Evaluation of Safety, Immunogenicity, and Prevention of TB With AERAS-404 and BCG Revaccination in Healthy Adolescents
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety,
      Immunogenicity, and Prevention of Infection with Mycobacterium tuberculosis of AERAS-404 and
      BCG Revaccination in Healthy Adolescents
    

Detailed description: 
      This Phase II, randomized, 3-arm, placebo controlled, partially blinded, clinical trial will
      be conducted in 990 healthy, HIV-uninfected, QFT-GIT negative, previously BCG vaccinated
      adolescents. The trial will be conducted at the South African Tuberculosis Vaccine Initiative
      (SATVI) site in the Western Cape region of South Africa, where epidemiological studies
      involving thousands of adolescents have been conducted over the last decade to characterize
      rates of Mtb infection and active TB disease in this age group. Subjects will be enrolled in
      two sequential cohorts and within each cohort subjects will be randomized in a 1:1:1 ratio to
      receive either AERAS-404 or saline placebo on Days 0 and 56, or BCG Vaccine SSI on Day 0. The
      first 90 subjects (30 from each arm) will form the Safety & Immunogenicity Cohort and will be
      subject to more intensive collection of safety data, with data reviewed by the Data
      Monitoring Committee (DMC), principal investigator and local medical monitor. Selected
      immunogenicity assays, including whole blood intracellular cytokine staining (ICS), will also
      be performed in this cohort. The remaining 900 subjects will be enrolled into the Correlates
      Cohort. All 990 subjects in the study will be evaluated for safety and biomarker outcomes,
      and for prevention of Mtb infection.

      The primary Mtb infection endpoint will be QFT-GIT conversion from a negative to positive
      test, using the manufacturer's recommended threshold of 0.35 IU/mL, at any time-point after
      Day 84 and through end of follow-up for the primary endpoint. The 84-day 'wash-out' period is
      stipulated in order to exclude subjects who may have already been Mtb infected, but not yet
      converted their QFT-GIT test at screening, thus subjects who convert their QFT-GIT at Day 84
      will not be included in the analyses of prevention of Mtb infection.
    

Intervention name(s): AERAS-404; Placebo; Bacillus Calmette-Guérin (BCG)
Intervention type(s): Biological; Drug; Biological
Intervention description(s): The H4 antigen is a fusion protein created from two Mtb antigens: antigen Ag85B and TB10.4. Ag85B is also referred to as α-antigen and is a 30-kDa mycolyl transferase protein. TB10.4 is one of three members of the very similar ESAT-6 group of proteins found in Mtb culture supernatants. TB10.4 induces broad immune responses in T cells isolated from TB subjects compared to BCG-vaccinated donors and unvaccinated donors. IC31 is a combination of a leucine-rich peptide named KLK & a synthetic oligonucleotide named ODN1a. The optimal molar ratio of KLK to ODN1a in mice is 25:1. AERAS-404 & saline placebo trial arms will be double-blinded since BCG causes a recognizable local injection site reaction, the BCG revaccination trial arm will be unblinded.; Saline; BCG SSI Vaccine is registered in South Africa for prevention of TB in children and adults. BCG, an attenuated, live culture of the Bacillus Calmette-Guérin, was originally attenuated between 1906 and 1919 by serial passage of an M. bovis strain. The manufacturer Statens Serum Institut (SSI) in Copenhagen, Denmark derives this vaccine from the Danish BCG strain 1331. BCG SSI is supplied by the manufacturer in amber 10-dose vials containing 0.75 mg lyophilized SSI BCG. The BCG revaccination trial arm will be unblinded (open label).
Other intervention name(s): H4; H4:IC31; 0.9% Saline; BCG; BCG SSI
Intervention MeSH terms: BCG Vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: BCG Vaccinated