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Human Immunodeficiency VirusPhase 2MESA-TBNCT04556981

Safety and Immunogenicity of a Mycobacterium Tuberculosis Vaccine M72/AS01E in Participants With Well-controlled HIV

A Phase 2 study testing M72/AS01E Mycobacterium tuberculosis vaccine in people with Human Immunodeficiency Virus, run by Gates Medical Research Institute at 6 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to assess the safety and immunogenicity of M72/AS01E vaccination in virally suppressed, antiretroviral-treated participants with human immunodeficiency virus infection (HIV). Read more about this study

Who is it for?
Ages 16 to 35 years
Conditions the study is for
Human Immunodeficiency Virus
What is being tested?
M72/AS01E Mycobacterium tuberculosis vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
402 participants
Where
6 sitesSouth Africa
Study dates
17 Nov 2020to 12 Aug 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 16 to 35 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participant with documented human immunodeficiency virus (HIV) infection who fulfill all of the following:
  • Has reactive anti-HIV antibody at screening
  • On antiretroviral therapy (ART) for at least 3 consecutive months at screening
  • Has documented HIV RNA <200 copies/mL at screening
  • Participants with CD4+ cell counts ≥200 cells/μL at screening
  • Participants have had tuberculosis (TB) preventive therapy (TPT) in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators
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  • Participants who are healthy as determined by medical evaluation including medical history, physical examination and laboratory tests
  • Capable of giving signed informed consent and informed assent (if appropriate), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) or informed assent form, and in the protocol.
  • Female participants of childbearing potential must agree not to become pregnant from the time of study enrollment for one year after study intervention. Women physically capable of pregnancy, sexually active and having no history of hysterectomy or tubal ligation or menopause must agree to use an effective method of avoiding pregnancy during this period.
  • Participants who agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study.

Who cannot join

  • Acute illness or fever ≥99.5°F (or ≥37.5˚C) on Day 1
  • History of active TB disease
  • Evidence of active TB disease with any of the following:
  • Have symptoms or signs of TB disease
  • Have a positive sputum Xpert MTB/RIF assay (only in participants with sputum sample at screening)
  • Are on treatment for active TB disease
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  • Evidence and/or history of clinically significant medical conditions (other than HIV infection) as judged by the investigator, including malignancies
  • 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
  • Any medications or other therapies that may impact the immune system such as immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with major organ toxicity as determined by the investigator, within 90 days prior to Day 1
  • Immunosuppressive agents including systemic steroids - prior corticosteroid therapy within 90 days prior to Day 1 (permitted: 5 mg/day prednisone equivalent, inhaled, topical, and intra-articular corticosteroids)
  • Receipt or donation of blood or blood products within 90 days prior to Day 1 or planned receipt or donation during the study period
  • Participation in an interventional clinical trial and/or receipt of any investigational drug within 180 days prior to signing informed consent or assent
  • Receipt of any vaccine in the period starting 7 days before, and ending 7 days after, each dose of the study vaccine
  • History of previous administration of experimental Mycobacterium tuberculosis vaccine
  • Safety laboratory values outside of normal range, for age and sex that are suggestive of a disease state (Grade 1 abnormalities, as per Division of AIDS [DAIDS] toxicity table version 2.1, will not lead to exclusion if the investigator considers them not clinically significant.)
  • Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
  • Current hepatitis B and/or hepatitis C infection
  • Indeterminate QFT result
  • History of allergy or hypersensitivity to the study drug, excipients or related substances
  • Shared residence with an individual who is receiving TB treatment or with someone who is known to have incompletely treated TB, e.g., Xpert MTB/RIF assay-positive, polymerase chain reaction (PCR)-positive, culture-positive, smear-positive TB, or clinically diagnosed unconfirmed TB
  • Female participants with any one of the following conditions: currently pregnant or lactating/nursing; having positive serum pregnancy test during the screening window, planning a pregnancy within 1 year after first dose of study product
  • Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel.
  • Child in Care

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

South Africa6 sites
  • Ekhaya VAC

    Cape Town, Khayelitsha, 7782

  • Desmond Tutu HIV Foundation

    Cape Town, Western Cape, 6850

  • CAPRISA

    Durban, KwaZulu-Natal, 4001

  • Wits RHI

    Johannesburg, Gauteng, 2001

  • The Aurum Institute

    Klerksdorp, North West, 2570

  • SATVI

    Worcester, Western Cape, 6850

Other trials in South Africa

About this study

Official title: A Randomized, Placebo-controlled, Observer-blind, Phase 2 Study to Evaluate Safety and Immunogenicity of the Investigational M72/AS01E Mycobacterium Tuberculosis (Mtb) Vaccine in Virally Suppressed, Antiretroviral-treated Participants With Human Immunodeficiency Virus (HIV)

The purpose of this study is to assess the safety and immunogenicity of M72/AS01E vaccination in virally suppressed, antiretroviral-treated participants with human immunodeficiency virus infection (HIV).

Being tested
M72/AS01E Mycobacterium tuberculosis vaccine, Placebo
Keywords
Mycobacterium tuberculosis, M72/AS01E Vaccine, Antiretroviral therapy, Mtb, HIV, TB vaccine
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • M72/AS01E Mycobacterium tuberculosis vaccineBiological

    Participants will receive an intramuscular dose of M72 (10 micrograms of recombinant fusion protein) reconstituted with AS01E (an adjuvant system), on Day 1 and Day 29

  • PlaceboBiological

    Participants will receive an intramuscular dose of saline (0.9% NaCl), on Day 1 and Day 29

Study groups in NCT04556981
Study groupRoleWhat they receive
M72/AS01E vaccineExperimentalNot described
Receives: Biological: M72/AS01E Mycobacterium tuberculosis vaccine
PlaceboPlacebo comparatorNot described
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.

    Measured: Day 1 through Day 7 (after first vaccination)

  2. Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.

    Measured: Day 29 through Day 35 (after second vaccination)

  3. Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after first vaccination has been presented.

    Measured: Day 1 through Day 28

  4. Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after second vaccination has been presented.

    Measured: Day 29 through Day 57

  5. Number of Participants Reporting Serious AEs (SAEs)

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of Participants reporting SAEs has been presented.

    Measured: Up to Day 390

Secondary outcomes (6)
  1. Number of Participants With Potential Immune-mediated Diseases (pIMDs)

    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. pIMDs are a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Number of Participants With Potential Immune-mediated Diseases (pIMDs) has been presented

    Measured: Up to Day 390

  2. Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline

    Blood samples were collected for the assessment of hemoglobin, leukocytes and platelets. Baseline was defined as last non-missing assessment prior to first vaccination. Laboratory grades were evaluated using the Common Terminology Criteria for AEs (CTCAE version (v)5.0) with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of Participants With Clinically Significant hematology assessments of Grade 3 and Grade 4 has been presented.

    Measured: Up to Day 390

  3. Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline

    Blood samples were collected for the assessment of Alanine Aminotransferase, Aspartate Aminotransferase and total bilirubin. Baseline was defined as last non-missing assessment prior to first vaccination. Laboratory grades were evaluated using the CTCAE v5.0 with grading as: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening or disabling. Number of Participants With Clinically Significant chemistry assessments of Grade 3 and Grade 4 has been presented.

    Measured: Up to Day 390

  4. M72-specific Antibody Titers

    Blood samples for immunogenicity evaluation of M72-specific IgG antibody in serum were collected. On Day 1 and Day 29 visits, samples were collected prior to study intervention administration. Humoral M72-specific IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA).

    Measured: Day 1, Day 29, Day 57, Day 210 and Day 390

  5. Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response

    Blood samples were analyzed for M72-specific CD4+ and CD8+ T-cell responses based on IFN-gamma and/or IL-2 expression. The CD4+ and CD8+ categories for each timepoint are mutually exclusive.

    Measured: Day 57 and Day 390

  6. Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted

    Blood samples were analyzed for M72-specific CD4+ and CD8+ T-cells exhibiting cytokine response (IFN-gamma and/or IL-2) with background subtracted. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) prior to the first study vaccination.

    Measured: At Baseline, Day 57, and Day 390

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2020
  2. Study start17 Nov 2020
  3. Primary completion12 Aug 2022
  4. Study completion12 Aug 2022

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
402 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04556981
Sponsor's protocol ID
Gates MRI-TBV02-202
Other IDs
221698/Z/20/Z
Acronym
MESA-TB
Status last verified
Jun 2025
First submitted
10 Sep 2020
Last updated
17 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Dagnew AF, Han LL, Naidoo K, Fairlie L, Innes JC, Middelkoop K, Tameris M, Wilkinson RJ, Ananworanich J, Bower D, Schlehuber L, Frahm N, Cinar A, Dunne M, Schmidt AC. Safety and immunogenicity of investigational tuberculosis vaccine M72/AS01E-4 in people living with HIV in South Africa: an observer-blinded, randomised, controlled, phase 2 trial. Lancet HIV. 2025 Aug;12(8):e546-e555. doi: 10.1016/S2352-3018(25)00124-9. Epub 2025 Jul 1.

    PubMed 40614747

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing M72/AS01E Mycobacterium tuberculosis vaccine in people with Human Immunodeficiency Virus, run by Gates Medical Research Institute at 6 sites in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention (time frame: Day 1 through Day 7 (after first vaccination)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04556981, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.

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