Tuberculosis (TB)Phase 2NCT06272812
A Study to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living in a TB Endemic Region.
A Phase 2 study testing MTBVAC in people with Tuberculosis (TB), run by International AIDS Vaccine Initiative at 16 sites in 3 countries.
Trial summary
A Phase 2b, double-blind, randomized, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of a candidate tuberculosis (TB) vaccine, MTBVAC, against TB disease in adolescents and adults aged 14-45 years, living in a TB endemic region. Read more about this study
- Who is it for?
- Ages 14 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis (TB)
- What is being tested?
- MTBVAC
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5,500 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 19 Feb 2025to 31 Mar 2028
- Phase
- Phase 2
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 14 to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Is male or female aged 14 through 45 years on Study Day 1.
- Has completed the written (or thumb printed and witnessed) informed consent process (participants older than 18 years) or has completed the written parental consent and participant assent process (participants younger than 18 years) before any study-related procedures were performed.
- Participants who, in the opinion of the investigatory, can and will comply with the requirements of the protocol (e.g., to stay in contact with the Clinical Research Centre (CRC), return for follow-up visits)
- Has general good health as confirmed by medical history and physical examination.
- All participants born female who are engaging in sexual activity that could lead to pregnancy must commit to use an acceptable method of contraception from 21 days prior to Study Day 1 and for the 2 months after vaccination. Acceptable contraception includes:
- Condoms (male or female) with or without spermicide
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- Diaphragm or cervical cap with spermicide
- Intrauterine device
- Hormonal contraception (combined estrogen and progestogen, or progestogen-only), including contraceptive implant or injectable
- Successful vasectomy in the male partner, considered successful if a woman reports that a male partner has:
- documentation of azoospermia by microscopy (1 year ago) or a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy
- Not of reproductive potential, such as having undergone hysterectomy, bilateral oophorectomy or tubal ligation, postmenopausal (any age and amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level > 40 IU/L), surgically sterile.
- Sexual abstinence. All participants born female who are not heterosexually active at screening must agree to utilize an acceptable method of contraception if they become heterosexually active as outlined above.
- All male participants should agree to use barrier contraception with their female partners for at least 2 weeks after vaccination.
- Has not shared the same enclosed living space with someone diagnosed with TB for one or more nights or for frequent or extended daytime periods during the 6 months prior to Study Day 1.
- HIV negative at screening.
- Negative clinical screening questionnaire and Xpert MTB/RIF negative sputum sample for pulmonary TB disease at screening.
Who cannot join
- Acute illness and/or axillary temperature ≥37.5°C on Study Day 1.
- Current suspicion or evidence (including but not limited to sputum Xpert MTB/RIF positive) of active TB disease at any CRC. An attempt must be made to obtain sputum from each participant; persons who are sputum unproductive will be assumed to be Xpert MTB/RIF negative.
- History of previous TB disease and/or treatment for TB disease.
- History of TB preventative therapy, not including BCG vaccination.
- Received any investigational drug or investigational vaccine within 42 days before Study Day 1, or planned use during the study period.
- Planned administration/administration of a licensed vaccine not foreseen by the study protocol in the period starting 28 days before Study Day 1 and ending 28 days after vaccine administration.
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- Prior receipt of any investigational TB vaccine candidate before Study Day 1. Note: receipt of placebo in a previous TB vaccine trial will not exclude a participant from participation if documentation is available and the Medical Monitor gives approval.
- Chronic administration of immunosuppressive medication within 42 days before Study Day 1 (inhaled and topical corticosteroids are permitted).
- Any confirmed or suspected immunosuppressive, immunodeficient, or autoimmune condition based on medical history and physical examination (no laboratory testing required).
- Concurrent, or planned participation in any other investigational study during the study period. (Concurrent participation in an observational trial not requiring blood or tissue sample collection is not an exclusion.)
- Received immunoglobulin or blood products within 42 days before Study Day 1, or planned administration during the study period.
- History or any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
- Pregnant or lactating/nursing female, or positive urine pregnancy test during screening or pre-vaccination on Study Day 1.
- Indeterminate IGRA test result at screening.
- Any current, or history of, medication use or medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, might compromise the safety of the participant or make it unlikely that the participant will comply with the protocol.
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
South Africa13 sites
JOSHA Research
Bloemfontein
South African Tuberculosis Vaccine Initiative
Cape Town
TASK Applied Science Pty Ltd. TASK Delft
Cape Town
UCTLI CLII - Centre for Lung Infection and Immunity
Cape Town
University of Cape Town Lung Institute PtyLtd. Centre for Tuberculosis Research Innovation
Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
Cape Town
Synergy Biomedical Research Institute
East London
TASK Eden Pty Ltd.
George
Perinatal HIV Research Unit
Johannesburg
Be Part Research Pty Ltd.
Paarl
The Aurum Institute Rustenburg Clinical Research Centre
Rustenburg
Desmond Tutu Health Foundation, Masiphumelele Research Office
Sunnydale
The Aurum Institute Tembisa Clinical Research Centre
Tembisa
Kenya2 sites
Victoria Biomedical Research Institute
Kisumu
Kenya Medical Research Institute
Nairobi
About this study
Official title: A Phase 2b, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy, Safety and Immunogenicity of a Candidate Tuberculosis (TB) Vaccine, MTBVAC, Against TB Disease in Adolescents and Adults Aged 14-45 Years, Living in a TB Endemic Region.
A Phase 2b, double-blind, randomized, placebo-controlled study to evaluate the efficacy, safety and immunogenicity of a candidate tuberculosis (TB) vaccine, MTBVAC, against TB disease in adolescents and adults aged 14-45 years, living in a TB endemic region.
Read the detailed description
Phase 2b, double-blind, randomized, placebo-controlled, safety and efficacy study in 5,500 healthy adults and adolescents. Participants will be enrolled based on IGRA status at baseline into an IGRA-positive cohort (n=4,300) or an IGRA-negative cohort (n=1,200). Most participants are likely to have received previous BCG vaccination in infancy. The investigational product is MTBVAC administered intradermally at 5x105 CFU.
Participants meeting the enrolment criteria will be randomized, in a 1:1 ratio if baseline IGRA-positive or in a 3:1 ratio if baseline IGRA-negative, to receive a single dose of MTBVAC or placebo administered intradermally on Study Day 1.
Participants will be followed up for efficacy following vaccination via regular visits or contacts to screen for possible TB. Participants will also be trained to recognize signs and symptoms consistent with pulmonary TB disease and to report them for clinical evaluation. Participants with clinical presumption of pulmonary TB will be assessed with confirmatory diagnostic testing using a Nucleic Acid Amplification Test (Xpert MTB/RIF Ultra assay) and microbiological culture in sputum sampled on 3 separate days within a 1 week period. Participants diagnosed with pulmonary TB will be referred for TB treatment according to local clinical practice.
Only HIV-negative participants will be eligible for enrolment. Participants will be tested for HIV seroconversion at the end of each year of follow-up and at the presumptive TB visits. Participants who test positive for HIV will be referred for TB preventive treatment and antiretroviral treatment according to local clinical practice.
A safety sub-cohort of approximately 660 participants (330 in each study arm) from the IGRA-positive cohort and 225 participants (150 MTBVAC and 75 placebo recipients) from the IGRA-negative cohort will be randomly selected for follow-up for solicited adverse events (AEs) and selected biochemistry and haematology. Additionally, an immunogenicity sub-cohort of approximately 90 participants (60 in the MTBVAC and 30 in the placebo arm) from the IGRA-positive cohort and 90 participants (60 in the MTBVAC and 30 in the placebo arm) from the IGRA-negative cohort will be randomly selected for specific immunogenicity assessments. All participants in the immunogenicity sub-cohort will participate in the safety sub-cohort. The sub-cohort randomization procedures will attempt to evenly distribute participants between adolescents (i.e., age 14 through 17) and adults (i.e., age 18 through 45) and among clinical research centres. The strategy for participant sub-cohort selection and randomization will be described in the Study Operations Manual (SOM) and Statistical Analysis Plan (SAP).
- Conditions
- Tuberculosis (TB)
- Being tested
- MTBVAC, Placebo
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTBVACBiological
Vaccine Dose: MTBVAC 5x10^5 Formulation (approximately, per standard dose): 3 - 17x10^5 CFU Sucrose Sodium glutamate Presentation: Lyophilized pellet in vials (10 doses) Volume: 0.1 mL/dose Intradermal
PlaceboBiological
0.9% saline Volume: 0.1 mL/dose Intradermal
| Study group | Role | What they receive |
|---|---|---|
| MTBVAC | Experimental | MTBVAC Receives: Biological: MTBVAC |
| Placebo | Placebo comparator | Placebo Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the protective efficacy of MTBVAC against bacteriologically confirmed PTB, not associated with HIV infection, diagnosed by more than one diagnostic test with sputum obtained before initiation of TB treatment, in baseline IGRA-positives.
Incident cases of definite pulmonary TB disease in baseline IGRA-positive participants with clinical suspicion of pulmonary TB disease, with Mtb identified by at least two positive diagnostic tests (two positive microbiological cultures or two positive Xpert MTB/RIF Ultra assays, or one positive of each) from sputum specimens taken before initiation of TB treatment and confirmed HIV-negative at the time of TB diagnosis, over a period starting 28 days following vaccination and lasting up to 36 months post vaccination.
Measured: 36 Months
Secondary outcomes (13)
To evaluate the protective efficacy of one dose of MTBVAC against bacteriologically confirmed pulmonary TB disease, not associated with HIV infection, diagnosed by more than one diagnostic test with sputum obtained before initiation of TB treatment.
Incident cases of definite pulmonary TB disease in baseline IGRA-positive and IGRA-negative participants with clinical suspicion of pulmonary TB disease, with M.tb identified by at least two positive diagnostic tests (two positive microbiological cultures or two positive Xpert MTB/RIF Ultra assays, or one positive of each) from sputum specimens taken before initiation of TB treatment and confirmed HIV-negative at the time of TB diagnosis, over a period starting 28 days following vaccination and lasting up to 36 months post-vaccination.
Measured: 36 Months
To evaluate the protective efficacy of one dose of MTBVAC against bacteriologically confirmed pulmonary TB disease, not associated with HIV infection, diagnosed with sputum obtained before initiation of TB treatment, as compared to placebo.
Incident cases of definite pulmonary TB disease in baseline IGRA-positive and IGRA-negative participants with clinical suspicion of pulmonary TB disease, with M.tb identified by microbiological culture or Xpert MTB/RIF Ultra from sputum specimens taken before initiation of TB treatment and confirmed HIV-negative at the time of TB diagnosis, over a period starting 28 days following vaccination and lasting up to 36 months post-vaccination.
Measured: 36 months
To evaluate the protective efficacy of one dose of MTBVAC against definite Xpert MTB/RIF Ultra positive pulmonary TB disease not associated with HIV infection, diagnosed with sputum obtained before initiation of TB treatment, as compared to placebo.
Incident cases of definite pulmonary TB disease in baseline IGRA-positive and IGRA-negative participants with clinical suspicion of pulmonary TB disease, with M.tb identified by Xpert MTB/RIF Ultra from sputum specimens taken before initiation of TB treatment and confirmed HIV-negative at the time of TB diagnosis, over a period starting 28 days following vaccination and lasting up to 36 months post-vaccination.
Measured: 36 months
To evaluate the protective efficacy of one dose of MTBVAC against clinical TB, as compared to placebo, in the entire study population.
Incident cases of clinical TB disease in baseline IGRA-positive and IGRA-negative participants diagnosed by a clinician who has decided to treat the participant with TB treatment, over a period starting 28 days following vaccination and lasting up to 36 months post-vaccination.
Measured: 36 Months
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with SAEs until Month 6 following vaccination.
Measured: 6 months
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with vaccine related SAEs during the entire study period.
Measured: 36 months
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with solicited injection site reactions and solicited systemic AEs in the safety sub-cohort during the 14 days following vaccination (day of vaccination and 14 subsequent days).
Measured: 28 Days
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with unsolicited AEs during the 28 days following vaccination (day of vaccination and 28 subsequent days).
Measured: 56 Days
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with unsolicited injection site reactions during the 84 days following vaccination (day of vaccination and 84 subsequent days).
Measured: 168 days
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with grade 3 or higher injection site reactions during the 84 days following vaccination (day of vaccination and 84 subsequent days).
Measured: 168 days
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with grade 2 or higher haematological and biochemical laboratory AEs, in the safety sub-cohort.
Measured: 36 months
To assess the safety and reactogenicity of one dose of MTBVAC, overall and stratified by IGRA status at baseline.
The proportion of participants with AESIs until Month 6 following vaccination.
Measured: 6 months
To assess the immunogenicity of one dose of MTBVAC via assessment of cell-mediated immune (CMI) responses in a subset of the enrolled participants, overall and stratified by IGRA status at baseline (immunogenicity sub-cohort only).
Evaluation of CMI responses with respect to components of the study vaccine, in the immunogenicity sub-cohort at Day 1 (prior to vaccination), Day 29, Month 12, Month 24 and Month 36 (if applicable).
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2024
- Study start19 Feb 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis (TB)Studies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International AIDS Vaccine Initiative
- Sponsor type
- Research network
- Collaborators
- Biofabri, SLU, Universidad de Zaragoza
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06272812
- Sponsor's protocol ID
- IAVI C113
- Status last verified
- Sep 2026
- First submitted
- 9 Feb 2024
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No