A Study to Determine the Safety and Attack Rate of the Seasonal Flu in Healthy Volunteers
A Study to Determine the Safety and Attack Rate of the Seasonal Flu in Healthy Volunteers
This is a non-controlled, open-label, single-centre, dose-escalation study to determine the
 safety, infectivity and immunology of the potential novel influenza virus H3N2 challenge
 strain. The term 'challenge agent' used in this protocol refers to the Influenza virus H3N2
 A/Belgium/4217/2015. The study utilises an adaptive study design and consists of 2 parts.
In Part 1, the primary objective is to determine the viral challenge strain dose that has an
 acceptable safety profile and an observed attack rate of >60% (i.e., at least 8 out of 12
 subjects should be infected). After Part 1, a formal interim analysis will be performed to
 select the viral challenge strain dose for Part 2 by evaluating the primary objective of Part
 1. In case no viral challenge strain dose can be selected, the study will not proceed to Part
 2.

 In Part 2, the primary objective is to determine the infectivity rate in healthy volunteers
 of the selected viral challenge strain dose for use in subsequent human challenge
 intervention studies.

 All subjects will be screened prior to viral inoculation to assess their suitability to enter
 the study. Eligible subjects will be admitted to the clinical centre for a single intranasal
 inoculation with influenza A (H3N2). In this study, up to 64 healthy subjects will receive
 the investigational challenge agent: 36 subjects in Part 1 and 18 or 28 subjects in Part 2.
Inclusion criteria:

 1. Male or female, between 18 and 55 years old (extremes included) at screening.

 2. In good physical and mental health as determined on the basis of medical history and
 general physical examination performed at screening.

 3. Absent or low levels of detectable pre-existing antibodies to influenza virus
 subtypes, including as a minimum the challenge strain, as determined by a MNT titre of
 ≤ 20 at screening.

 4. Negative urine test for selected drugs of abuse at screening and upon check-in at the
 clinical site.

 5. Negative alcohol breath test

 6. Female subjects should fulfil one of the following criteria:

 1. At least 1 year post-menopausal (amenorrhea >12 months and/or
 follicle-stimulating hormone (FSH) > 30 mIU/mL) prior to screening;

 2. Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation);

 3. Will use contraceptives as outlined in inclusion criterion 8 from screening to
 discharge.

 7. Female subjects of childbearing potential and male subjects who are sexually active
 with a female partner of childbearing potential must agree to the use of an effective
 method of birth control from screening to discharge.

 Exclusion criteria:

 1. Subjects who have received any vaccination within the last 3 months prior to screening
 or influenza vaccine within the last 12 months prior to screening or who anticipate
 receiving this during the study.

 2. Subjects with a diagnosis of influenza or influenza-like illness confirmed by a
 physician within the last 6 months prior to screening.

 3. Subjects with a positive result for adventitious agent screening (qualitative PCR
 testing) for any respiratory virus or bacteria on Day -2.

 4. Haematology and chemistry parameters, pulse rate and/or blood pressure, and ECG
 outside the reference range for the population studied and considered as clinical
 significant by the Investigator.

 5. Has an acute or chronic medical condition