Protocol Title: A Phase 3, randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01E-4 Mycobacterium tuberculosis (Mtb) vaccine when administer v1

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remainsthe leading cause of death from a single infectious agent. The BacilleCalmette-Guérin (BCG) vaccine is currently the only licensed TB vaccine;however, it offers little to no protection against pulmonary TB in adults. Theinvestigational M72/AS01E-4 vaccine, developed by GSK, has shown promisingresults in Phase 2b clinical trials. Design: This is a Phase 3, randomized, double-blind, placebo-controlled, multicenterclinical trial to evaluate the prophylactic efficacy, safety, andimmunogenicity of the investigational M72/AS01E-4 vaccine. The vaccine will beadministered intramuscularly on a 0- and 1-month schedule to adolescents andadults aged 15 to 44 years. Participants will be randomized into two groups: onereceiving M72/AS01E-4 and the other receiving a placebo (0.9% NaCl), with bothadministered intramuscularly in the deltoid muscle—preferably in thenondominant arm. The trial includes three cohorts: IGRA-positive, IGRA-negativeand People living with HIV (PLHIV) This Phase 3 trial aims to confirm previously observedefficacy in the pahse2b trail of IGRA-positive, HIV-negative individuals and togenerate safety and immunogenicity data in both IGRA-positive and IGRA-negativeparticipants, including PLHIV. ClinicalTrials.gov Identifier: NCT06062238