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
|Condition or disease||Intervention/treatment||Phase|
|Influenza||Biological: MVA-NP+M1 Drug: Saline||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2364 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
Vaccination administered: MVA-NP+M1 (IM injection, 0.5 ml, 1.5 x10^8 pfu.)
Placebo Comparator: Saline Placebo
Vaccination administered: Sodium Chloride (IM injection, 0.5 ml, 0.9%)
Sodium Chloride Placebo
Other Name: Placebo
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
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
|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|
|University of Sunshine Coast (USC)|
|Morayfield, Queensland, Australia, 4506|
|University of Sunshine Coast (USC)|
|Sippy Downs, Queensland, Australia, 4556|
|South Brisbane, Queensland, Australia, 4101|
|Australia, South Australia|
|Adelaide, South Australia, Australia, 5000|
|Nucleus Network Pty Ltd|
|Melbourne, Victoria, Australia, 3004|
|Principal Investigator:||James Vandeleur, MD||Paratus Clinical Pty Ltd|