The overall objective is to establish an influenza Controlled Human Infection Model (CHIM) in Canada that can be used to assess the safety and efficacy of candidate vaccines, biologics, and therapeutics targeting influenza viruses.
Written informed consent obtained from the participant.
18-45 years of age.
Good general health status, as determined by history and physical examination conducted no longer than 30 days prior to the challenge date.
HAI antibody titer ≤1:40 against influenza A/Texas/71/2017 (H3N2).
Underlying chronic medical condition requiring ongoing follow-up and monitoring by a physician (e.g., diabetes, seizure disorder).
Underlying renal disease or disorders requiring ongoing follow-up and monitoring by a physician. In the event a participant has a minimally elevated BUN and/or Cr at screening, the participant will either be excluded or an eCRF or creatinine clearance may be conducted to determine eligibility.
Underlying coagulation disorder history. In the event a participant reports a personal history of undiagnosed prolonged bleeding and/or recurrent nosebleeds or a personal or family history of coagulation disorders, a bleeding panel (PTT, INR, fibrinogen) will be used to rule out coagulopathy.
Hypertension, angina, or prior myocardial infarction
Sequential
Intranasal inoculation of RG-A/Texas/71/2017 (H3N2) influenza in each naris on Day 1 of the study.
Biological/VaccineParticipants will be inoculated intranasally with a single dose of the A/H3N2 challenge virus or placebo
Symptomatic influenza-virus infection
Viral shedding (as determined by a detectable quantitative RT-qPCR result on at least two days and/or at least one positive culture) beginning 24 hours after challenge (Study Day 2) until Study Day 8 and a cumulative symptom score of ≥6 from daily component symptoms computed across any consecutive 5-day window starting on Study Day 2 up to Study Day 8 post-challenge using a Modified Jackson Score (MJS).
Compare rates of symptomatic influenza-virus infection across doses administered.
Rate of symptomatic influenza-virus infection at each challenge dose group administered
Establish the safety profile of a live recombinant influenza strain RG-A/Texas/71/2017 (H3N2, Clade 3C3a) following challenge in healthy adult volunteers.
Percent of unsolicited adverse events (AEs) reported from challenge to Study Day 29. Percent of solicited AEs, specifically Grade 3 or 4 adverse reactions (ARs), defined as signs and symptoms of influenza reported from challenge to Study Day 29. Percent of medically attended adverse events (MAAEs) reported from challenge to Study Day 57. Percent of serious adverse events (SAEs) reported from challenge to Study Day 85. Percent of influenza disease with serious complications (Adverse events of special interest (AESI)) reported from challenge to Study Day 29.
Assess the viral shedding
Percent of participants within a challenge dose group with detected viral shedding in NPSs post-challenge from Study Day 2 onwards using culture and/or RT-qPCR.
Assess the peak viral load
Magnitude of viral shedding post-challenge in each participant, defined as the peak viral load in NPSs from Study Day 2 onwards using RT-qPCR.
Determine optimal collection time points for biological specimens to assess mucosal and systemic cellular responses to influenza infection (in nasopharyngeal swabs (NPSs), nasal washes (NWs), serum, saliva secretions, peripheral blood) post-challenge.
Peak magnitude in unit of detection or unit of concentration (e.g., antibody titer), among all study days on which the samples are collected and tested.
Compare detection of virus by culture and by RT-qPCR.
Correlation of virus culture and virus RT-qPCR with determining positive infection status by detection of viral shedding in participants challenged with virus.
Evaluate effects of age, sex, gender, ethnicity, baseline antibody titers, and prior receipt of seasonal influenza vaccine on SII.
Correlation of age, sex, gender, ethnicity, baseline antibody titers, and prior receipt of seasonal influenza vaccine with assigning SII as the clinical outcome.
Describe serum neuraminidase inhibition (NAI) antibody responses post-challenge
Percent of participants with serological conversion defined as a minimum 4-fold rise in post-challenge NAI serum antibodies to influenza infection at Study Days 15, 29, 57, and 85 post-challenge compared to baseline.
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Dalhousie University
Lead sponsor
Canadian Center for Vaccinology
Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre
Collaborator
