Influenza
Conditions
Brief summary
A Phase IIb randomised, participant-blinded, placebo-controlled, multi-centre phase IIb efficacy study in 2030 volunteers aged 65 and over. The study will assess the safety and efficacy of the co-administration of a viral vectored vaccine, MVA- NP+M1, and the annual recommended licensed inactivated influenza vaccine (IIV). Within the main cohort 100 participants will be recruited to an immunology sub-cohort.
Detailed description
The efficacy of current seasonal influenza vaccines is limited in the face of antigenic mismatch between circulating viral strains and those in the given vaccine. Additionally vaccination in older adults, a major target group for vaccination, prevents laboratory-confirmed influenza in only 30-40% compared to 70-90% in young adults. The hypothesis in this Phase IIb efficacy study is that a new vaccine MVA-NP+M1 with licensed inactivated influenza vaccine (IIV) in the older age group will be able to induce immune responses that protect individuals against influenza illness, severity of symptoms and reduce viral shedding, thereby increasing the protection conferred by seasonal influenza vaccine alone. A total of 2030 participants who are 65 years of age or over and eligible for annual seasonal influenza vaccination and provide informed consent will be recruited to the study. Potential volunteers will be mailed an invitation to take part by their GPs or recruited by local advertisements. Participants will be randomised to receive either MVA- NP+M1 with licensed IIV or saline placebo with licensed IIV. In the first 28 days after vaccination, participants will record adverse events using an electronic or paper diary. The participants will be contacted by telephone 1 day and 7 days post-vaccination to enquire about any serious adverse events and support follow up. During influenza season participants will record weekly whether or not they have had an influenza like illness (ILI). For every ILI episode experienced, the participants will record the severity of their symptoms daily. Among the participants, a total of 100 volunteers (50 in each group) will be recruited into an immunology sub-cohort. They will have blood samples collected on the day of vaccination, 1 week, 3 weeks and 26 weeks post-vaccination for monitoring of laboratory adverse events and immunogenicity purposes.
Interventions
DRUGSeasonal influenza vaccine
Seasonal influenza vaccine
DRUGMVA-NP+M1
Trial vaccine
DRUGSodium chloride
Saline placebo
Sponsors
University of Oxford
Barinthus Biotherapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Masking description
Investigators recording clinical outcomes will also be blinded
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Volunteer is willing and has capacity to provide written informed consent for participation in the trial (in the Investigator's opinion). * Male or female adults, aged 65 years and above * Able and willing (in the Investigator's opinion) to comply with all study requirements * Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner * Eligible to receive seasonal influenza vaccine
Exclusion criteria
* Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be exacerbated by any component of the vaccine (e.g. egg allergy) * Ongoing terminal illness with a life expectancy estimated to be approximately \<6 months. * Continuous use of oral anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) * Any other significant disease, disorder or finding (including blood test results), which, in the opinion of the Investigators, would either put the volunteer at risk because of participation in the study, or may influence the result of the study * Participation in another clinical trial of an investigational medicinal product in the 30 days preceding enrolment, or planned use during the study period * Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data * Receipt of annual seasonal influenza vaccine prior to enrolment (for the same influenza season volunteers are recruited in) * Not willing to comply with study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of days with moderate or severe influenza-like symptoms | 6-7 months | Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination | Day 0-7 | Self-reported symptoms recorded using electronic or paper diaries |
| Incidence of influenza-like-illness | 6-7 months | Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries |
| Severity of influenza-like symptoms | 6-7 months | Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries |
| Duration of influenza-like-illnes | 6-7 months | Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries |
| Occurrence of GP consultations from respiratory illness | 6-7 months | Throughout the influenza season - self-reported and Medical Records |
| Occurrence of hospitalisations and deaths due to respiratory illness | 6-7 months | Throughout the influenza season - self-reported and Medical Records |
| Occurrence of serious adverse events during the whole study duration | 6-7 months | Telephone calls on Day 1-3, day 7-9 and every 3-4 weeks throughout volunteers' participation in the trial |
| Occurrence of unsolicited adverse events for 28 days following vaccination | Day 0-28 | Self-reported symptoms recorded using electronic or paper diaries |
| Frequency of influenza-specific T-cells measured by IFNg ELISpot | 6-7 months | To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above |
| Geometric mean titre of influenza-specific neutralising antibodies | 6-7 months | To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above |
| Breadth of influenza-specific T-cells and antibodies | 6-7 months | To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above |
Other
| Measure | Time frame | Description |
|---|---|---|
| Estimated frequency of influenza infection using historical data on the proportion of ILIs that is caused by influenza virus infection. | 6-7 months | To explore novel clinical endpoints for future Phase III efficacy trials of influenza vaccines |
Countries
United Kingdom
Outcome results
None listed