The study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01E-4 Mtb vaccine when administered intramuscularly (IM) on a 0,1-month schedule to adolescents and adults. This trial will be conducted in 3 cohorts: Interferon gamma release assay (IGRA)-positive Cohort, IGRA-Negative Cohort and Human Immunodeficiency virus (HIV) Cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20,080
Participants will receive an intramuscular dose of M72 (recombinant fusion protein) reconstituted with AS01E-4 (an adjuvant system), on Day 1 and Day 29.
Participants will receive an intramuscular dose of normal saline (0.9 percent \[%\] sodium chloride \[NaCl\]), on Day 1 and Day 29.
IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary tuberculosis (TB)
Laboratory-confirmed pulmonary TB case is defined as a participant with suspected pulmonary TB presenting with one or more of the following signs or symptoms: unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain; who has least 2 positive Mtb test results (positive Mtb culture and/or positive test result from Xpert Ultra or similar assay, excluding "trace positive"), from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment.
Time frame: Up to Month 49
IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion
Time frame: Up to Month 49
IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB
Time frame: Up to Month 49
HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB
Time frame: Up to Month 49
IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary TB (Less stringent laboratory-confirmed pulmonary TB case definition)
Laboratory-confirmed pulmonary TB case is defined as a participant with suspected pulmonary TB presenting with one or more of the following signs or symptoms: unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain; who has at least 1 positive Mtb culture or at least 1 positive result from Xpert Ultra or similar assay (excluding "trace positive"), from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment. Compose
Time frame: Up to Month 49
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2201-Gates MRI Investigational Site
Bandung, Indonesia
2204-Gates MRI Investigational Site
Depok, Indonesia
2202-Gates MRI Investigational Site
Jakarta, Indonesia
2205-Gates MRI Investigational Site
Jakarta, Indonesia
2203-Gates MRI Investigational Site
Jakarta, Indonesia
1205-Gates MRI Investigational Site
Eldoret, Kenya
1203-Gates MRI Investigational Site
Homa Bay, Kenya
1206-Gates MRI Investigational Site
Kericho, Kenya
1207-Gates MRI Investigational Site
Kilifi, Kenya
1202-Gates MRI Investigational Site
Kisumu, Kenya
...and 44 more locations
All Cohorts: Number of participants with solicited adverse events (AEs)
Time frame: Up to 7 days
All Cohorts: Number of participants with unsolicited AEs
Time frame: Up to 28 days
All Cohorts: Number of participants with serious adverse events (SAEs)
Time frame: Up to Month 13
All Cohorts: Number of participants with potential immunemediated diseases (pIMDs)
Time frame: Up to Month 13
All Cohorts: Number of participants with SAEs related to trial participation
Time frame: Up to Month 49
All cohorts: Number of participants with geometric mean concentration (GMC) of M72-specific antibodies
Time frame: At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49
All cohorts: Number of participants with seropositivity of M72-specific antibodies
Time frame: At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49