A Phase I Study of the Safety and Immunogenicity of a Recombinant MVA Vaccine Encoding a Secreted Antigen From M. Tuberculosis, Antigen 85A, Delivered Intradermally by a Needle Injection in Healthy Volunteers Who Have Previously Received BCG
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I study to examine the safety and immunogenicity of MVA85A delivered
      intradermally into the deltoid region in volunteers who have recieved BCG in the past 20
      years.
    

Detailed description: 
      This is a phase I study to examine the safety and immunogenicity of MVA85A delivered
      intradermally into the deltoid region in volunteers who have recieved BCG in the past 20
      years

      1. Selection of volunteers

      Volunteers for the study will be recruited through advertisements. Each volunteer will have
      received an information sheet concerning the study and will have agreed to participate in
      writing. Volunteers will be given at least 48 hours between reading the information leaflet
      and agreeing to participate. Female volunteers will be told of the theoretical risk of
      congenital anomaly should they become pregnant during the study and only those who undertake
      to take precautions to avoid pregnancy during the study period will be eligible. Volunteers
      will give signed consent for their GP's to be notified about their participation in the
      trial. The GP will be faxed a letter on the day of screening and asked to reply if they know
      of a reason why the volunteer should not take part. The signed consent form will also be
      faxed with the letter.

      2 Screening

      Volunteers will be asked to sign the informed consent form for screening. The following will
      be performed:

        -  Medical history and examination

        -  Laboratory evaluations - including clinical chemistry, haematology, HLA typing,
           anti-vaccinia antibodies, anti-HBV antibodies, anti-HCV antibodies, anti-HIV antibodies

        -  Heaf test - to exclude prior exposure to TB

        -  Urinalysis and urine pregnancy test if female

           3 Inclusion Criteria

        -  Healthy adult aged 18-55 years.

        -  Normal medical history and physical examination.

        -  Normal urine dipstick, blood count, liver enzymes, and creatinine.

           4 Exclusion Criteria

             1. Exposure to TB at any point. Previous residence in a TB endemic area.

             2. Clinically significant history of skin disorder (eczema, psoriasis, etc.), allergy,
                immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder,
                liver disease, renal disease, gastrointestinal disease, neurological illness,
                psychiatric disorder, drug or alcohol abuse.

             3. Oral or systemic steroid medication or the use of immunosuppressive agents.

             4. Positive HIV antibody test, HCV antibody test or positive HBV serology except
                post-vaccination.

             5. Heaf test greater than Grade II

             6. Confirmed pregnancy

             7. Previous MVA immunisations

                5 Withdrawal Criteria

             1. Withdrawal of consent by subject for any reason

             2. Loss to follow-up

             3. Non-compliance with study procedures

             4. Protocol violation

             5. Serious adverse event (as defined in Appendix 3)

             6. Any other reason at discretion of the Principal Investigator

             7. Confirmed pregnancy during study period

                6 Immunisation

                On Day 0, subjects will receive a single intradermal injection of 5 x 107pfu in
                0.1ml over the deltoid muscle. Subjects will be observed for an hour after all
                immunisations. Vital signs will be monitored at 30 and 60 minutes
                post-immunisation. Local reactions at the site of administration will be evaluated
                at 60 minutes.

                A photograph of the injection site may be taken at 48 hours (with written consent).
                The injection site will be reviewed 7 days after each immunization.

                Blood will be taken at the following time points: At the screening visit*, prior to
                the first vaccination, *1 week after the first vaccination, 2 weeks, 4 weeks, 8
                weeks, *12 weeks, and 24 weeks after the vaccination. Up to 55 mls will be taken at
                any one time with the total being no more than 500 mls over the study period.
                *Samples taken on these dates will be tested for full blood count and biochemical
                screen. Immunological assays will be performed at all time points to determine
                vaccine immunogenicity. A pregnancy test will be performed prior to vaccination for
                female volunteers. Peripheral blood mononuclear cells will be prepared for cellular
                immunological assays to be performed without or following cryopreservation. Other
                serological measures of immune response, i.e. antibody titres, will be assayed on
                frozen plasma samples.

                All blood tests will be taken within 1-3 days of the due date as described in the
                schedule above.

                7 Endpoints

                The occurance and severity of local side-effects The occurance and severity of
                systemic side-effects The induction of T cell responses (as measured by an
                interferon-gamma Elispot assay).

                Proliferation assays and cytotoxic T cell assays will be performed on strong CD4+
                and CD8+ responses respectively.
    

Intervention name(s): MVA85A
Intervention type(s): Biological
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Mycobacterium tuberculosis; 85A antigen; Recombinant Modified Vaccinia Ankara; Phase I study; Immunogenicity; BCG