A Phase I Study to Evaluate the Safety and Immunogenicity of PnuBioVax
Condition: Pneumococcal Infection
MeSH terms: Pneumococcal Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Streptococcus pneumoniae is a type of bacteria that can cause infections of the ears, sinuses
      or lungs. It can also cause more serious infections of the blood or brain. The elderly and
      young children are more vulnerable to these types of infections.

      The vaccines available at present are effective only on a certain number of strains of the
      bacteria. The PnuBioVax vaccine is being developed to work on a broader range of strains.
      This study will be looking at the safety and tolerability of the study drug for three
      different dosages: 50 μg, 200 μg, and 500 μg compared to placebo.

      The population eligible to take part in the study are healthy male and female subjects
      between 18 and 40 years of age.

      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. Only subjects who agree to undertake precautions to avoid
      pregnancy of either themselves of their partner during the study period will be eligible.
      Volunteers will give signed consent for their physician to be notified about their
      participation in the trial.
    

Detailed description: 
      This is a phase I study to assess the safety and immunogenicity of PnuBioVax administered on
      three occasions 28 days apart at dose levels of 50 µg, 200 µg, and 500 µg in healthy adult
      subjects.

      The study will involve 8 visits in total; screening period to determine eligibility, 3
      treatment periods comprising of an overnight stay at the clinic (days 1, 29 and 57) and 4
      outpatient follow up visits (7 days after each dosing period and one on day 85). Volunteers
      will also be requested to complete a diary card from day 1 to day 85.

      36 Volunteers will take part in this study and will be randomly assigned to each sequential
      dose group as follows:

        -  Cohort 1: up to 3 doses of 50 µg of PnuBioVax or placebo

        -  Cohort 2: up to 3 doses of 200 µg of PnuBioVax or placebo

        -  Cohort 3: up to 3 doses of 500 µg of PnuBioVax or placebo Within each cohort, nine
           subjects will receive PnuBioVax and three subjects will receive placebo. Each subject
           will receive administrations of PnuBioVax or placebo on Days 1, 29 and 57.

      The lowest dose of PnuBioVax will be evaluated first (i.e. Cohort 1). Dose escalation will
      only proceed in the subsequent cohorts if blinded safety data (adverse events, injection site
      reactions, concomitant medication, vital signs and routine laboratory assessments) from day 8
      from the 12 subjects in the preceding cohort have been reviewed by the Sponsor and Principal
      Investigator and are found to be satisfactory. The Sponsor and Principal Investigator will
      also review the safety data after each subsequent dose to ensure repeat dosing does not give
      rise to safety issues.

      Subjects will be followed up 7 days after each vaccination and also by telephone 14 and 21
      days following each vaccination. Subjects will also be requested to record any adverse events
      in a daily diary. Haematology, biochemistry and vital signs will be measured at each follow
      up visit (except day 85) and a full safety follow up will be completed 7 days after the third
      dose (day 64).

      Bloods will be drawn for evaluation of the immune response to the PnuBioVax, 28 days
      following the first, second and third administrations (Days 29, 57 and 85). The blood draw at
      day 85 will also be used for exploratory analyses.

      The presence of autoantibodies will be assessed at screening (baseline level), and day 85 by
      measurement of anti nuclear antibody (ANA) levels.
    

Intervention name(s): PnuBioVax; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): Three administrations (by intramuscular injection) given 28 days apart to 9 subjects.; Placebo administered by intramuscular injection to 3 subjects in each cohort. Three administrations given 28 days apart.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Pneumococcal Infection; Phase I; Immunogenicity; Safety; Vaccination