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

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ClinicalTrials.gov Identifier: NCT03880474
Recruitment Status : Terminated (The trial is being stopped for futility. Season 2 cancelled.)
First Posted : March 19, 2019
Results First Posted : April 26, 2021
Last Update Posted : April 26, 2021
Sponsor:
Collaborator:
Clinical Network Services (CNS) Pty Ltd
Information provided by (Responsible Party):
Vaccitech (UK) Limited

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

Condition or disease Intervention/treatment Phase
Influenza Biological: MVA-NP+M1 Drug: Saline Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2364 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 2b Study to Determine the Efficacy of Candidate Influenza Vaccine MVA-NP+M1 in Adults Aged 18 Years and Over
Actual Study Start Date : March 18, 2019
Actual Primary Completion Date : October 15, 2019
Actual Study Completion Date : January 21, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: MVA-NP+M1
Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.)
Biological: MVA-NP+M1
Trial Vaccine

Placebo Comparator: Saline Placebo
Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%)
Drug: Saline
Sodium Chloride Placebo
Other Name: Placebo




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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) ]

    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.


  2. 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) ]

    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.


  3. 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 ]

    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.


  4. 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) ]

    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.


  5. 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) ]
    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

  6. 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 ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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:

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03880474


Locations
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Australia, New South Wales
Paratus Clinical Pty Ltd
Blacktown, New South Wales, Australia, 2148
Genesis Research Services
Broadmeadow, New South Wales, Australia, 2292
Paratus Clinical Pty Ltd
Kanwal, New South Wales, Australia, 2259
Scientia Clinical Research
Sydney, New South Wales, Australia, 2031
Australia, Queensland
University of Sunshine Coast (USC)
Morayfield, Queensland, Australia, 4506
University of Sunshine Coast (USC)
Sippy Downs, Queensland, Australia, 4556
Mater Research
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
CMAX
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Nucleus Network Pty Ltd
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Vaccitech (UK) Limited
Clinical Network Services (CNS) Pty Ltd
Investigators
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Principal Investigator: James Vandeleur, MD Paratus Clinical Pty Ltd
  Study Documents (Full-Text)

Documents provided by Vaccitech (UK) Limited:
Study Protocol  [PDF] May 20, 2019
Statistical Analysis Plan  [PDF] January 1, 2020

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Responsible Party: Vaccitech (UK) Limited
ClinicalTrials.gov Identifier: NCT03880474    
Other Study ID Numbers: FLU009
First Posted: March 19, 2019    Key Record Dates
Results First Posted: April 26, 2021
Last Update Posted: April 26, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Influenza, Human
Respiratory Tract Infections
Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases