Clinical trial NCT03300362: Improved Novel VaccIne CombinaTion InflUenza Study
Official title: A Phase IIb Study to Determine the Safety and Efficacy of Candidate INfluenza Vaccine MVA-NP+M1 in Combination With Licensed InaCTivated inflUenza Vaccine in adultS Aged 65 Years and Above
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Influenza
Lead sponsor: Barinthus Biotherapeutics
Sponsor class: INDUSTRY
Collaborators: name: University of Oxford
First posted: 2017-10-03
Enrollment: 862
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of days with moderate or severe influenza-like symptoms
timeFrame: 6-7 months
Secondary outcomes:
measure: Incidence of influenza-like-illness
timeFrame: 6-7 months
measure: Severity of influenza-like symptoms
timeFrame: 6-7 months
measure: Duration of influenza-like-illnes
timeFrame: 6-7 months
measure: Occurrence of GP consultations from respiratory illness
timeFrame: 6-7 months
measure: Occurrence of hospitalisations and deaths due to respiratory illness
timeFrame: 6-7 months
measure: Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination
timeFrame: Day 0-7
measure: Occurrence of serious adverse events during the whole study duration
timeFrame: 6-7 months
measure: Occurrence of unsolicited adverse events for 28 days following vaccination
timeFrame: Day 0-28
measure: Frequency of influenza-specific T-cells measured by IFNg ELISpot
timeFrame: 6-7 months
measure: Geometric mean titre of influenza-specific neutralising antibodies
timeFrame: 6-7 months
measure: Breadth of influenza-specific T-cells and antibodies
timeFrame: 6-7 months
Other outcomes:
measure: Estimated frequency of influenza infection using historical data on the proportion of ILIs that is caused by influenza virus infection.
timeFrame: 6-7 months
Locations:
city: Pangbourne
country: United Kingdom
facility: The Boathouse Surgery
state: Berkshire
city: Wokingham
country: United Kingdom
facility: Wokingham Medical Centre
state: Berkshire
city: Bicester
country: United Kingdom
facility: Bicester Health Centre
state: Oxfordshire
city: Oxford
country: United Kingdom
facility: Centre for Clinical Vaccinology and Tropical Medicine (CCVTM
state: Oxfordshire
city: Witney
country: United Kingdom
facility: Windrush Health Centre
state: Oxfordshire
Study officials:
affiliation: University of Sussex
name: Christopher Butler
role: PRINCIPAL_INVESTIGATOR
References:
citation: Swayze H, Allen J, Folegatti P, Yu LM, Gilbert S, Hill A, Ellis C, Butler CC. A phase IIb study to determine the safety and efficacy of candidate INfluenza Vaccine MVA-NP+M1 in combination with licensed Ina CTivated infl Uenza vaccine in adult S aged 65 years and above (INVICTUS): a study protocol. F1000Res. 2019 May 23;8:719. doi: 10.12688/f1000research.19090.1. eCollection 2019.