Influenza
Conditions
Interventions
Volunteers will be inoculated intranasally with a dose of 1 x 10^6 50% Tissue Culture Infective Dose (TCID-50) of the RG-(A/Texas/71/2017) H3N2 influenza virus, a good manufacturing practice (GMP), re
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age 18-45 (inclusive) years;2. A total body weight =50 kg and body mass index (BMI) =18.0 and =32.0 kg/m2;3. Good health, based upon the results of medical history, physical examination, vital signs, SpO2, ECG, and laboratory profiles of both blood and urine;4. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby. Subject is willing to remain in the inpatient Isolation Unit up until 14 days after inoculation and willing to stay in self-quarantine until no longer infectious to others, based on the clinical assessment by the investigator;5. Subject is psychologically fit and able to remain in the inpatient Isolation Unit up until 14 days after inoculation, as assessed by questionnaires at screening;
Exclusion criteria
Exclusion criteria: 1. Prior inoculation with influenza virus from the same virus type (Influenza A/H3N2) as the challenge virus within the past 2 years;2. Prior participation in another controlled human infection study with a respiratory virus in the preceding 6 months taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study;3. Share household, work closely or have close contact with infants/children (<4 years of age), pregnant women, people with respiratory diseases (e.g. asthma, COPD), immune-compromised and/or clinically vulnerable (elderly) individuals for 30 days after influenza inoculation;4. An ongoing symptomatic condition for which subject has had or has ongoing medical investigations but has not yet received a diagnosis or treatment plan e.g., ongoing fatigue without a diagnosis;5. Any history of physician-diagnosed and/or objective test-confirmed asthma, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, or chronic lung condition of any aetiology.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Infection rate after inoculation with the H3N2 (A/Texas/71/2017, Clade 3C.3a) influenza virus strainSymptomatic infection rate after inoculation with the H3N2 (A/Texas/71/2017, Clade 3C.3a) influenza virus strainTotal self-reported (solicited) complaints (from baseline until Day 15) recorded via a symptom score questionnaire electronic or paper-based according to the Modified Jackson score and FluPRO questionnaire.Total symptomsPeak symptom scoreAUC of symptoms score | — |
Secondary
| Measure | Time frame |
|---|---|
| Symptoms will be separated in 3 categories: 1. Expected (solicited) symptoms that are captured in the symptom questionnaire will only be reported as adverse events when they are categorized as severe 2. The expected (solicited) symptoms that are more severe/long-lasting than expected (longer than 14 days after virus inoculation) 3. Unsolicited adverse events, reported until Day 56 post-inoculationNature, frequency, and severity of (serious) Adverse Events (AEs) / symptoms (unsolicited) for 56 days post-inoculationPercentage of subjects reporting (S)AE from challenge to 56 days post-inoculationSelf-reported nasal pain after inoculation assessed by a numeric rating scale (NRS)Clinical laboratory testsHematologyChemistryCoagulationVital signs (including blood pressure, heart rate, respiratory rate, oxygen saturation and temperature (tympanic)National Early Warning Scores (NEWS)Concomitant medicationFindings from physical examinationViral load determined by strain-specific qPCR, and if applicable viral quantitative culture by TCID50 assay (only for qPCR positive samples)Onset of viral sheddingPeak of viral titerTime-to-peak viral loadDuration of viral shedding (number of days from first to last positive RT-PCR)Area under the curve (AUC) for influenza viral load (from Day of inoculation until Day 8)Correlation of viral load and quantitative culture with symptom scoreAntibody response (influenza specific IgG and IgA, normalized for total IgG/IgA) in nasal mucosal lining fluid and serumCellular response (e.g. T-cell activation status, T-cell composition and other cells) in nasal cells collected via mid-turbinate swab and nasopharyngeal swab, and in blood (PBMCs).Antibody response in blood, including but not limited to:Serum haemagglutination inhibiting antibodies (HAI) geometric mean titers (GMTs)Serum microneutralizing (MN) antibodies GMTsProportion of subjects with serological conversion (>4-fold rise in post-inoculation serum antibodies from baseline HAI and MN) | — |
Countries
Netherlands
Contacts
Public ContactI.M.C. Visser-Kamerling
Centre for Human Drug Research
Outcome results
None listed