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 interferon gamma release assay positive adolescents and adults aged 14-45 years, living in a TB endemic region.
Phase 2b, double-blind, randomized, placebo-controlled, safety and efficacy study in 4,300 healthy adults and with a positive interferon gamma release assay (IGRA) test result. Most participants are likely to have received previous BCG vaccination in infancy. The investigational product is MTBVAC administered intradermally at 5x10\^5 CFU. Participants meeting the enrolment criteria will be randomized in a 1:1 ratio 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 and 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 sub-cohort of approximately 640 participants (320 in each study arm) will be selected for follow-up for solicited adverse events (AE) and selected chemistry and complete blood count (CBC). Additionally, a sub-cohort of approximately 430 participants (215 in each study arm) will be selected for specific immunogenicity assessments. The strategy for participant sub-cohort selection will be described in the Study Operations Manual (SOM).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
The Aurum Institute Tembisa Clinical Research Centre
Johannesburg, South Africa
RECRUITINGTo evaluate the protective efficacy of of MTBVAC against bacteriologically confirmed pulmonary TB disease, diagnosed by more than one diagnostic test with sputum obtained before initiation of TB treatment as compared to placebo.
Incident cases of definite pulmonary TB disease in participants with clinical suspicion of pulmonary TB disease, with Mtb identified by at least two positive diagnostic tests (microbiological culture, Xpert MTB/RIF Ultra, or both) 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.
Time frame: 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 participants with clinical suspicion of pulmonary TB disease, with Mtb identified by microbiological culture and/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.
Time frame: 36 Months
To evaluate the protective efficacy of MTBVAC candidate vaccine against definite Xpert MTB/RIF Ultra positive pulmonary TB disease diagnosed with sputum obtained before initiation of TB treatment, as compared to placebo.
Incident cases of definite pulmonary TB disease in participants with clinical suspicion of pulmonary TB disease, with Mtb 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 last vaccination.
Time frame: 36 months
To evaluate the protective efficacy of one dose of MTBVAC candidate vaccine against clinical TB, as compared to placebo
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Masking
QUADRUPLE
Enrollment
4,300
Incident cases of clinical TB disease diagnosed by a clinician who has decided to treat the patient with TB treatment, over a period starting 28 days following vaccination and lasting up to 36 months post last vaccination
Time frame: 36 months
To assess the safety and reactogenicity of one dose of MTBVAC candidate vaccine.
Occurrence of all SAEs until Month 6 following vaccination.
Time frame: 6 Months
To assess the safety and reactogenicity of one dose of MTBVAC candidate vaccine.
Occurrence of vaccine related SAEs during the entire study period.
Time frame: 36 months
To assess the safety and reactogenicity of one dose of MTBVAC candidate vaccine.
Occurrence of solicited local and systemic AEs in the safety sub-cohort during the 7 days following vaccination (day of vaccination and 6 subsequent days).
Time frame: 7 Days
To assess the safety and reactogenicity of one dose of MTBVAC candidate vaccine.
Occurrence of unsolicited AEs during the 28 days following vaccination (day of vaccination and 27 subsequent days).
Time frame: 28 Days
To assess the safety and reactogenicity of one dose of MTBVAC candidate vaccine.
Occurrence of grade 3 or higher injection site reactions during the 84 days following vaccination (day of vaccination and 84 subsequent days).
Time frame: 84 Days
To assess the safety and reactogenicity of one dose of MTBVAC candidate vaccine.
Occurrence of grade 2 or higher haematological and chemistry abnormalities, in the safety sub-cohort.
Time frame: 36 months
To assess the immunogenicity of one dose of the MTBVAC candidate vaccine via assessment of humoral and cell-mediated immune (CMI) responses in a subset of the enrolled participants.
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).
Time frame: 36 months
To assess the immunogenicity of one dose of the MTBVAC candidate vaccine via assessment of humoral and cell-mediated immune (CMI) responses in a subset of the enrolled participants.
Evaluation of humoral immune 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).
Time frame: 36 months