Study to Assess Efficacy and Safety of M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine in Adolescents and Adults

NCT06062238 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: Gates MRI-TBV02-301
• Study Type: interventional
• Target: 20,080
• Locations: 4 countries
• Sites: 50

Brief 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. 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

Keywords

Mycobacterium tuberculosis; M72/AS01E-4 vaccine; Safety; Immunogenicity; Efficacy; Mtb; HIV; TB vaccine

Outcome Measures

Primary Outcomes (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 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.

  Up to Month 49

Secondary Outcomes (11)

• IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion

  Up to Month 49

• IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB

  Up to Month 49

• HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB

  Up to Month 49

• IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary TB (Less stringent laboratory-confirmed pulmonary TB case definition)

  Up to Month 49

• All Cohorts: Number of participants with solicited adverse events (AEs)

  Up to 7 days

Study Arms (2)

Participants receiving M72/AS01E-4

EXPERIMENTAL

Biological: M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine

Participants receiving placebo

EXPERIMENTAL

Biological: Placebo

Interventions

Placebo BIOLOGICAL

Participants will receive an intramuscular dose of normal saline (0.9 percent \[%\] sodium chloride \[NaCl\]), on Day 1 and Day 29.

Participants receiving placebo

M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine BIOLOGICAL

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 receiving M72/AS01E-4

Eligibility Criteria

• Age: 15 Years - 44 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Wellcome Trust: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Gates Medical Research Institute: lead

Study Sites (54)

2201-Gates MRI Investigational Site

Bandung, 40161, Indonesia

Location

2204-Gates MRI Investigational Site

Depok, 16424, Indonesia

Location

2202-Gates MRI Investigational Site

Jakarta, 10430, Indonesia

Location

2205-Gates MRI Investigational Site

Jakarta, 10510, Indonesia

Location

2203-Gates MRI Investigational Site

Jakarta, 13230, Indonesia

Location

1205-Gates MRI Investigational Site

Eldoret, 30100, Kenya

Location

1203-Gates MRI Investigational Site

Homa Bay, 40300, Kenya

Location

1206-Gates MRI Investigational Site

Kericho, 20200, Kenya

Location

1207-Gates MRI Investigational Site

Kilifi, 80108, Kenya

Location

1202-Gates MRI Investigational Site

Kisumu, 40100, Kenya

Location

1208-Gates MRI Investigational Site

Machakos, 90100, Kenya

Location

1204-Gates MRI Investigational Site

Mombasa, 80103, Kenya

Location

1209-Gates MRI Investigational Site

Nairobi, 00100, Kenya

Location

1201-Gates MRI Investigational Site

Nairobi, 00202, Kenya

Location

2402-Gates MRI Investigational Site

Chichiri, 30096, Malawi

Location

2401-Gates MRI Investigational Site

Lilongwe, 0149, Malawi

Location

1033-Gates MRI Investigational Site

Bloemfontein, 9301, South Africa

Location

1016-Gates MRI Investigational Site

Brits, 0250, South Africa

Location

1021-Gates MRI Investigational Site

Cape Town, 7405, South Africa

Location

1024-Gates MRI Investigational Site

Cape Town, 7505, South Africa

Location

1006-Gates MRI Investigational Site

Cape Town, 7530, South Africa

Location

1003-Gates MRI Investigational Site

Cape Town, 7700, South Africa

Location

1034-Gates MRI Investigational Site

Cape Town, 7750, South Africa

Location

1022-Gates MRI Investigational Site

Cape Town, 7784, South Africa

Location

1008-Gates MRI Investigational Site

Cape Town, 7925, South Africa

Location

1009-Gates MRI Investigational Site

Durban, 3610, South Africa

Location

1026-Gates MRI Investigational Site

Durban, 4068, South Africa

Location

1029-Gates MRI Investigational Site

Durban, 4091, South Africa

Location

1010-Gates MRI Investigational Site

East London, 5201, South Africa

Location

1028-Gates MRI Investigational Site

Johannesburg, 1401, South Africa

Location

1031-Gates MRI Investigational Site

Johannesburg, 1811, South Africa

Location

1018-Gates MRI Investigational Site

Johannesburg, 1864, South Africa

Location

1020-Gates MRI Investigational Site

Johannesburg, 2001, South Africa

Location

1007-Gates MRI Investigational Site

Johannesburg, 2193, South Africa

Location

1014-Gates MRI Investigational Site

Jouberton, 2574, South Africa

Location

1027-Gates MRI Investigational Site

Kimberley, 8301, South Africa

Location

1017-Gates MRI Investigational Site

Klerksdorp, 2570, South Africa

Location

1012-Gates MRI Investigational Site

Ladysmith, 3370, South Africa

Location

1004-Gates MRI Investigational Site

Middelburg, 1050, South Africa

Location

1002-Gates MRI Investigational Site

Mtubatuba, 3935, South Africa

Location

1001-Gates MRI Investigational Site

Paarl, 7626, South Africa

Location

1013-Gates MRI Investigational Site

Port Elizabeth, 6001, South Africa

Location

1005-Gates MRI Investigational Site

Pretoria, 0152, South Africa

Location

1019-Gates MRI Investigational Site

Rustenburg, 0299, South Africa

Location

1011-Gates MRI Investigational Site

Soweto, 1818, South Africa

Location

1015-Gates MRI Investigational Site

Soweto, 2013, South Africa

Location

1025-Gates MRI Investigational Site

Tembisa, 1632, South Africa

Location

1032-Gates MRI Investigational Site #1

Tembisa, 1632, South Africa

Location

1030-Gates MRI Investigational Site

Vereeniging, 1935, South Africa

Location

1023-Gates MRI Investigational Site

Worcester, 6850, South Africa

Location

1302-Gates MRI Investigational Site

Lusaka, 10101, Zambia

Location

1303-Gates MRI Investigational Site

Lusaka, 412, Zambia

Location

1301-Gates MRI Investigational Site

Lusaka, 50697, Zambia

Location

1304-Gates MRI Investigational Site

Ndola, 240262, Zambia

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Gates MRI

  Gates Medical Research Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 2, 2023
• Study Start: March 5, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

KE (9); ZA (34); ID (5); MA (2)