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Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults

Primary Purpose

Influenza

Status
Terminated
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
MVA-NP+M1
Saline
Sponsored by
Vaccitech (UK) Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy male or female adults aged 18 years and over
  • Receipt of a standard-dose licensed influenza QIV vaccine on the day of, or within 28 days prior to, randomisation

  • A female participant is eligible for this study if she is not pregnant or breast feeding and one of the following:

    1. Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year)
    2. Of childbearing potential but agrees to practice effective contraception 8 weeks post-vaccination and has a negative urine pregnancy test pre-vaccination. Acceptable methods of contraception include one or more of the following:

    i. Male partner who is sterile prior to the female participant's entry into the study and is the sole sexual partner for the female participant ii. Implants of levonorgestrel iii. Injectable progestogen iv. An intrauterine device with a documented failure rate of <1% v. Oral contraceptives vi. Double barrier methods including diaphragm or condom vii. Abstinence as long as it is line with the usual and preferred lifestyle of the participant

  • Participant is willing and has capacity to provide written informed consent for participation in the study (in the Investigator's opinion)
  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Willing to allow the Investigators to discuss the participant's medical history with their healthcare provider
  • Present and able to visit the clinic in the event of an ILI episode during the influenza season

Exclusion Criteria:

  • Any other significant disease, disorder or finding (including blood test results), which, in the opinion of the Investigator, would either put the participant at risk because of participation in the study, or may influence the result of the study
  • Receipt of any investigational product within 6 months prior to study, or prior participation in a clinical study of any Influenza vaccine and agreement not to participate in another clinical study for the duration of study follow-up
  • Prior receipt of an investigational vaccine likely to impact on interpretation of the study data
  • Active infection with HIV, Hepatitis B or Hepatitis C (from patient history or medical records)
  • History of severe allergic reactions (e.g. anaphylaxis)
  • History of auto-immune disease e.g. Guillain-Barré syndrome
  • Not willing to comply with study procedures
  • Immunosuppressed or taking immunosuppressive medications
  • Use of warfarin or other blood thinning medications (aspirin is acceptable)
  • Tattoos or birthmarks at the vaccination site
  • Participant bruises easily, has haematoma or keloid scarring
  • Receipt of a licenced inactivated vaccine (e.g. pneumococcal vaccine) within 2 weeks prior to vaccination
  • Receipt of an off licensed live vaccine (e.g. herpes zoster vaccine) within 4 weeks prior to vaccination

Sites / Locations

  • Paratus Clinical Pty Ltd
  • Genesis Research Services
  • Paratus Clinical Pty Ltd
  • Scientia Clinical Research
  • University of Sunshine Coast (USC)
  • University of Sunshine Coast (USC)
  • Mater Research
  • CMAX
  • Nucleus Network Pty Ltd

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MVA-NP+M1

Saline Placebo

Arm Description

Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.)

Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%)

Outcomes

Primary Outcome Measures

Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
The measure used reverse transcription polymerase chain reaction (RT-PCR) on deep nasal/mid-turbinate swab samples to record confirmed cases of influenza. If influenza symptoms are experienced at any time during the Follow Up period, after the vaccination, participants will attend the clinic on two occasions, the first as soon as possible and at least within 72 hours of the onset of symptoms for deep nasal swabs to be taken. Both swabs must be taken within 96 hours of symptom onset. The incidence rate of laboratory confirmed influenza using RT-PCR will be estimated for each vaccine group. The 95% CI for the incidence rate will be estimated by mid-p exact method. The difference in incidence rate between vaccine groups will be compared by Fisher's exact method.

Secondary Outcome Measures

Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
ILI is defined as feeling feverish or having a fever (feeling feverish or having a fever (≥37.8Celsius)) and at least one of the following symptoms: cough, sore throat. The incidence rate of ILI by the participant completing of eDiaries will be estimated for each vaccine group. The 95% CI for the incidence will be estimated by mid-p exact method. The difference in incidence between groups will be compared by Fisher's exact method.
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs)
The solicited adverse events are commonly observed soon after receipt of vaccines and relate to local and systemic signs and symptoms. The solicited local injection site reactions (ISR) include pain, induration, warmth, and erythema (redness). The solicited systemic reactions include feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, and malaise. Participants completed eDiaries post vaccination to record ISR and systemic reactogenicity over the first 7 days post-vaccination (and the ongoing (S)AEs throughout the study). The participant reporting of all ISR categories and solicited systemic reactions was compared between the MVA-NP+M1 treated group and the Placebo treated group. Diary reported ISRs and solicited systemic reactions were summarized, by vaccination group, using descriptive statistics.
Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies)
The numbers of Immunogenic Participants (participants with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were summarized and listed. The immunogenicity here was assessed as the geometric mean titers of influenza-specific neutralizing antibodies at different timepoints in relation to the baseline, against the antigens included in the licensed QIV(Influenza A/H3N2 (HI), Influenza A/H3N2 (MN), Influenza A/H3N2 (H1N1pdm), Influenza B/Victoria, and Influenza B/Yamagata). The neutralizing antibody assays included microneutralisation and hemagglutination inhibition titers using standard methodologies for the four strains that were in the licensed vaccine. The immunogenicity analyses were conducted only on the Immunology Analysis Set of Participants.
Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
The duration of ILI is defined as the duration (days) from the first day ILI criteria met (as defined at the Secondary Outcome Measure 2) until the first day afterwards ILI criteria not met (event, ILI recovery). ILI positive participants with ILI criteria met throughout the entire influenza season were censored at the last day recorded with the ILI dairy. Survival analysis was used for the analysis of duration of ILI. The survival function for the duration of ILI was estimated by the Kaplan-Meier method.
Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC
The severity of ILI was assessed by each participant completing of electronic Diaries for symptom severity daily for the following symptoms: Feeling hot, Temperature, Cough, Sore throat, Blocked nose, Chest pain, Muscle aches, Shortness of breath with their severities (scores) recorded as: Not Present (0), Mild (1), Moderate (2), Severe (3). For each symptom, the severity score was used to calculate the area under the curve (AUC), along with the calendar day, for the entire influenza season using trapezoidal rule. Participants could be followed for varying days in the influenza season, therefore the AUC will be time weighted to 168 days: Time weighted AUC=((raw AUC [time in days])/(number of days used for analysis)) * 168
Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells)
The numbers of immunogenic Participants (with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were listed. The immunogenicity here was determined via the frequency of influenza-specific T-cells measured by IFN-γ/granzyme B ELISpot assay (enzyme linked immunospot) where the adjusted Spot Forming Units (SFU) per million PBMCs (peripheral blood mononuclear cells) after background subtraction (dimethyl sulfoxide, DMSO) were counted. The immunogenicity analyses were conducted only in the Immunology Analysis Set of Participants.

Full Information

First Posted
February 21, 2019
Last Updated
April 23, 2021
Sponsor
Vaccitech (UK) Limited
Collaborators
Clinical Network Services (CNS) Pty Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT03880474
Brief Title
Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults
Official Title
A Phase 2b Study to Determine the Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults Aged 18 Years and Over
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
The trial is being stopped for futility. Season 2 cancelled.
Study Start Date
March 18, 2019 (Actual)
Primary Completion Date
October 15, 2019 (Actual)
Study Completion Date
January 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vaccitech (UK) Limited
Collaborators
Clinical Network Services (CNS) Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A Phase 2b Study to Determine the Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults aged 18 years and over. To assess the effect of MVA-NP+M1 on the reduction of laboratory confirmed influenza when given as an adjunct to licensed quadrivalent influenza vaccine (QIV) in adults
Detailed Description
This is a Phase 2b, multicentre, randomised, single-blind study in up to 6000 adults to compare the efficacy, safety and immunogenicity of MVA-NP+M1 when given as an adjunct to a standard, licensed adult dose of QIV. The study will be conducted on an outpatient basis and will run over two consecutive influenza seasons. It is aimed to recruit 2200 participants in Season 1 and 2800-3800 participants in Season 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2364 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MVA-NP+M1
Arm Type
Experimental
Arm Description
Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.)
Arm Title
Saline Placebo
Arm Type
Placebo Comparator
Arm Description
Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%)
Intervention Type
Biological
Intervention Name(s)
MVA-NP+M1
Intervention Description
Trial Vaccine
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Placebo
Intervention Description
Sodium Chloride Placebo
Primary Outcome Measure Information:
Title
Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
Description
The measure used reverse transcription polymerase chain reaction (RT-PCR) on deep nasal/mid-turbinate swab samples to record confirmed cases of influenza. If influenza symptoms are experienced at any time during the Follow Up period, after the vaccination, participants will attend the clinic on two occasions, the first as soon as possible and at least within 72 hours of the onset of symptoms for deep nasal swabs to be taken. Both swabs must be taken within 96 hours of symptom onset. The incidence rate of laboratory confirmed influenza using RT-PCR will be estimated for each vaccine group. The 95% CI for the incidence rate will be estimated by mid-p exact method. The difference in incidence rate between vaccine groups will be compared by Fisher's exact method.
Time Frame
210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019) in line with official Australian influenza season.
Secondary Outcome Measure Information:
Title
Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
Description
ILI is defined as feeling feverish or having a fever (feeling feverish or having a fever (≥37.8Celsius)) and at least one of the following symptoms: cough, sore throat. The incidence rate of ILI by the participant completing of eDiaries will be estimated for each vaccine group. The 95% CI for the incidence will be estimated by mid-p exact method. The difference in incidence between groups will be compared by Fisher's exact method.
Time Frame
210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
Title
Number and Percentage of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms for 7 Days Following Vaccination (and Occurrence of Serious Adverse Events SAEs)
Description
The solicited adverse events are commonly observed soon after receipt of vaccines and relate to local and systemic signs and symptoms. The solicited local injection site reactions (ISR) include pain, induration, warmth, and erythema (redness). The solicited systemic reactions include feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, and malaise. Participants completed eDiaries post vaccination to record ISR and systemic reactogenicity over the first 7 days post-vaccination (and the ongoing (S)AEs throughout the study). The participant reporting of all ISR categories and solicited systemic reactions was compared between the MVA-NP+M1 treated group and the Placebo treated group. Diary reported ISRs and solicited systemic reactions were summarized, by vaccination group, using descriptive statistics.
Time Frame
7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October)
Title
Number of Participants With Immunogenic Response (Immunogenicity of MVA-NP+M1 in Adjunction With Licensed QIV as Assessed Via Titres of Influenza-specific Neutralizing Antibodies)
Description
The numbers of Immunogenic Participants (participants with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were summarized and listed. The immunogenicity here was assessed as the geometric mean titers of influenza-specific neutralizing antibodies at different timepoints in relation to the baseline, against the antigens included in the licensed QIV(Influenza A/H3N2 (HI), Influenza A/H3N2 (MN), Influenza A/H3N2 (H1N1pdm), Influenza B/Victoria, and Influenza B/Yamagata). The neutralizing antibody assays included microneutralisation and hemagglutination inhibition titers using standard methodologies for the four strains that were in the licensed vaccine. The immunogenicity analyses were conducted only on the Immunology Analysis Set of Participants.
Time Frame
Day 28 and Week 26
Title
Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
Description
The duration of ILI is defined as the duration (days) from the first day ILI criteria met (as defined at the Secondary Outcome Measure 2) until the first day afterwards ILI criteria not met (event, ILI recovery). ILI positive participants with ILI criteria met throughout the entire influenza season were censored at the last day recorded with the ILI dairy. Survival analysis was used for the analysis of duration of ILI. The survival function for the duration of ILI was estimated by the Kaplan-Meier method.
Time Frame
210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
Title
Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC
Description
The severity of ILI was assessed by each participant completing of electronic Diaries for symptom severity daily for the following symptoms: Feeling hot, Temperature, Cough, Sore throat, Blocked nose, Chest pain, Muscle aches, Shortness of breath with their severities (scores) recorded as: Not Present (0), Mild (1), Moderate (2), Severe (3). For each symptom, the severity score was used to calculate the area under the curve (AUC), along with the calendar day, for the entire influenza season using trapezoidal rule. Participants could be followed for varying days in the influenza season, therefore the AUC will be time weighted to 168 days: Time weighted AUC=((raw AUC [time in days])/(number of days used for analysis)) * 168
Time Frame
210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
Title
Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells)
Description
The numbers of immunogenic Participants (with positive immune response as assessed at Day 28 and week 26 in relation to the baseline day 0 Immunogenicity) were listed. The immunogenicity here was determined via the frequency of influenza-specific T-cells measured by IFN-γ/granzyme B ELISpot assay (enzyme linked immunospot) where the adjusted Spot Forming Units (SFU) per million PBMCs (peripheral blood mononuclear cells) after background subtraction (dimethyl sulfoxide, DMSO) were counted. The immunogenicity analyses were conducted only in the Immunology Analysis Set of Participants.
Time Frame
Day 28 and Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy male or female adults aged 18 years and over Receipt of a standard-dose licensed influenza QIV vaccine on the day of, or within 28 days prior to, randomisation A female participant is eligible for this study if she is not pregnant or breast feeding and one of the following: Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year) Of childbearing potential but agrees to practice effective contraception 8 weeks post-vaccination and has a negative urine pregnancy test pre-vaccination. Acceptable methods of contraception include one or more of the following: i. Male partner who is sterile prior to the female participant's entry into the study and is the sole sexual partner for the female participant ii. Implants of levonorgestrel iii. Injectable progestogen iv. An intrauterine device with a documented failure rate of <1% v. Oral contraceptives vi. Double barrier methods including diaphragm or condom vii. Abstinence as long as it is line with the usual and preferred lifestyle of the participant Participant is willing and has capacity to provide written informed consent for participation in the study (in the Investigator's opinion) Able and willing (in the Investigator's opinion) to comply with all study requirements Willing to allow the Investigators to discuss the participant's medical history with their healthcare provider Present and able to visit the clinic in the event of an ILI episode during the influenza season Exclusion Criteria: Any other significant disease, disorder or finding (including blood test results), which, in the opinion of the Investigator, would either put the participant at risk because of participation in the study, or may influence the result of the study Receipt of any investigational product within 6 months prior to study, or prior participation in a clinical study of any Influenza vaccine and agreement not to participate in another clinical study for the duration of study follow-up Prior receipt of an investigational vaccine likely to impact on interpretation of the study data Active infection with HIV, Hepatitis B or Hepatitis C (from patient history or medical records) History of severe allergic reactions (e.g. anaphylaxis) History of auto-immune disease e.g. Guillain-Barré syndrome Not willing to comply with study procedures Immunosuppressed or taking immunosuppressive medications Use of warfarin or other blood thinning medications (aspirin is acceptable) Tattoos or birthmarks at the vaccination site Participant bruises easily, has haematoma or keloid scarring Receipt of a licenced inactivated vaccine (e.g. pneumococcal vaccine) within 2 weeks prior to vaccination Receipt of an off licensed live vaccine (e.g. herpes zoster vaccine) within 4 weeks prior to vaccination
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Vandeleur, MD
Organizational Affiliation
Paratus Clinical Pty Ltd
Official's Role
Principal Investigator
Facility Information:
Facility Name
Paratus Clinical Pty Ltd
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Facility Name
Genesis Research Services
City
Broadmeadow
State/Province
New South Wales
ZIP/Postal Code
2292
Country
Australia
Facility Name
Paratus Clinical Pty Ltd
City
Kanwal
State/Province
New South Wales
ZIP/Postal Code
2259
Country
Australia
Facility Name
Scientia Clinical Research
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
University of Sunshine Coast (USC)
City
Morayfield
State/Province
Queensland
ZIP/Postal Code
4506
Country
Australia
Facility Name
University of Sunshine Coast (USC)
City
Sippy Downs
State/Province
Queensland
ZIP/Postal Code
4556
Country
Australia
Facility Name
Mater Research
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
CMAX
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Nucleus Network Pty Ltd
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35305317
Citation
Evans TG, Bussey L, Eagling-Vose E, Rutkowski K, Ellis C, Argent C, Griffin P, Kim J, Thackwray S, Shakib S, Doughty J, Gillies J, Wu J, Druce J, Pryor M, Gilbert S. Efficacy and safety of a universal influenza A vaccine (MVA-NP+M1) in adults when given after seasonal quadrivalent influenza vaccine immunisation (FLU009): a phase 2b, randomised, double-blind trial. Lancet Infect Dis. 2022 Jun;22(6):857-866. doi: 10.1016/S1473-3099(21)00702-7. Epub 2022 Mar 16.
Results Reference
derived

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Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults

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