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The trial is being stopped for futility. Season 2 cancelled.
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| Name | Class |
|---|---|
| Clinical Network Services (CNS) Pty Ltd | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MVA-NP+M1 | Experimental | Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.) |
|
| Saline Placebo | Placebo Comparator | Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MVA-NP+M1 | Biological | Trial Vaccine |
| |
| Saline |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| James Vandeleur, MD | Paratus Clinical Pty Ltd | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Paratus Clinical Pty Ltd | Blacktown | New South Wales | 2148 | Australia | ||
| Genesis Research Services |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35305317 | Derived | Evans TG, Bussey L, Eagling-Vose E, Rutkowski K, Ellis C, Argent C, Griffin P, Kim J, Thackwray S, Shakib S, Doughty J, Gillies J, Wu J, Druce J, Pryor M, Gilbert S. Efficacy and safety of a universal influenza A vaccine (MVA-NP+M1) in adults when given after seasonal quadrivalent influenza vaccine immunisation (FLU009): a phase 2b, randomised, double-blind trial. Lancet Infect Dis. 2022 Jun;22(6):857-866. doi: 10.1016/S1473-3099(21)00702-7. Epub 2022 Mar 16. |
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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.
The single-blind study was conducted at 9 sites across Australia, over one Influenza season.
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| ID | Title | Description |
|---|---|---|
| FG000 | MVA-NP+M1 Group (Main Cohort + Immunogenicity Cohort) | 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. |
| FG001 | Saline Placebo Group (Main Cohort+ Immunogenicity Cohort) | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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. | Posted | Count of Participants | Participants | 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. |
|
Unsolicited non-serious adverse events will be collected for 28 days post-vaccination. Hospitalisations, other serious adverse events and or adverse events of special interest will be collected for the duration of the influenza season. Solicited adverse events, including solicited local injection site reactions (ISR) and solicited systemic reactions, will be collected for 7 days post-vaccination. These will be recorded daily in the eDiary for all participants.
Adverse events were coded using MedDRA(most recent version). AEs are grouped by system organ class (SOC) and preferred term and summarized by vaccination group (MVA-NP+M1 Group vs Saline Placebo Group) at the time of AE onset. All AEs are reported for each group and the Immunogenicity cohorts (as parts of each group) did not influence the adverse events reporting style.
In the summary tables, adverse events are presented/summarized by decreasing frequency of Total Events overall within each SOC
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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 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 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 |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 20, 2019 | Jan 29, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 1, 2020 | Jan 29, 2021 | 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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| Drug |
Sodium Chloride Placebo |
|
|
| 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) |
| 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. | 7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October) |
| 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. | Day 28 and Week 26 |
| 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. | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) |
| 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 | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) |
| 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. | Day 28 and Week 26 |
| Broadmeadow |
| New South Wales |
| 2292 |
| Australia |
| Paratus Clinical Pty Ltd | Kanwal | New South Wales | 2259 | Australia |
| Scientia Clinical Research | Sydney | New South Wales | 2031 | Australia |
| University of Sunshine Coast (USC) | Morayfield | Queensland | 4506 | Australia |
| University of Sunshine Coast (USC) | Sippy Downs | Queensland | 4556 | Australia |
| Mater Research | South Brisbane | Queensland | 4101 | Australia |
| CMAX | Adelaide | South Australia | 5000 | Australia |
| Nucleus Network Pty Ltd | Melbourne | Victoria | 3004 | Australia |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| Body Temperature | Mean | Standard Deviation | degree Celsius |
|
| OG000 |
| 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. |
| OG001 | 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. |
|
|
|
| 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. | Posted | Count of Participants | Participants | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) |
|
|
|
|
| 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. | Safety Analysis Set | Posted | Count of Participants | Participants | 7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October) |
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Day 28 and Week 26 |
|
|
|
|
| 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. | 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. | Posted | Median | 95% Confidence Interval | days | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) |
|
|
|
|
| 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 | Posted | Mean | Standard Deviation | weighted days | 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) |
|
|
|
|
| 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. | 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. | Posted | Count of Participants | Participants | Day 28 and Week 26 |
|
|
|
|
| 0 |
| 1,077 |
| 18 |
| 1,077 |
| 524 |
| 1,077 |
| EG001 | 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 | 1,075 | 22 | 1,075 | 435 | 1,075 |
| Diverticulitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Infective exacerbation of chronic obstructive airways disease | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Lower respiratory tract infection viral | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Medical device site joint infection | Immune system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Pneumonia mycoplasmal | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Pyelonephritis acute | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| COPD | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cardiomyopathy | Cardiac disorders | MedDRA (20.0) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| Cholecystectomy | Surgical and medical procedures | MedDRA (20.0) | Systematic Assessment |
|
| Endometriosis ablation | Surgical and medical procedures | MedDRA (20.0) | Systematic Assessment |
|
| Hysterectomy | Surgical and medical procedures | MedDRA (20.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Bipolar disorder | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA (20.0) | Systematic Assessment |
|
| Adnexal torsion | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (20.0) | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA (20.0) | Systematic Assessment |
|
| Arthritis reactive | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (20.0) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (20.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (20.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (20.0) | Systematic Assessment |
|
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | Injury, poisoning and procedural complications | MedDRA (20.0) | Systematic Assessment |
|
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | Skin and subcutaneous tissue disorders | MedDRA (20.0) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (20.0) | Systematic Assessment |
|
| EAR AND LABYRINTH DISORDERS | Ear and labyrinth disorders | MedDRA (20.0) | Systematic Assessment |
|
| EYE DISORDERS | Eye disorders | MedDRA (20.0) | Systematic Assessment |
|
Not provided
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D017670 |
| Sodium Compounds |
| Poisson Model with Robust Variance |
| 0.9799 |
| Relative Risk |
| 1 |
| 2-Sided |
| 95 |
| 0.86 |
| 1.15 |
| Other |
| Participants with Solicited Local Injection Site Reaction (IRS) - Warmth |
|
| Participants with Solicited Local Injection Site Reaction (IRS) - Erythema |
|
| Participants with Severe, Solicited Local Injection Site Reaction |
|
| Participants with Solicited Systemic Reactions - Chills |
|
| Participants with Solicited Systemic Reactions - Myalgia |
|
| Participants with Solicited Systemic Reactions - Fatigue |
|
| Participants with Solicited Systemic Reactions - Headache |
|
| Participants with Solicited Systemic Reactions - Nausea |
|
| Participants with Solicited Systemic Reactions - Arthralgia |
|
| Participants with Solicited Systemic Reactions - Malaise |
|
| Participants with Solicited Systemic Reactions - Feverishness |
|
| Participants with Severe, Solicited Systemic Reaction |
|
| Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Week 26 |
|
|
| ANCOVA |
| 0.8468 |
| Least Squares Mean Difference |
| -13.39 |
| 2-Sided |
| 95 |
| -152.26 |
| 125.47 |
| Other |
| Titers of influenza-specific neutralizing antibodies against Influenza A/H3N2 (MN) at Day 28 | ANCOVA | 0.5087 | Least Squares Mean Difference | -465.7 | 2-Sided | 95 | -1875.21 | 943.75 | Other |
| Titers of influenza-specific neutralizing antibodies against Influenza A/H3N2 (MN) at Week 26 | ANCOVA | 0.7509 | Least Squares Mean Difference | -83.68 | 2-Sided | 95 | -611.67 | 444.32 | Other |
| Titers of influenza-specific neutralizing antibodies against Influenza A/H1N1pdm at Day 28 | ANOVA | 0.3398 | Least Squares Mean Difference | -81.17 | 2-Sided | 95 | -250.72 | 88.39 | Other |
| Titers of influenza-specific neutralizing antibodies against Influenza A/H1N1pdm at Week 26 | ANCOVA | 0.4154 | Least Squares Mean Difference | 26.15 | 2-Sided | 95 | -37.95 | 90.26 | Other |
| Titers of neutralizing antibodies against Influenza B/ Victoria at Day 28 | ANCOVA | 0.7193 | Least Squares Mean Difference | 22.84 | 2-Sided | 95 | -104.50 | 150.18 | Other |
| Titers of influenza-specific neutralizing antibodies against Influenza B/ Victoria at Week 26 | ANCOVA | 0.1496 | Least Squares Mean Difference | 52.38 | 2-Sided | 95 | -19.59 | 124.35 | Other |
| Titers of influenza-specific neutralizing antibodies against Influenza B/Yamagata at Day 28 | ANCOVA | 0.9044 | Least Squares Mean Difference | -16.76 | 2-Sided | 95 | -296.57 | 263.06 | Other |
| Titers of influenza-specific neutralizing antibodies against Influenza B/Yamagata at Week 26 | ANCOVA | 0.4198 | Least Squares Mean Difference | 38.64 | 2-Sided | 95 | -56.97 | 134.24 | Other |
| ANOVA |
| 0.8933 |
| Geometric Mean Ratio (Active vs Placebo) |
| 1 |
| 2-Sided |
| 95 |
| 1 |
| 1 |
| Other |
| Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Cough (AUC) | ANOVA | 0.2156 | Geometric Mean Ratio (Active vs Placebo) | 0.87 | 2-Sided | 95 | 0.7 | 1.09 | Other |
| Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Sore Throat AUC | ANOVA | 0.2216 | Geometric Mean Ratio (Active vs Placebo) | 0.88 | 2-Sided | 95 | 0.71 | 1.10 | Other |
| Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Blocked Nose AUC | ANOVA | 0.2306 | Geometric Mean Ratio (Active vs Placebo) | 0.87 | 2-Sided | 95 | 0.69 | 1.09 | Other |
| Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Chest Pain AUC | ANOVA | 0.8038 | Geometric Mean Ratio (Active vs Placebo) | 0.99 | 2-Sided | 95 | 0.97 | 1.13 | Other |
| Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Muscle Pain AUC | ANOVA | 0.9319 | Geometric Mean Ratio (Active vs Placebo) | 1.01 | 2-Sided | 95 | 0.84 | 1.21 | Other |
| Time Weight Area Under the Curve (AUC) for Symptoms of Influenza - Symptom: Shortness of Breath AUC | ANOVA | 0.8399 | Geometric Mean Ratio (Active vs Placebo) | 1.01 | 2-Sided | 95 | 0.86 | 1.19 | Other |
| Participants with Immunogenic response (via the frequency of influenza-specific T-cells) at Week 26 |
|
|
| ANCOVA |
| 0.0673 |
| Least Squares Mean Difference |
| 177.10 |
| 2-Sided |
| 95 |
| -13.14 |
| 367.33 |
| Other |