Improved Novel VaccIne CombinaTion InflUenza Study (INVICTUS)

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

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.

Study Overview

• Status: Terminated
• Conditions: Influenza
• Intervention / Treatment: Drug: Seasonal influenza vaccine; Drug: MVA-NP+M1; Drug: Sodium chloride

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.

• Study Type: Interventional
• Enrollment (Actual): 862
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Berkshire
    • Pangbourne, Berkshire, United Kingdom, RG8 7DF
      • The Boathouse Surgery
    • Wokingham, Berkshire, United Kingdom, RG40 1XS
      • Wokingham Medical Centre
  • Oxfordshire
    • Bicester, Oxfordshire, United Kingdom, OX26 6AT
      • Bicester Health Centre
    • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
      • Centre for Clinical Vaccinology and Tropical Medicine (CCVTM
    • Witney, Oxfordshire, United Kingdom, OX28 6JS
      • Windrush Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Seasonal influenza & MVA-NP+M1; Two vaccinations will be administered: Seasonal influenza vaccine & MVA-NP+M1	Drug: Seasonal influenza vaccine; Seasonal influenza vaccine; Other Names: Quadrivalent Influenza Vaccine; Drug: MVA-NP+M1; Trial vaccine
Placebo Comparator: Seasonal influenza & saline placebo; Two vaccinations will be administered: Seasonal influenza vaccine & sodium chloride	Drug: Seasonal influenza vaccine; Seasonal influenza vaccine; Other Names: Quadrivalent Influenza Vaccine; Drug: Sodium chloride; Saline placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days with moderate or severe influenza-like symptoms	Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries	6-7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of influenza-like-illness	Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries	6-7 months
Severity of influenza-like symptoms	Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries	6-7 months
Duration of influenza-like-illnes	Throughout the influenza season, self-reported symptoms recorded using electronic or paper diaries	6-7 months
Occurrence of GP consultations from respiratory illness	Throughout the influenza season - self-reported and Medical Records	6-7 months
Occurrence of hospitalisations and deaths due to respiratory illness	Throughout the influenza season - self-reported and Medical Records	6-7 months
Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination	Self-reported symptoms recorded using electronic or paper diaries	Day 0-7
Occurrence of serious adverse events during the whole study duration	Telephone calls on Day 1-3, day 7-9 and every 3-4 weeks throughout volunteers' participation in the trial	6-7 months
Occurrence of unsolicited adverse events for 28 days following vaccination	Self-reported symptoms recorded using electronic or paper diaries	Day 0-28
Frequency of influenza-specific T-cells measured by IFNg ELISpot	To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above	6-7 months
Geometric mean titre of influenza-specific neutralising antibodies	To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above	6-7 months
Breadth of influenza-specific T-cells and antibodies	To assess the immunogenicity of MVA-NP+M1 in combination with the recommended licensed inactivated influenza vaccine in adults aged 65 years and above	6-7 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated frequency of influenza infection using historical data on the proportion of ILIs that is caused by influenza virus infection.	To explore novel clinical endpoints for future Phase III efficacy trials of influenza vaccines	6-7 months

Collaborators and Investigators

• Sponsor: Vaccitech (UK) Limited
• Collaborators: University of Oxford
• Investigators: Principal Investigator: Christopher Butler, University of Sussex

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2017
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (Actual): October 3, 2017

Study Record Updates

• Last Update Posted (Actual): November 23, 2018
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: FLU007 INVICTUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No