MedPath

Improved Novel VaccIne CombinaTion InflUenza Study

Phase 2
Terminated
Conditions
Influenza
Interventions
Registration Number
NCT03300362
Lead Sponsor
Barinthus Biotherapeutics
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
862
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Seasonal influenza & MVA-NP+M1Seasonal influenza vaccineTwo vaccinations will be administered: Seasonal influenza vaccine \& MVA-NP+M1
Seasonal influenza & MVA-NP+M1MVA-NP+M1Two vaccinations will be administered: Seasonal influenza vaccine \& MVA-NP+M1
Seasonal influenza & saline placeboSodium chlorideTwo vaccinations will be administered: Seasonal influenza vaccine \& sodium chloride
Seasonal influenza & saline placeboSeasonal influenza vaccineTwo vaccinations will be administered: Seasonal influenza vaccine \& sodium chloride
Primary Outcome Measures
NameTimeMethod
Number of days with moderate or severe influenza-like symptoms6-7 months

Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries

Secondary Outcome Measures
NameTimeMethod
Occurrence of unsolicited adverse events for 28 days following vaccinationDay 0-28

Self-reported symptoms recorded using electronic or paper diaries

Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccinationDay 0-7

Self-reported symptoms recorded using electronic or paper diaries

Occurrence of serious adverse events during the whole study duration6-7 months

Telephone calls on Day 1-3, day 7-9 and every 3-4 weeks throughout volunteers' participation in the trial

Incidence of influenza-like-illness6-7 months

Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries

Severity of influenza-like symptoms6-7 months

Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries

Occurrence of GP consultations from respiratory illness6-7 months

Throughout the influenza season - self-reported and Medical Records

Duration of influenza-like-illnes6-7 months

Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries

Occurrence of hospitalisations and deaths due to respiratory illness6-7 months

Throughout the influenza season - self-reported and Medical Records

Frequency of influenza-specific T-cells measured by IFNg ELISpot6-7 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 antibodies6-7 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 antibodies6-7 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

Trial Locations

Locations (5)

The Boathouse Surgery

🇬🇧

Pangbourne, Berkshire, United Kingdom

Wokingham Medical Centre

🇬🇧

Wokingham, Berkshire, United Kingdom

Windrush Health Centre

🇬🇧

Witney, Oxfordshire, United Kingdom

Bicester Health Centre

🇬🇧

Bicester, Oxfordshire, United Kingdom

Centre for Clinical Vaccinology and Tropical Medicine (CCVTM

🇬🇧

Oxford, Oxfordshire, United Kingdom

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