A Randomised, Double-blind, Placebo-controlled Phase IIb Trial to Test FLU-v Vaccine
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: FLU-v; adjuvanted FLU-v; Saline; Adjuvanted placebo
Intervention description: Subcutaneous injection in the upper arm with 500 ug of FLU-v as 0.5ml suspension in 0.01M HCl and 0.01M NaOH; Subcutaneous injection in the upper arm with 500ug of FLU-v emulsified in 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection; Subcutaneous injection in the upper arm with 0.5ml of saline; Subcutaneous injection in the upper arm with an emulsion made with 0.25ml of Montanide ISA-51 adjuvant (Seppic, France) and 0.25ml of water for injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 175.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: broad; universal; vaccine; influenza; peptide; Tcell; UNISEC

Summary:

      FLU-v is a vaccine that aims to protect against a wide range of flu viruses. The purpose of
      this study is to measure the immune responses induced by FLU-v vaccine. This study will look
      at how safe FLU-v is when administered and how successful it is in preventing flu or reducing
      the severity of the flu symptoms.

      The study requires 222 healthy volunteers 18-60 years old. Participation in the study will
      take a maximum of 7 months and consists of 5 visits. During visit 1, subjects will be
      examined by a doctor to make sure they are eligible to enter the study. A 15ml blood sample
      (a tablespoon) will be taken to check general health followed by a general physical exam.
      Medical history and some personal information will be collected. Subjects that have received
      the traditional flu vaccine in the past 6 months, and those females who are pregnant or
      breastfeeding will not be allowed in the study. Subjects of childbearing age must agree to
      use effective contraceptive methods.

      At visit 2, subjects will be randomly allocated to one of the four treatment groups
      summarised below:

        -  Treatment 1: FLU-v (test vaccine) at the start of the study (Day 0) and then again 21
           days later

        -  Treatment 2: FLU-v (test vaccine) with an additional substance added [known as Montanide
           ISA 51] which improves the effect of the test vaccine. Injection will be given on Day 0
           and then Placebo (no test vaccine) alone 21 days later

        -  Treatment 3: Placebo (no test vaccine) injection on Day 0 and then 21 days later

        -  Treatment 4: Placebo (no test vaccine) with an additional substance added [known as
           Montanide ISA 51] on Day 0 and then Placebo (no test vaccine) alone 21 days later
           Treatment will be injected under the skin in the upper arm on day 0 (visit 2) and 21
           days later (visit 3). Blood samples will be taken before treatment (day 0), and on days
           42 (visit 4) and 180 (visit 5) to the immune responses induced by the vaccine.

      Subjects will be asked to complete a diary card to write down any side effects that they may
      experience after vaccination. Subjects will also be asked to complete another diary card to
      document any flu-like symptoms experienced between December 2016 and March 2017, this time is
      officially considered as the flu season. During this period, if the subject experiences
      flu-like symptoms, a collection of a nose and tonsil swab will be arranged by the study site
      to confirm whether they have the flu or not.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy males or healthy non-pregnant females (as indicated by a negative blood
             pregnancy test done during the screening visit) between the ages of 18 and 60 years,
             inclusive;

          -  Women of childbearing potential (not surgically sterile or postmenopausal for greater
             than or equal to one year) and men must agree to practice appropriate contraception (a
             combination of barrier and hormonal methods for women and a condom for men) from
             screening and until at least 30 days (up to Study Day 51 for females) and 90 days (up
             to Study Day 111 for males), after the last vaccination.

          -  A subject is in good health, as determined by a comprehensive clinical assessment
             {vital signs (heart rate, blood pressure, oral temperature)}, blood chemistry test
             (electrolytes, renal/kidney function, liver function, C-reactive protein, complete
             blood count), medical history, general physical examination, self-reported illness}
             and the clinical judgment of the investigator;

          -  Able to understand and comply with planned study procedures;

          -  Provides signed informed consent form

        Exclusion Criteria:

          -  Has a known allergy to any of the components of the vaccine.

          -  Has a history of severe reaction following immunization.

          -  Persons with immune deficiency/disorder, whether due to genetic defect,
             immunodeficiency disease, or immunosuppressive therapy.

          -  Women who have a positive pregnancy test during the screening visit or who are
             breastfeeding.

          -  Has a history of any of the following (reported by subjects):

               -  Acute disseminated encephalomyelitis (ADEM);

               -  Neoplastic disease - current or previous;

               -  Asthma or severe allergic disease;

               -  Bleeding disorders

               -  Chronic Hepatitis B and/or C infection;

               -  Chronic liver disease;

               -  Diabetes mellitus;

               -  Guillain-Barré syndrome;

               -  HIV;

               -  Rheumatoid arthritis or other autoimmune diseases;

               -  Severe renal disease;

               -  Transplant recipients;

               -  Unstable or progressive neurological disorders.

          -  Receipt of medicines/treatments that may affect evaluation of immunogenicity such as:

               -  Oral or parenteral steroids, high-dose inhaled steroids (greater than 800
                  micrograms/day of beclomethasone dipropionate or equivalent) or other
                  immunosuppressive or cytotoxic drugs (azathioprine (Imuran), cyclosporine
                  (Neoral, Sandimmune, SangCya); monoclonal antibodies such as basiliximab
                  (Simulect), daclizumab (Zinbryta), infliximab (Remicade), rituximab (MabThera),
                  alemtuzumab (Campath and Lemtrada), omalizumab (Xolair), abatacept (Orencia),
                  adalimumab (Humira and Exemptia) and etanercept (Enbrel)basiliximab (Simulect),
                  daclizumab (Zenapax), and muromonab (Orthoclone OKT3); corticosteroids such as
                  prednisone (Deltasone, Orasone); tacrolimus (Prograf, Advagraf, Protopic);
                  Glatiramer acetate (Copaxone); Mycopehnolate (Cellcept); Sirolimus (Rapamune);
                  (within 6 months of vaccination in this study)

               -  Immunoglobulin or other blood products (plasma, blood cells, coagulation factors,
                  haemoglobin)(within 3 months of vaccination in this study);

               -  An experimental agent (vaccine, drug, biologic, device, blood product, or
                  medication) within 1 month of vaccination in this study, or expects to receive an
                  experimental agent (during the study period).

               -  Influenza antiviral medication (Amantadine (Symmetrel); Rimantadine (Flumadine);
                  Zanamivir (Relenza), Oseltamivir (Tamiflu) (within 4 weeks of vaccination in this
                  study).

          -  Has received any influenza vaccine within 6 months of vaccination in this study.

          -  Has influenza-like illness (a sudden onset of symptoms and at least one of the four
             systemic symptoms-fever or feverishness, malaise, headache, myalgia and at least one
             of the three respiratory symptoms-cough, sore throat, shortness of breath) or acute
             respiratory infection (a sudden onset of symptoms and at least one of the four
             respiratory symptoms-cough, sore throat, shortness of breath, coryza (Rhinitis) and a
             clinician's judgement that the illness is due to an infection) within 6 months prior
             to vaccination in this study. These symptoms must have stopped the subject from
             carrying out their normal daily activities such as attending work or school for a
             period of at least 3 days.

          -  Has an acute illness, including an oral temperature greater than 38 degrees Celsius,
             within 1 week of vaccination.

          -  Has a history of alcohol or drug abuse within the last 2 years deemed unsuitable for
             inclusion by the investigator.

          -  Any abnormal haematology values and/or serum chemistries judged by the Investigator as
             clinically significant.