Characterisation of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model
Characterisation of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model
The study will characterise Influenza A/Perth/16/2009(H3N2) virus in healthy participants
 using the viral challenge model. The study includes two cohorts.

 Cohort 1: A randomised, double-blind study of 4 titres of Challenge Virus to determine the
 optimum titre.

 Cohort 2: An open-label extension arm in which all participants will receive the 'optimum'
 titre as identified from Cohort 1.
Influenza and its associated diseases are a major cause of morbidity and mortality. The
 United States Advisory Committee on Immunization Practices recommends influenza vaccination
 for everyone over 6 months of age. The failure of the flu vaccine in 2014-2015 demonstrates
 the need for a model that allows the rapid development of novel antivirals,
 universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel
 treatments. Studies using experimental influenza virus infection in human participants have
 demonstrated that adult volunteers can be infected by nasal inoculation, and experimental
 infection is safe and not associated with transmission to contacts. The experimental virus is
 manufactured in compliance with Good Manufacturing Practice for use in the Human Viral
 Challenge Model.

 The investigators chose an H3N2 influenza subtype given that this strain has the most
 substantial impact in terms of morbidity or mortality annually as described by the Centre for
 Disease Control . The investigators first subjected the virus batch to rigorous adventitious
 agent testing, then confirmed the virus to be wild-type by Sanger sequencing and finally
 determined the virus titres appropriate for human use via the established ferret model. hVIVO
 team built on its previous experience with other H3N2 and H1N1 viruses to develop this unique
 model.

 The first part of study (Cohort 1) was to determine the safety and optimal virus titre in
 healthy adult volunteers using our unique clinical quarantine facility in London, UK. After
 the first part of the study was completed, the study was amended to add an older population
 group (45-64 years old) in order to characterise the course of infection in an age group
 better representing the at-risk population.
Inclusion Criteria:

 -  In good health with no history of major medical conditions.

 -  A total body weight ≥ 50 kg and a BMI of >18.

 -  Acceptable forms of effective contraception.

 -  An informed consent document signed and dated by the subject and Investigator.

 -  Sero-suitable for Challenge Virus.

 Exclusion Criteria:

 -  Subjects who have a significant history of any tobacco use at any time (≥ total 10
 pack year history, e.g. one pack a day for 10 years).

 -  Subjects who have been pregnant within six months prior to the study, or who have a
 positive pregnancy test at any point in the study.

 -  Any history or evidence of any clinically significant medical conditions
 (cardiovascular, gastrointestinal, endocrinological, haematological, hepatic,
 immunological, metabolic, urological, neurological, psychotic, renal, and/or other
 major disease or malignancy).

 -  History or evidence of autoimmune disease or known immunodeficiency of any cause.

 -  Subjects with any history of asthma, COPD, pulmonary hypertension, reactive airway
 disease, or chronic lung condition of any aetiology.

 -  Positive human immunodeficiency virus (HIV), Hepatitis A (HAV), B (HBV), or C (HCV)
 test.

 -  Any significant abnormality altering the anatomy of the nose or nasopharynx.

 -  Any clinically significant history of epistaxis (nose bleeds).

 -  Any nasal or sinus surgery within six months of inoculation.

 -  Recurrent history of clinically significant autonomic dysfunction.

 -  Any abnormal laboratory test or ECG.

 -  Confirmed positive test for drugs of abuse.

 -  Venous access deemed inadequate for the phlebotomy and cannulation.

 -  Any known allergies to the excipients in the Challenge Virus inoculums.

 -  Health care workers who work in units with severely immuno-compromised patients.

 -  Evidence of vaccinations within the four weeks prior to Human Viral Challenge or
 intention to receive travel vaccination before the last study visit.

 -  Receipt of blood or blood products, or loss (including blood donations) of 450 mL or
 more of blood, during the 3 months prior to inoculations.

 -  Presence of significant respiratory symptoms existing on the day of challenge or
 between admission to the unit and inoculation with virus.

 -  History suggestive of respiratory infection within 14 days prior to admission to the
 unit.

 -  Use within 28 days prior to Human Viral Challenge (Day 0) of nasal steroids * Use
 within seven days of any other medication or product (prescription or
 over-the-counter), for symptoms of hay fever, rhinitis, nasal congestion or
 respiratory tract infection.

 -  Receipt of systemic: glucocorticoids, antiviral drugs, or immunoglobulins (Igs) or any
 other cytotoxic or immunosuppressive drug.

 -  Receipt of any systemic chemotherapy agent at any time.