.0) | Systematic Assessment |
|
| Eye Irritation | Eye disorders | MedDRA (20.0) | Systematic Assessment |
|
| Conjunctival Hyperaemia | Eye disorders | MedDRA (20.0) | Systematic Assessment |
|
| Ear Discomfort | Ear and labyrinth disorders | MedDRA (20.0) | Systematic Assessment |
|
| Inflammation | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Scar Excision | Surgical and medical procedures | MedDRA (20.0) | Systematic Assessment |
|
| Atrial Flutter | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
|
Not provided
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D017670 |
| Sodium Compounds |
| Day 28 (from Vaccination) |
|
| Day 0 Challenge Period |
|
| Day 28 Challenge Period |
|
| TEAE or solicited symptom |
|
| Local solicited symptom |
|
| Local Grade 3 solicited symptom |
|
| Systemic solicited symptom |
|
| Systemic Grade 3 solicited symptom |
|
| TEAE of special interest |
|
| Serious TEAE |
|
| Non-serious TEAE |
|
| Grade ≥3 TEAE |
|
| Grade ≥3 TE laboratory toxicity |
|
| Fatal TEAE |
|
| TEAE related to treatment |
|
| Serious TEAE related to treatment |
|
| Grade ≥3 TEAE related to treatment |
|
| TEAE for which the study was discontinued |
|
| TEAE or solicited symptom |
|
| Local solicited symptom |
|
| Local Grade 3 solicited symptom |
|
| Systemic solicited symptom |
|
| Systemic Grade 3 solicited symptom |
|
| TEAE of special interest |
|
| Serious TEAE |
|
| Non-serious TEAE |
|
| Grade ≥3 TEAE |
|
| Grade ≥3 TE laboratory toxicity |
|
| Fatal TEAE |
|
| TEAE related to challenge |
|
| Serious TEAE related to challenge |
|
| Grade ≥3 TEAE related to challenge |
|
| TEAE for which the study was discontinued |
|