Influenza virus Infections and Infestations
Conditions
Interventions
Current interventions as of 21/03/2025:
Approximately 280 participants will be randomised to receive one of three active treatments or a placebo via a single intramuscular injection:
1. qIRV HA
2. tIR
Sponsors
hVIVO (United Kingdom)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 21/03/2025: 1. Written informed consent signed and dated by the participant and the investigator obtained before any assessment is performed. 2. Aged between 18 and 55 years old, inclusive, on the day prior to signing the consent form. 3. Serosuitable for the challenge virus. The serology result obtained from the influenza B virus antibody assay suggests that the participant is sensitive to influenza B virus infection (i.e., they are likely to be infected following inoculation with the challenge virus). 4. In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety, as defined by medical history, physical examination (including vital signs), electrocardiogram (ECG), and routine laboratory tests as determined by the investigator. Previous inclusion criteria: 1. Written informed consent signed and dated by the participant and the investigator obtained before any assessment is performed. 2. Aged between 18 and 55 years old, inclusive, on the day prior to signing the consent form. 3. A total body weight =50 kg and body mass index (BMI) =18 kg/m2 and =35 kg/m2. 4. In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety, as defined by medical history, physical examination (including vital signs), electrocardiogram (ECG), and routine laboratory tests as determined by the investigator. 5. Participants will have a documented medical history either prior to entering the study or following medical history review with the study physician at screening. 6. The following criteria are applicable to female participants participating in the study: 6.1. Females of childbearing potential must have a negative pregnancy test prior to enrolment. 6.2. Females of non-childbearing potential: 6.2.1. Post-menopausal females defined as amenorrhea for 12 months or greater with no alternative medical cause. A high follicle-stimulating hormone (FSH) level, within appropriate post-menopausal range, may be used to confirm post-menopausal state in the absence of combined hormonal contraception or hormone replacement therapy. If there is less than 12 months of amenorrhea 2 FSH samples are required at least 4-6 weeks apart. 6.2.2. Documented status as being permanently sterile (e.g., tubal ligation, hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). 7. The following criteria apply to female and male participants: 7.1. Female participants of childbearing potential must use 1 form of highly effective contraception. Hormonal methods must be in place from at least 2 weeks prior to the first study visit. The contraception use must continue for 1 complete menstrual cycle after the date of viral challenge. Highly effective contraception is as described below: 7.1.1. Established use of hormonal methods of contraception described below (for a minimum of 2 weeks prior to first study visit). When hormonal methods of contraception are used, male partners are required to use a condom with a spermicide: 7.1.1.1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: 7.1.1.1.1. Oral 7.1.1.1.2. Intravaginal 7.1.1.1.3. Transdermal 7.1.1.2. Progestogen-only hormonal contraception associated with inhibition of ovulation: 7.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 21/03/2025: 1. History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to the first study visit. 2. Any history or evidence of any clinically significant or currently active cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, hematological, hepatic, immunological (including immunosuppression), metabolic, urological, renal, neurological, or psychiatric disease and/or other major disease that, in the opinion of the investigator, may interfere with a participant completing the study and necessary investigations. 3. Females who: 3.1. Are breastfeeding, or 3.2. Have been pregnant within 6 months prior to the study, or 3.3. Have a positive pregnancy test at any point during screening or prior to vaccination. 4. Lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction. Significant intolerance to any food or drug in the last 12 months, as assessed by the PI. 5. Venous access deemed inadequate for the phlebotomy and cannulation demands of the study. 6. Evidence of vaccinations within the 4 weeks prior to the planned date of vaccination. 6.1. Intention to receive any vaccination(s) before the last day of follow-up. (NB. No travel restrictions will apply after the Day 28 follow-up visit). 6.2. Receipt of influenza vaccine (or another IMP relating to the treatment of influenza) OR a diagnosis of influenza or influenza-like illness confirmed by a physician in the last 6 months prior to the planned date of vaccination. 7. Receipt of any immunoglobulin or monoclonal antibodies within 3 months (or 5 half-lives, whichever is greater) prior to the planned date of vaccination. 8. Use or anticipated use during the conduct of the study of concomitant medications (prescription and/or non-prescription), including vitamins or herbal and dietary supplements within the specified windows, unless in the opinion of the study physician/PI, the medication will not interfere with the study procedures or compromise participant safety. 9. Any other medical, psychiatric, social, or occupational condition and/or responsibility that, in the opinion of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or the assessment of safety (including reactogenicity) will deem the participant unsuitable for the study. Any other reason that in the opinion of the investigator raises a concern that the participant will not be able to cope with quarantine requirements. Previous exclusion criteria as of 16/01/2025: 1. History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to the first study visit. 2. Any history or evidence of any clinically significant or currently active cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, hematological, hepatic, immunological (including immunosuppression), metabolic, urological, renal, neurological, or psychiatric disease and/or other major disease that, in the opinion of the investigator, may interfere with a participant completing the study and necessary investigations. 3. Females who: 3.1. Are breastfeeding, or 3.2. Have been pregnant within 6 months prior to the study, or 3.3. Have a positive pregnancy test at any point during screening or prior to vaccination. 4. Lifetime history of anaphylaxis and/or a lifetime history of severe allergic reac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 21/03/2025: 1. Area under the viral load-time curve (VLAUC) of influenza challenge virus as determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on nasal samples collected twice daily starting from Day 1 up to planned discharge from quarantine (Day 9). 2. Peak viral load (VLPEAK) of influenza as defined by the maximum viral load determined by quantifiable qRT-PCR measurements on nasal samples collected twice daily starting from Day 1 up to planned discharge from quarantine (Day 9) 3. RT-PCR-confirmed moderately severe influenza infection, defined as: 3.1. RT-PCR-confirmed influenza infection (two quantifiable [= lower limit of quantification {LLOQ}] qRT-PCR measurements [reported on two or more independent samples over 2 days]), starting from Day 1 up to planned discharge from quarantine (Day 9), AND 3.2. Any symptoms from the symptom diary card of grade =2 at a single time point, from Day 1 up to planned discharge from quarantine (Day 9). 4. RT-PCR-confirmed febrile influenza infection, defined as: 4.1. RT-PCR-confirmed influenza infection (2 quantifiable [=LLOQ] qRT-PCR measurements [reported on 2 or more independent samples over 2 days]) starting from Day 1 up to planned discharge from quarantine (Day 9), AND 4.2. A febrile episode, as defined by a temperature of =37.9ºC starting from Day 1 up to planned discharge from quarantine (Day 9). Previous primary outcome measures: 1. Area under the viral load-time curve (VLAUC) of influenza challenge virus as determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on nasal samples collected twice daily starting from Day 1 up to planned discharge from quarantine (Day 8). 2. Peak viral load (VLPEAK) of influenza as defined by the maximum viral load determined by quantifiable qRT-PCR measurements on nasal samples collected twice daily starting from Day 1 up to planned discharge from quarantine (Day 8) 3. RT-PCR-confirmed mod | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 21/03/2025: 1. VLAUC of influenza challenge virus as determined by viral culture on nasal samples collected twice daily starting from Day 1 up to planned discharge from quarantine (Day 9). 2. VLPEAK of influenza as defined by the maximum viral load determined by quantitative viral culture measurements on nasal samples collected twice daily starting from Day 1 up to planned discharge from quarantine (Day 9). 3. Duration of quantifiable influenza, as assessed by qRT-PCR measurements in nasal samples, starting from Day 1 up to planned discharge from quarantine (Day 8). Duration is defined as the time (hours) from first quantifiable (=LLOQ) until first confirmed <LLOQ assessment after their peak measure (after which no further virus is quantified). 4. Duration of quantifiable influenza viral culture measurements in nasal samples, starting from Day 1 up to planned discharge from quarantine (Day 9). Duration is defined as the time (hours) from first quantifiable (=LLOQ) until first confirmed <LLOQ assessment after their peak measure (after which no further virus is quantified). 5. RT-PCR-confirmed influenza infection defined as two quantifiable (=LLOQ) RT-PCR measurements (reported on two or more independent samples over 2 days), starting from Day 1 up to planned discharge from quarantine (Day 9). 6. RT-PCR-confirmed symptomatic influenza infection, defined as: 6.1. RT-PCR-confirmed influenza infection (two quantifiable [=LLOQ] qRT-PCR measurements [reported on two or more independent samples over 2 days]) starting from Day 1 up to planned discharge from quarantine (Day 9), AND 6.2. Symptom score totaling =2 at a single time point, from Day 1 up to planned discharge from quarantine (Day 9). 7. Area under the curve over time of total symptoms score (TSSAUC) as measured by graded symptom scoring system collected 3 times daily starting from Day 1 up to planned discharge from quarantine (Day 9). 8. Peak daily symptom score: individual | — |
Countries
United Kingdom
Outcome results
None listed