South African Tuberculosis Vaccine Initiative

Tuberculosis (TB) is an infection caused by bacteria passed from one person to another through the air when an infected person for instance coughs, speaks, or sneezes. This study tests the safety and vaccine-induced immune response of a new preventive TB vaccine called H107e/CAF®10b. H107e is a copy of protein parts from the bacterium causing tuberculosis, Mycobacterium tuberculosis, which are also called antigens. CAF®10b is an adjuvant which helps the body discover the antigen. The adjuvant and antigen are mixed together to formulate the final vaccine. The final formulated vaccine enhances the immune system's response against the antigen.
This is a first-in-human study, meaning this vaccine is being given to people for the first time. The primary objective is to evaluate the safety of the vaccine and its components; however, the study will also evaluate the specific immune responses generated by the new vaccine. The study is divided into two parts, phase 1a and phase 1b. Phase 1a investigates unadjuvanted H107e, CAF®10b adjuvant, H107e/CAF®10b vaccine (low adjuvant dose), and H107e/CAF®10b vaccine (full adjuvant dose). The trial products are administered twice intramuscularly. H107e is also administered intranasally in one of the groups on Day 85. Phase 1b investigates H107e/CAF®10b, H107e/CAF®10b+Bacillus Calmette-Guérin (BCG), BCG, and placebo. A placebo is a look-alike substance that contains no active drug. All groups in phase 1b receive H107e intranasally on Day 211.
A preventive TB vaccine such as H107e/CAF®10b should be able to introduce the body's immune system to antigens from Mycobacterium tuberculosis. This will result in memory in the immune system, meaning that when a person gets infected with Mycobacterium tuberculosis, the immune system will recognise and target the bacteria to prevent disease, thereby avoiding the need for antibiotic treatment and/or other treatments and their side effects.

A Phase 2a dose-defining study of MTBVAC to evaluate the safety, reactogenicity, immunogenicity, and potential for IGRA conversion and reversion, of MTBVAC in South African newborns. Ninety-nine HIV unexposed, BCG naïve newborns will be randomized to receive either BCG 2.5 x 105 CFU (n=24) or MTBVAC at one of three dose levels (n=75). Allocation will be double blind. Enrolment will be sequential into 3 cohorts of increasing MTBVAC dose (Cohort 1: n=25 MTBVAC 2.5 x 10E+04 and n=8 BCG; Cohort 2: n=25 MTBVAC 2.5 x 10E+05 and n=8 BCG; Cohort 3: n=25 MTBVAC 2.5 x 10E+06 and n=8 BCG). Dose escalation will be staggered to allow gradual evaluation of safety; final selection of the dose for Cohort 3 will be based on all available safety and immunogenicity data.

This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.
H56:IC31 (investigational vaccine)
Placebo
900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment.
5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively.
1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).