Table 3. Objectives, outcome measures and time-points.

Objectives	Outcome Measures	Timepoint(s) of evaluation and data collection method for this outcome measure (if applicable)
Primary Objective To assess the efficacy of MVA-NP+M1 in combination with licensed inactivated influenza vaccine in adults ≥65 years.	Primary endpoint: 1.  Number of days with moderate or severe influenza-like symptoms	Throughout the influenza season - Self-reported symptoms recorded using electronic or paper diaries
Secondary Objectives To assess the incidence of ILI in adults aged 65 years and above vaccinated with MVA-NP+M1 or Placebo in combination with the recommended annual licensed inactivated vaccine.	1.  Incidence of influenza-like-illness	Throughout the influenza season - Self-reported symptoms recorded using electronic or paper diaries
To assess the severity of influenza-like symptoms in adults aged 65 years and above vaccinated with MVA-NP+M1 or Placebo in combination with the recommended annual licensed inactivated vaccine	2.  Severity of influenza-like symptoms	Throughout the influenza season - Self-reported symptoms recorded using electronic or paper diaries
To assess the duration of ILI in adults aged 65 years and above vaccinated with MVA-NP+M1 or Placebo in combination with the recommended annual licensed inactivated vaccine	3.  Duration of influenza-like-illness	Throughout the influenza season - Self-reported symptoms will be recorded using electronic or paper diaries
To assess the occurrence of GP consultations from respiratory illness in adults aged 65 years and above vaccinated with MVA-NP+M1 or Placebo in combination with the recommended annual licensed inactivated vaccine	4.  Occurrence of GP consultations from respiratory illness	Throughout the influenza season - Self-reported and Medical Records
To assess the hospitalisations and deaths due to respiratory illness in adults aged 65 years and above vaccinated with MVA-NP+M1 or Placebo in combination with the recommended annual licensed inactivated vaccine	5.  Occurrence of hospitalisations and deaths due to respiratory illness	Throughout the influenza season - Self-reported and Medical Records
To assess the safety and reactogenicity of MVA-NP+M1 in combination with licensed inactivated influenza vaccine in adults ≥65 years. To assess the immunogenicity of MVA-NP+M1 or Placebo in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above To assess the presence of the influenza virus using virological markers, in adults aged 65 years and above vaccinated with MVA- NP+M1 or Placebo in combination with the recommended annual licensed inactivated vaccine	6.  Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 7.  Occurrence of unsolicited adverse events for 28 days following vaccination 8.  Occurrence of serious adverse events throughout participants’ participation in the trial - Frequency of influenza-specific T-cells measured by IFN-γ ELISpot - Geometric mean titre of influenza-specific neutralising antibodies - Breadth of influenza-specific T-cells and antibodies 1.  Incidence rate of laboratory confirmed influenza using RT-PCR.	Day 0–7 - Self-reported symptoms recorded using electronic or paper diaries Day 0–28 - Self-reported symptoms recorded using electronic or paper diaries Telephone calls on Day 1–3, day 7–9 and every 3–4 weeks throughout participants’ participation in the trial Blood samples drawn at enrolment (before vaccinations), day 21 and at the end of the influenza season Nasal swab sample taken by participant at the time of self-reported symptoms. Nasal swabs will be taken during the first 3 days of the onset of the self-reported symptoms
Tertiary Objectives To explore novel clinical endpoints for future Phase III efficacy trials of influenza vaccines	1.  Estimated frequency of influenza infection using historical data on the proportion of ILIs that is caused by influenza virus infection.	At the end of the influenza season