This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups. * H56:IC31 (investigational vaccine) * Placebo 900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment. 5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively. 1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).
This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups. * H56:IC31 (investigational vaccine) * Placebo 900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment. 5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI)) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively. 1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR). Preclinical data suggest H56:IC31 may be more efficacious if administered while patients are still on treatment. Following the national guidelines for TB treatment in South Africa and Tanzania, we will obtain sputum samples from patients towards the end of treatment at about the same time they are obtained within the national TB control programmes, and if the sputum is smear negative, the criterion for successful treatment within TB programmes, the individual will be eligible for randomization and vaccination towards the end of their six-month treatment period. As this is a proof of concept TB vaccine study, HIV positive individuals have been excluded as it is not yet known what effect HIV infection may have on the immune response to the vaccine. However, HIV positive individuals are an important population to include in future studies should efficacy be demonstrated in this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
831
Task Clinical Research Centre
Bellville, Cape Town, South Africa
University of Cape Town Lung Institute
Mowbray, Cape Town, South Africa
The Aurum Institute: Tembisa Clinical Research Centre
Tembisa, Gauteng, South Africa
The Aurum Institute
Klerksdorp, North West, South Africa
South African Tuberculosis Vaccine Initiative , Project Office, Brewelskloof Hospital , Harlem Street, Worcester
Cape Town, Western Cape, South Africa
NIMR Mbeya Medical Research Centre
Mbeya, Tanzania
• Rate of TB disease recurrence (relapse or reinfection), defined as TB diagnosed by confirmation of Mtb by culture of sputum.
Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection)
Time frame: During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination
Solicited adverse events and all adverse events occurring the first 14 days after each of the 1st and 2nd vaccinations
Safety of H56:IC31 compared to placebo
Time frame: Day 0 thru Day 70
Serious adverse events including medically important events occurring after the 1st vaccination through the end of the trial
Safety of H56:IC31 compared to placebo
Time frame: Day 0 thru Day 421
Efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease relapse
Rate of TB relapse defined as subjects meeting the primary endpoint of TB disease recurrence, AND determined by whole genome sequencing (WGS) of the Mtb isolate to be the same strain of Mtb as in the subject's original isolate from the time of diagnosis
Time frame: Day 0 thru Day 421
Efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease reinfection
Rate of TB disease reinfection defined as subjects meeting the primary endpoint of TB disease recurrence, AND determined by WGS of the Mtb isolate to be a different strain than in the subject's original isolate from the time of diagnosis.
Time frame: Day 0 thru Day 421
Antigen-specific cell-mediated immune responses to H56:IC31
Antigen-specific cell-mediated immune responses by peripheral blood mononuclear cells (PBMC) intracellular cytokine staining (ICS) at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70) and at TB recurrence diagnosis
Time frame: Day 0 thru Day 70
Humoral immune responses to H56:IC31
Humoral immune responses by IgG ELISA of plasma samples at baseline (V3= Day 0) and 14 days after the 2nd vaccination (V6= Day 70) and at TB recurrence diagnosis
Time frame: Day 0 thru Day 70
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