Tuberculosis
Conditions
Interventions
Mycobacteriumtuberculosis investigationalvaccine
Placebo
Sponsors
Bill and Melinda GatesMedical Research Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be 15 to 44years of age (inclusive), at the time of signing the consent or assent. 2. Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant’s parent,or legally authorized representative(LAR) will be required to sign a statement of informed consent, in addition to the minor’s signed statement of assent. 3. In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and returnfor follow-up visits). 4. Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety. 5. Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial. 6. Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator. Pre existing stable disease is defined as not requiring significant change in therapy or hospitalization for worsening disease during the 28 days before enrollment. 7.Negative sputum Xpert Ultra or similar assay result at screening (this criterion can be waived if participant is unable to produce sufficient sputum) 8. Both males and females are included.Females are included with restrictions. 9.HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only) 10. HIV Cohort only: Participants with documented HIV infection who fulfill all of the following criteria: •have reactive anti-HIV antibody at screening • have been on ARTfor at least 3 consecutive months at screening and agree to remain on ART throughout the trial •have documented HIV RNA <200copies/mL at screening • haveCD4+ cell count =200 cells/µL at screening • have had TPT in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators • have an IGRA
Exclusion criteria
Exclusion criteria: 1. Current TB, or history of TB or treatment for TB disease 2.Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain 3. Any current medical, psychiatric, occupational, or substance abuse problems 4.Any confirmed or suspectedimmunosuppressive orimmunodeficient conditionresulting from disease (e.g.,invasive, or malignant cancers),other than HIV infection in theHIV Cohort 5. Any cytotoxicdrugs or administration ofmedications known to have amajor impact on the immunesystem, as determined by theinvestigator, within 90 days priorto Day 1. 6. Planned receipt ofblood, or blood products duringthe trial period 7. Receipt orplanned receipt of any vaccine inthe period starting 28 daysbefore, and ending 28 days after,each dose of the trial vaccine 8.History of previous administrationof an experimental Mtb vaccineincluding M72/AS01E in aprevious trial 9. History of allergy or hypersensitivity to the trialintervention, excipients, orrelated substances Diagnosticassessments 10. An indeterminate IGRA test result atscreening 11. Female participants with any one of thefollowing conditions: currentlypregnant or lactating 12. Only inthe HIV Cohort: Safety laboratory values at screening that are ofconcern, based on investigator’s judgment 13. Participation in aninterventional clinical trial inwhich the participant has been orwill be exposed to an investigational product(pharmaceutical product ordevice), within 28 days prior tosigning consent or assent, orduring the trial period. 14.Individuals who are acting aspersonnel for this trial, or whohave immediate family members who are acting as personnel forthis trial 15. Child in Care,defined as a child who is underthe care (control or protection) ofan agency or organization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. 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 weightloss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain; who has at 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 visits, preferably within a 7-day time frame, before initiation of TB treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion;IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB;HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB;All Cohorts: Number of participants with solicited Adverse events (AEs);All Cohorts: Number of participants with unsolicited AEs;All Cohorts: Number of participants with serious adverse events (SAEs);All Cohorts: Number of participants with potential immunemediated diseases (pIMDs);All Cohorts: Number of participants with SAEs related to study participation;All cohorts: Number of participants with Geometric mean concentration (GMC) of M72-specificantibodies;All cohorts: Number of participants with seropositivity of M72-specific antibodies | — |
Countries
Kenya, Malawi, South Africa, Zambia
Contacts
Public ContactMichele Botha
Manager Global Site Activation
Outcome results
None listed