Trial Outcomes & Findings for Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults (NCT NCT03880474)

Last Updated: 2021-04-26

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2364 participants

Primary outcome timeframe

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.

Results posted on

2021-04-26

Participant Flow

The single-blind study was conducted at 9 sites across Australia, over one Influenza season.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	1077	1075
Overall Study COMPLETED	1054	1055
Overall Study NOT COMPLETED	23	20

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MVA-NP+M1 Group n=1077 Participants 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.	Saline Placebo Group n=1075 Participants 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.	Total n=2152 Participants Total of all reporting groups
Age, Continuous	43.6 years STANDARD_DEVIATION 18.93 • n=5 Participants	43.8 years STANDARD_DEVIATION 18.40 • n=7 Participants	43.7 years STANDARD_DEVIATION 18.66 • n=5 Participants
Sex/Gender, Customized Female	631 Participants n=5 Participants	631 Participants n=7 Participants	1262 Participants n=5 Participants
Sex/Gender, Customized Male	445 Participants n=5 Participants	443 Participants n=7 Participants	888 Participants n=5 Participants
Sex/Gender, Customized Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1061 Participants n=5 Participants	1052 Participants n=7 Participants	2113 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	143 Participants n=5 Participants	118 Participants n=7 Participants	261 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	882 Participants n=5 Participants	892 Participants n=7 Participants	1774 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	29 Participants n=5 Participants	42 Participants n=7 Participants	71 Participants n=5 Participants
Body Mass Index (BMI)	28.36 kg/m^2 STANDARD_DEVIATION 6.727 • n=5 Participants	28.26 kg/m^2 STANDARD_DEVIATION 6.143 • n=7 Participants	28.31 kg/m^2 STANDARD_DEVIATION 6.435 • n=5 Participants
Body Temperature	36.44 degree Celsius STANDARD_DEVIATION 0.420 • n=5 Participants	36.44 degree Celsius STANDARD_DEVIATION 0.401 • n=7 Participants	36.44 degree Celsius STANDARD_DEVIATION 0.410 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=1077 Participants 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.	Saline Placebo Group n=1075 Participants 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.
Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). Participants with laboratory confirmed influenza using RT-PCR	35 Participants	23 Participants
Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). Participants without laboratory confirmed influenza using RT-PCR	1042 Participants	1052 Participants

SECONDARY outcome

Timeframe: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)

ILI is defined as feeling feverish or having a fever (feeling feverish or having a fever (≥37.8Celsius)) and at least one of the following symptoms: cough, sore throat. The incidence rate of ILI by the participant completing of eDiaries will be estimated for each vaccine group. The 95% CI for the incidence will be estimated by mid-p exact method. The difference in incidence between groups will be compared by Fisher's exact method.

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=1077 Participants 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.	Saline Placebo Group n=1075 Participants 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.
Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary Positive ILI Cases	273 Participants	273 Participants
Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary Negative ILI Cases	804 Participants	802 Participants

SECONDARY outcome

Timeframe: 7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October)

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=1077 Participants 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.	Saline Placebo Group n=1075 Participants 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.
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Local Injection Site Reaction (IRS) - Pain	292 Participants	19 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Local Injection Site Reaction (IRS) - Induration	113 Participants	4 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Local Injection Site Reaction (IRS) - Warmth	205 Participants	18 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Local Injection Site Reaction (IRS) - Erythema	198 Participants	15 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Severe, Solicited Local Injection Site Reaction	12 Participants	1 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Chills	61 Participants	18 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Myalgia	256 Participants	85 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Fatigue	248 Participants	117 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Headache	238 Participants	106 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Nausea	88 Participants	31 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Arthralgia	156 Participants	57 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Malaise	273 Participants	139 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Solicited Systemic Reactions - Feverishness	214 Participants	93 Participants
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs) Participants with Severe, Solicited Systemic Reaction	45 Participants	14 Participants

SECONDARY outcome

Timeframe: Day 28 and Week 26

Population: The samples for immunogenicity analysis were taken only from participants in the 2 Immunogenicity cohorts included in the MVA-NP+M1 Group vs the Placebo Group. The immunogenicity analysis for Day 28 used a number of 24 participant results from the MVA-NP+M1 Cohort and a number of 24 participant results from the Placebo Cohort. The immunogenicity analysis for Week26 used a number of 23 participant results from the MVA-NP+M1 Cohort and a number of 25 participant results from the Placebo Cohort.

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.

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=25 Participants 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.	Saline Placebo Group n=25 Participants 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.
Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Day 28	23 Participants	24 Participants
Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies) Participants with Influenza Antibody Titer: ANCOVA Analysis Immunology, at Week 26	23 Participants	25 Participants

SECONDARY outcome

Timeframe: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)

Population: ILI duration analysis is only applicable for ILI positive participants. In the MVA-NP+M1 Group there were 273 ILI positive participants assessed: 247 with event and 26 censored; In the Placebo Group there were 273 ILI positive participants assessed: 248 with event and 25 censored.

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.

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=273 Participants 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.	Saline Placebo Group n=273 Participants 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.
Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary	3 days Interval 3.0 to 4.0	3 days Interval 3.0 to 4.0

SECONDARY outcome

Timeframe: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)

The severity of ILI was assessed by each participant completing of electronic Diaries for symptom severity daily for the following symptoms: Feeling hot, Temperature, Cough, Sore throat, Blocked nose, Chest pain, Muscle aches, Shortness of breath with their severities (scores) recorded as: Not Present (0), Mild (1), Moderate (2), Severe (3). For each symptom, the severity score was used to calculate the area under the curve (AUC), along with the calendar day, for the entire influenza season using trapezoidal rule. Participants could be followed for varying days in the influenza season, therefore the AUC will be time weighted to 168 days: Time weighted AUC=((raw AUC \[time in days\])/(number of days used for analysis)) \* 168

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=1077 Participants 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.	Saline Placebo Group n=1075 Participants 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.
Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC	5490 weighted days Standard Deviation 23.4944	5297 weighted days Standard Deviation 21.3996

SECONDARY outcome

Timeframe: Day 28 and Week 26

Population: The samples for this immunogenicity analysis were taken only from participants in the 2 Immunogenicity cohorts included in the MVA-NP+M1 Group vs the Placebo Group. The immunogenicity analysis for Day 28 used 24 participant results from the MVA-NP+M1 Cohort and 24 participant results from the Placebo Cohort, as available. The immunogenicity analysis for Week26 used 23 participant results from the MVA-NP+M1 Cohort and 25 participant results from the Placebo Cohort, as available.

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.

Outcome measures

Outcome measures
Measure	MVA-NP+M1 Group n=25 Participants 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.	Saline Placebo Group n=25 Participants 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.
Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) Participants with immunogenic response (as the frequency of influenza-specific T-cells) at Day 28	20 Participants	21 Participants
Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells) Participants with Immunogenic response (via the frequency of influenza-specific T-cells) at Week 26	16 Participants	13 Participants

Adverse Events

MVA-NP+M1 Group

Serious events: 18 serious events

Other events: 524 other events

Deaths: 0 deaths

Saline Placebo Group

Serious events: 22 serious events

Other events: 435 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Tom Evans, MD

Vaccitech Ltd.

Phone: +44 01865 591 445

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60