MTBVAC vaccine to prevent tuberculosis in adolescents and adults in high-TB areas.

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.

This trial will test a single intradermal dose of the MTBVAC vaccine versus placebo to see if it prevents TB in HIV-negative adolescents and adults aged 14–45 living in TB-endemic regions.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5500 (estimated)
• Ages: 14 Years to 45 Years
• Sex: All
• Sponsor: International AIDS Vaccine Initiative (Research network)
• Locations: 16 sites (Kisumu and 15 other locations)
• Trial ID: NCT06272812 on ClinicalTrials.gov

What this trial studies

This is a Phase 2b, double-blind, randomized, placebo-controlled study enrolling about 5,500 healthy adolescents and adults to measure safety, immune response, and protection against pulmonary TB. Participants are grouped by baseline IGRA status into an IGRA-positive cohort (about 4,300) randomized 1:1 and an IGRA-negative cohort (about 1,200) randomized 3:1 to receive MTBVAC or placebo. Most participants are expected to have had BCG in infancy; MTBVAC is given as a single intradermal dose of 5x10^5 CFU. Follow-up includes regular symptom screening, diagnostic testing with Xpert MTB/RIF Ultra and culture for suspected TB, and referral for standard TB treatment when disease is confirmed.

Who should consider this trial

Good fit: Ideal candidates are HIV-negative individuals aged 14–45 who live in TB-endemic areas, are in generally good health, and can attend study visits and follow-up.

Not a fit: People who are HIV-positive, pregnant, outside the 14–45 age range, have active TB, or cannot adhere to follow-up would not be eligible and therefore would not receive benefit from participation.

Why it matters

Potential benefit: If successful, MTBVAC could directly reduce cases of pulmonary TB in adolescents and adults and help lower transmission in endemic communities.

How similar studies have performed: Earlier Phase 1/2 studies of MTBVAC have shown acceptable safety and immunogenicity, but large-scale proof of efficacy against TB disease has not yet been established.

Eligibility criteria

Inclusion Criteria:

1. Is male or female aged 14 through 45 years on Study Day 1.
2. 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.
3. 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)
4. Has general good health as confirmed by medical history and physical examination.
5. 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:

   1. Condoms (male or female) with or without spermicide
   2. Diaphragm or cervical cap with spermicide
   3. Intrauterine device
   4. Hormonal contraception (combined estrogen and progestogen, or progestogen-only), including contraceptive implant or injectable
   5. 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
   6. 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.
   7. 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.
6. All male participants should agree to use barrier contraception with their female partners for at least 2 weeks after vaccination.
7. 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.
8. HIV negative at screening.
9. Negative clinical screening questionnaire and Xpert MTB/RIF negative sputum sample for pulmonary TB disease at screening.

Exclusion Criteria:

1. Acute illness and/or axillary temperature ≥37.5°C on Study Day 1.
2. 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.
3. History of previous TB disease and/or treatment for TB disease.
4. History of TB preventative therapy, not including BCG vaccination.
5. Received any investigational drug or investigational vaccine within 42 days before Study Day 1, or planned use during the study period.
6. 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.
7. 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.
8. Chronic administration of immunosuppressive medication within 42 days before Study Day 1 (inhaled and topical corticosteroids are permitted).
9. Any confirmed or suspected immunosuppressive, immunodeficient, or autoimmune condition based on medical history and physical examination (no laboratory testing required).
10. 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.)
11. Received immunoglobulin or blood products within 42 days before Study Day 1, or planned administration during the study period.
12. History or any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
13. Pregnant or lactating/nursing female, or positive urine pregnancy test during screening or pre-vaccination on Study Day 1.
14. Indeterminate IGRA test result at screening.
15. 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.

Where this trial is running

Kisumu and 15 other locations

• Victoria Biomedical Research Institute — Kisumu, Kenya (Recruiting)
• Kenya Medical Research Institute — Nairobi, Kenya (Recruiting)
• JOSHA Research — Bloemfontein, South Africa (Recruiting)
• South African Tuberculosis Vaccine Initiative — Cape Town, South Africa (Recruiting)
• TASK Applied Science Pty Ltd. TASK Delft — Cape Town, South Africa (Recruiting)
• UCTLI CLII - Centre for Lung Infection and Immunity — Cape Town, South Africa (Recruiting)
• University of Cape Town Lung Institute PtyLtd. Centre for Tuberculosis Research Innovation — Cape Town, South Africa (Recruiting)
• Wellcome Centre for Infectious Diseases Research in Africa — Cape Town, South Africa (Recruiting)
• Synergy Biomedical Research Institute — East London, South Africa (Recruiting)
• TASK Eden Pty Ltd. — George, South Africa (Recruiting)
• Perinatal HIV Research Unit — Johannesburg, South Africa (Recruiting)
• Be Part Research Pty Ltd. — Paarl, South Africa (Recruiting)
• The Aurum Institute Rustenburg Clinical Research Centre — Rustenburg, South Africa (Recruiting)
• Desmond Tutu Health Foundation, Masiphumelele Research Office — Sunnydale, South Africa (Not_yet_recruiting)
• The Aurum Institute Tembisa Clinical Research Centre — Tembisa, South Africa (Recruiting)
• Ifakara Health Institute — Dar es Salaam, Tanzania (Not_yet_recruiting)

Study contacts

• Study coordinator: Elana Van Brakel, MD

Conditions Tuberculosis