Dose-escalation Safety and Immunogenicity Study to Compare MTBVAC to BCG in Newborns With a Safety Arm in Adults
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Randomized, controlled, double blind clinical trial in 2 stages (adult stage, infant stage).
      The first stage includes 18 HIV uninfected, QFT negative, BCG vaccinated, adult participants,
      randomized 1:1 to receive BCG Vaccine SSI or MTBVAC at equivalent dose (5x10E05 CFU/0.1mL)
      (n=9 in each group). Upon favourable safety review by the DSMB for all 18 adults up to day 28
      after study vaccination, the second stage will commence in thirty-six (36) HIV unexposed, BCG
      naïve, newborn infants, randomized 1:3 to receive BCG Vaccine SSI or MTBVAC at one of three
      different dose levels ( (n=9 in each group).
    

Detailed description: 
      Adult Stage:

      Eighteen (18) adult participants will be recruited and randomized equally into 1 of 2 study
      groups (n=9 per group): MTBVAC highest dose group (approx. 5x10E05 CFU/0.1mL) or BCG SSI
      standard human dose (approx. 5x10E05 CFU/0.1mL).

      Safety assessments will be conducted at D0, D7, D14, D28, D56, D90, and D180 post study
      vaccination. A diary card will be used to collect solicited local, regional, and systemic
      adverse event data from D0 through D14. Reactogenicity data will be collected at each study
      visit. Non-serious adverse events will be collected through D28. Serious adverse events will
      be collected during the entire study period.

      Infant Stage:

      Thirty-six (36) infant participants will be recruited, randomized and allocated into 4 groups
      of 9 participants: BCG (single dose level 2.5 x 10E05 CFU/0.05 mL); or MTBVAC at three
      different dose levels (lowest 2.5x10E03 CFU/0.05mL, middle 2.5x10E04 CFU/0.05mL, highest
      2.5x10E05 CFU/0.05mL).

      Vaccination of neonates will be staggered by cohorts on a 3 verum : 1 control basis to allow
      gradual evaluation of safety and reactogenicity, as follows:

      Cohort 1: 9 who receive the lowest MTBVAC dose level and 3 BCG control; Cohort 2: 9 who
      receive the highest MTBVAC dose level and 3 BCG control; Cohort 3: 9 who receive the highest
      MTBVAC dose level and 3 BCG control.

      All AEs and biochemical and haematological parameters (safety data) collected up until Day 28
      after vaccination of the last subject of each cohort will be reviewed by DSMB to authorize
      progression to the next group. Safety assessments will be conducted at D0, D7, D14, D28, D70,
      D90, D180 and D360 post study vaccination. A diary card will be used to collect solicited
      local, regional, and systemic adverse event data from D0 through D14. Reactogenicity data
      will be collected at each study visit. Non-serious adverse events will be collected through
      D28. Serious adverse events will be collected during the entire study period. Unscheduled
      follow-up face-to-face visits will be performed as needed for safety and adverse event
      management.
    

Intervention name(s): MTBVAC; BCG
Intervention type(s): Biological; Biological
Intervention description(s): Live-attenuated tuberculosis vaccine; Commercially available live-attenuated tuberculosis vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention