TuberculosisPhase 3NCT06062238
Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults
A Phase 3 study testing M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine in people with Tuberculosis, run by Gates Medical Research Institute at 54 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 15 to 44 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20,080 participants
- Where
- 54 sitesin 5 countries
- Study dates
- 5 Mar 2024to Apr 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 44 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
- 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 return for follow-up visits).
- Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.
- 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.
- Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator.
- Negative sputum Xpert Ultra or similar assay result at screening.
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- Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, or, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.
- HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only).
- 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 antiretroviral therapy (ART) for at least 3 consecutive months at screening and agree to remain on ART throughout the trial.
- Have documented HIV Ribonucleic acid (RNA) <200 copies per milliliter (/mL) at screening.
- Have Cluster of differentiation (CD)4+ cell count ≥200 cells/microliter (μL) at screening.
- Have had Tuberculosis preventive therapy (TPT) in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators.
- Have an IGRA-positive or negative result at screening.
Who cannot join
- Current TB, or history of TB or treatment for TB disease.
- 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.
- Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol, or that will interfere with the assessments or the safety of the participant.
- Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort.
- Known bleeding disorder that is considered a contraindication to intramuscular injection or phlebotomy.
- Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day 1. These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.
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- Planned receipt of blood, or blood products during the trial period.
- Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine.
- History of previous administration of an experimental Mtb vaccine including M72/AS01E in a previous trial.
- History of allergy or hypersensitivity to the trial intervention, excipients, or related Substances.
- An indeterminate IGRA test result at screening
- Female participants with any one of the following conditions: currently pregnant or lactating; having positive serum pregnancy test during the screening window, positive urine pregnancy test on Day 1, planning a pregnancy within 2 months after completion of the vaccination series.
- Only in the HIV Cohort: Safety laboratory values at screening that are of concern, based on investigator's judgment. Note that preexisting stable chronic disease will not necessarily lead to exclusion, especially if laboratory values are graded as mild.
- Participation in an interventional clinical trial in which the participant has been or will be exposed to an investigational product (pharmaceutical product or device), within 28 days prior to signing consent or assent, or during the trial period.
- Individuals who are acting as personnel for this trial, or who have immediate family members (brother, sister, child, parent, or the spouse/partner) who are acting as personnel for this trial.
- Child in Care, defined as a child who is under the care (control or protection) of an agency, organization, institution or entity by the courts, the government body, acting in accordance with powers conferred in them by law or regulations. The definition of a child in care can include a child who is cared for by foster parents or living in a care home or institution, provided that the arrangements fall within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed LAR.
- Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1.
Trial locations and contacts
54 sites in 5 countries.
54 sites in 5 countries
South Africa34 sites
1033-Gates MRI Investigational Site
Bloemfontein, 9301
1016-Gates MRI Investigational Site
Brits, 0250
1021-Gates MRI Investigational Site
Cape Town, 7405
1024-Gates MRI Investigational Site
Cape Town, 7505
1006-Gates MRI Investigational Site
Cape Town, 7530
1003-Gates MRI Investigational Site
Cape Town, 7700
1034-Gates MRI Investigational Site
Cape Town, 7750
1022-Gates MRI Investigational Site
Cape Town, 7784
1008-Gates MRI Investigational Site
Cape Town, 7925
1009-Gates MRI Investigational Site
Durban, 3610
1026-Gates MRI Investigational Site
Durban, 4068
1029-Gates MRI Investigational Site
Durban, 4091
1010-Gates MRI Investigational Site
East London, 5201
1028-Gates MRI Investigational Site
Johannesburg, 1401
1031-Gates MRI Investigational Site
Johannesburg, 1811
1018-Gates MRI Investigational Site
Johannesburg, 1864
1020-Gates MRI Investigational Site
Johannesburg, 2001
1007-Gates MRI Investigational Site
Johannesburg, 2193
1014-Gates MRI Investigational Site
Jouberton, 2574
1027-Gates MRI Investigational Site
Kimberley, 8301
1017-Gates MRI Investigational Site
Klerksdorp, 2570
1012-Gates MRI Investigational Site
Ladysmith, 3370
1004-Gates MRI Investigational Site
Middelburg, 1050
1002-Gates MRI Investigational Site
Mtubatuba, 3935
1001-Gates MRI Investigational Site
Paarl, 7626
1013-Gates MRI Investigational Site
Port Elizabeth, 6001
1005-Gates MRI Investigational Site
Pretoria, 0152
1019-Gates MRI Investigational Site
Rustenburg, 0299
1011-Gates MRI Investigational Site
Soweto, 1818
1015-Gates MRI Investigational Site
Soweto, 2013
1025-Gates MRI Investigational Site
Tembisa, 1632
1032-Gates MRI Investigational Site #1
Tembisa, 1632
1030-Gates MRI Investigational Site
Vereeniging, 1935
1023-Gates MRI Investigational Site
Worcester, 6850
Kenya9 sites
1205-Gates MRI Investigational Site
Eldoret, 30100
1203-Gates MRI Investigational Site
Homa Bay, 40300
1206-Gates MRI Investigational Site
Kericho, 20200
1207-Gates MRI Investigational Site
Kilifi, 80108
1202-Gates MRI Investigational Site
Kisumu, 40100
1208-Gates MRI Investigational Site
Machakos, 90100
1204-Gates MRI Investigational Site
Mombasa, 80103
1209-Gates MRI Investigational Site
Nairobi, 00100
1201-Gates MRI Investigational Site
Nairobi, 00202
Indonesia5 sites
2201-Gates MRI Investigational Site
Bandung, 40161
2204-Gates MRI Investigational Site
Depok, 16424
2202-Gates MRI Investigational Site
Jakarta, 10430
2205-Gates MRI Investigational Site
Jakarta, 10510
2203-Gates MRI Investigational Site
Jakarta, 13230
Zambia4 sites
1302-Gates MRI Investigational Site
Lusaka, 10101
1303-Gates MRI Investigational Site
Lusaka, 412
1301-Gates MRI Investigational Site
Lusaka, 50697
1304-Gates MRI Investigational Site
Ndola, 240262
Malawi2 sites
2402-Gates MRI Investigational Site
Chichiri, 30096
2401-Gates MRI Investigational Site
Lilongwe, 0149
About this study
Official 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 Administered Intramuscularly on a 0,1-month Schedule to Adolescents and Adults
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.
- Conditions
- Tuberculosis
- Being tested
- M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine, Placebo
- Keywords
- Mycobacterium tuberculosis, M72/AS01E-4 vaccine, Safety, Immunogenicity, Efficacy, Mtb, HIV, TB vaccine
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M72/AS01E-4 Mycobacterium tuberculosis investigational vaccineBiological
Participants will receive an intramuscular dose of M72 (recombinant fusion protein) reconstituted with AS01E-4 (an adjuvant system), on Day 1 and Day 29.
PlaceboBiological
Participants will receive an intramuscular dose of normal saline (0.9 percent [%] sodium chloride [NaCl]), on Day 1 and Day 29.
| Study group | Role | What they receive |
|---|---|---|
| Participants receiving M72/AS01E-4 | Experimental | Not described Receives: Biological: M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine |
| Participants receiving placebo | Experimental | Not described Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Month 49
Secondary outcomes (11)
IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion
Measured: Up to Month 49
IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB
Measured: Up to Month 49
HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB
Measured: 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
Measured: Up to Month 49
All Cohorts: Number of participants with solicited adverse events (AEs)
Measured: Up to 7 days
All Cohorts: Number of participants with unsolicited AEs
Measured: Up to 28 days
All Cohorts: Number of participants with serious adverse events (SAEs)
Measured: Up to Month 13
All Cohorts: Number of participants with potential immunemediated diseases (pIMDs)
Measured: Up to Month 13
All Cohorts: Number of participants with SAEs related to trial participation
Measured: Up to Month 49
All cohorts: Number of participants with geometric mean concentration (GMC) of M72-specific antibodies
Measured: 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
Measured: At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2023
- Study start5 Mar 2024
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20,080 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gates Medical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust, Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Gates MRI, Study director, Gates Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06062238
- Sponsor's protocol ID
- Gates MRI-TBV02-301
- Status last verified
- Aug 2026
- First submitted
- 25 Sep 2023
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes