InfluenzaPhase 2NCT03880474
Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults
A Phase 2 study testing MVA-NP+M1 and Saline in people with Influenza, run by Barinthus Biotherapeutics at 9 sites in Australia.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- MVA-NP+M1 and Saline
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,364 participants
- Where
- 9 sitesAustralia
- Study dates
- 18 Mar 2019to 21 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Australia9 sites
CMAX
Adelaide, South Australia, 5000
Paratus Clinical Pty Ltd
Blacktown, New South Wales, 2148
Genesis Research Services
Broadmeadow, New South Wales, 2292
Paratus Clinical Pty Ltd
Kanwal, New South Wales, 2259
Nucleus Network Pty Ltd
Melbourne, Victoria, 3004
University of Sunshine Coast (USC)
Morayfield, Queensland, 4506
University of Sunshine Coast (USC)
Sippy Downs, Queensland, 4556
Mater Research
South Brisbane, Queensland, 4101
Scientia Clinical Research
Sydney, New South Wales, 2031
About this study
Official title: A Phase 2b Study to Determine the Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults Aged 18 Years and Over
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
Read the 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.
- Conditions
- Influenza
- Being tested
- MVA-NP+M1, Saline
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MVA-NP+M1Biological
Trial Vaccine
SalineDrug
Also called Placebo
Sodium Chloride Placebo
| Study group | Role | What they receive |
|---|---|---|
| MVA-NP+M1 | Experimental | Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.) Receives: Biological: MVA-NP+M1 |
| Saline Placebo | Placebo comparator | Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%) Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (6)
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.
Measured: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
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.
Measured: 7 days to a total of 210 days for SAEs (over the duration of the influenza season, between 01 May and 15 October)
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.
Measured: Day 28 and Week 26
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.
Measured: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
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
Measured: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
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.
Measured: Day 28 and Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start18 Mar 2019
- Primary completion15 Oct 2019
- Study completion21 Jan 2020
Why it stopped: The trial is being stopped for futility. Season 2 cancelled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,364 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barinthus Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinical Network Services (CNS) Pty Ltd
- Responsible party
- Sponsor
- Investigators
- James Vandeleur, MD, Principal investigator, Paratus Clinical Pty Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03880474
- Sponsor's protocol ID
- FLU009
- Status last verified
- Apr 2021
- First submitted
- 21 Feb 2019
- Last updated
- 26 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35305317
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b Study to Determine the Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults Aged 18 Years and Over
- ClinicalTrials.gov ID
- NCT03880474
- Acronym / sponsor ID
- FLU009
- Conditions
- Influenza
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial is being stopped for futility. Season 2 cancelled.
- Enrolment
- 2,364 participants (actual)
- Lead sponsor
- Barinthus BiotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Clinical Network Services (CNS) Pty Ltd
- Study start
- 18 Mar 2019 (actual)
- Primary completion
- 15 Oct 2019 (actual)
- Study completion
- 21 Jan 2020 (actual)
- First posted
- 19 Mar 2019 (actual)
- Results
- Posted 26 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MVA-NP+M1 | Experimental | Biological: MVA-NP+M1Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.) |
| Saline Placebo | Placebo comparator | Drug: SalineVaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MVA-NP+M1Trial Vaccine | Biological | MVA-NP+M1 |
| SalineAlso: PlaceboSodium Chloride Placebo | Drug | Saline Placebo |
Primary outcome
Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR).
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.
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.
6 secondary outcomes
Number and Percentage of Participants With Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
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)
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)
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)
Time frame: Day 28 and Week 26
Duration of Influenza-like Illness (ILI) as Derived From Daily ILI eDiary
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
Severity of Influenza-like Illness (ILI) Derived From Daily ILI eDiary as Time Weighted AUC
Time frame: 210 days (during the influenza season, starting on 01 May 2019 and ending on or before 15 October 2019)
Number of Participants With Immunogenic Response to MVA-NP+M1 (as Assessed Via the Frequency of Influenza-specific T-cells)
Time frame: Day 28 and Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35305317Evans 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Vandeleur, MD principal investigator
Paratus Clinical Pty Ltd
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MVA-NP+M1 and Saline in people with Influenza, run by Barinthus Biotherapeutics at 9 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and Percentage of Participants With Laboratory Confirmed Influenza Using Reverse Transcription Polymerase Chain Reaction (RT-PCR). (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03880474, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.