Efficacy of FLU-v in an H1N1 Influenza Human Challenge Model
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: adjuvanted FLU-v; adjuvanted placebo; Influenza challenge
Intervention description: Subcutaneous injection in the upper arm with 500mcg of FLU-v as 0.5ml emulsion in 0.25ml of WFI and 0.25ml of adjuvant Montanide ISA-51; Subcutaneous injection in the upper arm with 0.5ml emulsion made of 0.25ml of WFI and 0.25ml of adjuvant Montanide ISA-51; On day 0, administration with an intranasal sprayer of 1ml of PBS containing 10(7) TCID50 of Influenza A 2009 H1N1 human virus manufactured under GMP in certified Vero cells.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 153.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: broad; universal; vaccine; influenza; peptide; T cell; H1N1; human challenge

Summary:

      FLU-v is a broad spectrum influenza vaccine that targets regions conserved among multiple
      influenza strains. FLU-v adjuvanted with Montanide ISA-51 was shown to be safe in previous
      trials. This study aims to assess efficacy of adjuvanted FLU-v vaccine in protecting healthy
      volunteers against an influenza challenge delivered intranasally under quarantine.

      Efficacy of FLU-v will be assessed by measuring the incidence and severity of the disease in
      the treatment groups compared to the placebo group. In addition, the immune responses of the
      volunteers to FLU-v will also be explored.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment.

          2. Willingness to remain in isolation for the duration of viral shedding and to comply
             with all study requirements.

          3. The following criteria are applicable to subjects in a heterosexual relationship and
             female subjects in a same sex relationship (i.e., the criteria do not apply to male
             subjects in a same sex relationship):

               1. True abstinence- when this is in line with the preferred and usual lifestyle of
                  the subject. (Periodic abstinence [e.g. calendar, ovulation, symptothermal,
                  post-ovulation methods] and withdrawal are not acceptable methods of
                  contraception).

                  Or

               2. Two forms of effective contraceptive methods among (between) the couple, which
                  are defined as:

                    -  For males: condom with spermicidal foam/gel/film/cream, sterilisation (with
                       the appropriate post-vasectomy documentation of the absence of sperm in the
                       ejaculate. This applies only to males participating in the study).

                    -  For females:

             Women no longer of child bearing potential (post-menopausal females are defined as
             having a history of amenorrhea for at least 2 years, otherwise they should have
             documented status as being surgically sterile or post hysterectomy. The latter applies
             only to females participating in the study). If of childbearing potential, then
             acceptable forms of contraception include:

               -  Established (a minimum of 2 weeks prior to admission) use of oral, injected or
                  implanted hormonal methods of contraception.

               -  Placement of an intrauterine device (IUD) or intrauterine system (IUS).

               -  Barrier methods of contraception or occlusive cap (diaphragm or cervical/vault
                  caps), both with one of the following - spermicidal
                  foam/gel/film/cream/suppository.

                    -  The longevity of contraception is as follows:

             Males:

               -  Comply with agreed contraception at entry to quarantine, and continuing until 90
                  days after the date of viral challenge/last dosing with IMP (whichever occurs
                  last).

               -  Must not donate sperm following discharge from quarantine until 90 days after the
                  date of viral challenge/last dosing with IMP (whichever occurs last).

             Females:

             If of childbearing potential must have a negative pregnancy test at screening and just
             prior to the date of Viral Challenge, and must be using contraception consisting of
             two forms of birth control (one of which must be a barrier method) starting from at
             least 2 weeks prior to the first vaccination and continuing until 90 days after the
             date of Viral Challenge/last dosing with IMP (whichever occurs last).

          4. Willing to have samples stored for future research.

          5. Sero-suitable to the study challenge virus within 90 days of Day 0.

          6. Agrees to abstain from alcohol intake 24 hours before admission on Day -2 or Day -1
             and all other outpatient visits.

          7. Agrees to not use prescription or over-the-counter medications (including aspirin,
             decongestants, antihistamines, and other NSAIDs), and herbal medication (including,
             but not limited to, Vitamin C, Vitamin D, immune booster products, herbal tea, St.
             John's Wort), within 14 days prior to study vaccine administration through the final
             follow-up visit, unless approved by the investigator and sponsor medical monitor.

          8. An informed consent document signed and dated by the subject and the Investigator or
             delegate.

          9. A history of childhood asthma before the age of 12 years is acceptable provided the
             subject is asymptomatic without treatment. Subjects with a single episode of wheezing
             (lasting less than 2 weeks) after the age of 12 years can be included at the
             Investigator's discretion provided the episode was more than 1 year ago and did not
             require a hospital admission and/or oral/intravenous steroids.

         10. In good health with no history of major medical conditions that will interfere with
             subject safety, as defined by medical history, physical examination, and routine
             laboratory tests and determined by the Investigator at a screening evaluation.

               -  A subject with a history of Herpes type 1 or 2 infection may be included if there
                  are no active lesions present and the subject is not taking active medication.

               -  A subject with or without any evidence of atopy including any history of allergic
                  rhinitis, dermatitis, and conjunctivitis will be included as long as they do not
                  conflict with exclusion criteria. Mild to moderate arthritis of non-inflammatory
                  origin may be allowed if the subject is not at risk from relative immobility in
                  the Quarantine Unit and does not require regular medication.

         11. A documented medical history for a minimum of the last 2 years prior to inoculation.

        Exclusion Criteria:

          1. Any subjects who have smoked 10 pack years at any time. Of those subjects that have
             smoked less than 10 pack years at any time, a subject will be excluded: If regular
             smokers (e.g., smoking every day) at the time of enrolment. If current casual smoker
             or use of smoking / nicotine-related products, they must agree to refrain from smoking
             during the in-patient stay

          2. Presence of self-reported or medically documented significant medical condition
             including but not limited to:

               -  Chronic pulmonary disease (e.g., asthma (except what is stated in inclusion
                  criteria 9), COPD)

               -  Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure,
                  cardiac surgery, ischemic heart disease, known anatomic defects).

               -  Chronic medical conditions requiring close medical follow-up or hospitalisation
                  during the past 5 years (e.g., insulin dependent diabetes mellitus, renal
                  dysfunction, haemoglobinopathies).

               -  Immunosuppression, or immunodeficiency or ongoing malignancy.

               -  Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy,
                  stroke, seizures).

               -  Post infectious or post vaccine neurological sequelae.

               -  Hyperlipidemia requiring medical therapy per current American College of
                  Cardiology (ACC) and American Heart Association (AHA) guidelines published in
                  2013.

          3. Individual with body mass index (BMI) <18 and >35.

          4. Acute illness within 7 days of first vaccine administration day

          5. Clinically significant abnormal electrocardiogram (ECG) and/or parameters, as
             determined by the Investigator

          6. Subjects with clinically significant abnormal systolic and diastolic blood pressure or
             clinically significant abnormal pulse rate.

          7. Subject has abnormal pulmonary function as measured by spirometry defined as a forced
             vital capacity or forced expiratory volume in 1 second (FEV1) < 80% of predicted or
             peripheral arterial oxygen saturation (SpO2) < 92% on room air.

          8. Known allergy to treatments for influenza (including but not limited to oseltamivir,
             nonsteroidals).

          9. Known allergy to 2 or more classes of antibiotics (e.g. penicillins, cephalosporins,
             fluoroquinolones, or glycopeptides). Known allergy to excipients in the challenge
             virus inoculum

         10. Daily or household contact with vulnerable populations.

         11. Receipt of any investigational drug:

               -  within 3 months prior to the planned date of Viral Challenge/first dosing with
                  IMP (whichever occurs first).

               -  Receipt of three or more investigational drugs within the previous 12 months
                  prior to the planned date of Viral Challenge/first dosing with IMP (whichever
                  occurs first).

               -  Prior inoculation with a virus from the same virus-family as the Challenge Virus.

               -  Prior participation in another Human Viral Challenge study with a respiratory
                  virus in the preceding 12 months taken from the date of Viral Challenge/first
                  dosing with IMP (whichever occurs first) in the previous study to the date of
                  expected Viral Challenge in this study.

         12. Receipt of any vaccine within 6 months of enrolment.

         13. Self-reported or known history of alcoholism or drug abuse (including marijuana)
             within 6 months prior to enrolment, or positive urine/serum test for drugs of abuse
             during the study

         14. Self-reported or known history of psychiatric or psychological issues that require
             treatment and are deemed by the PI to be a contraindication to protocol participation.

         15. History of a previous severe allergic reaction with generalized urticaria, angioedema,
             or anaphylaxis.

         16. History or evidence of autoimmune disease or known immunodeficiency of any cause -
             with the exception of atopic dermatitis/eczema and atopic rhinitis.

         17. Subjects with any history of physician diagnosed and/or objective test confirmed
             asthma (except as per inclusion criteria 9), reactive airway disease, COPD, pulmonary
             hypertension, or chronic lung condition of any aetiology.

         18. Positive human immunodeficiency virus (HIV) within 60 days of first vaccination visit,
             active hepatitis A (HAV), B (HBV), or C (HCV) test.

         19. Any significant abnormality altering the anatomy of the nose or nasopharynx (including
             significant nasal polyps).

         20. Venous access deemed inadequate for the phlebotomy and cannulation demands of the
             study.

         21. Any nasal or sinus surgery within 6 months of Viral Challenge.

         22. Recurrent history of fainting.

         23. Those employed or immediate relatives of those employed at hVIVO or the Sponsor.

         24. Any clinically significant history of epistaxis (nosebleeds) within the last 12 months
             and/or history of being hospitalized due to epistaxis on any previous occasion.

         25. Females who:

               -  Are breastfeeding,

               -  or have been pregnant within 6 months prior to the study,

               -  or have a positive pregnancy test at any point during screening or prior to first
                  dosing with IMP.

         26. Presence of fever, defined as subject presenting with a temperature reading of >
             38.0°C on Day -43

         27. Receipt of blood or blood products, or loss (including blood donations) of 470 mL or
             more of blood during the 3 months prior to the planned date of first dosing with IMP
             or planned during the 3 months after the final visit.

         28. Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral
             drugs within 6 months prior to the planned date of first dosing with IMP.

         29. Any other finding that, in the opinion of the Investigator, deems the subject
             unsuitable for the study