A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of H56:IC31 in Reducing the rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis (A-055)
* indicates required field
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).
| Number of Doses | Treatment Assignment N (planned) | Total N (planned) | |
| H56:IC31 5 μg H56/ 500 nmol IC31 | Placebo | ||
| All randomized participants 2 x 0.5 mL (Days 0, 56) intramuscularly in deltoid | 450 | 450 | 900 |
| First 150 randomized participants across all sites Safety cohort subgroup | 75 | 75 | 150 |
| First 100 randomized participants SATVI & MMRC sites only Immunogenicity cohort subgroup | 50 | 50 | 100 |
Primary Objective
To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for acid fast bacilli (AFB) on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative):
• Safety of H56:IC31 compared to placebo
Key Secondary Objective
To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for AFB on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative):
• Safety of H56:IC31 compared to placebo
Other Secondary Objectives
To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for AFB on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative):
• Trends towards efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease relapse
• Trends towards efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease reinfection
• Antigen-specific cell-mediated immune responses to H56:IC31
• Humoral immune responses to H56:IC31
Exploratory Objectives
To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for AFB on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative):
• Trends towards efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease by exploratory efficacy endpoint definitions (Section 2.1.4.1)
• Transcriptomic signatures of inflammation or associated with TB disease recurrence
• Immunological correlates of risk and correlates of protection for TB disease recurrence
• Humoral immune responses to H56:IC31in participants with TB recurrence diagnosis compared to the participants in the control cohort
Primary
- Rate of TB disease recurrence (relapse or reinfection), defined as TB diagnosed by confirmation of Mtb by culture of sputum. [Time Frame: During the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination]
- Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection)
Secondary
- Solicited adverse events and all adverse events occurring the first 14 days after each of the 1st and 2nd vaccinations [Time Frame: Day 0 thru Day 70]
- Safety of H56:IC31 compared to placebo
- Serious adverse events including medically important events occurring after the 1st vaccination through the end of the trial [Time Frame: Day 0 thru Day 421]
- Safety of H56:IC31 compared to placebo
- Efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease relapse [Time Frame: Day 0 thru Day 421]
- 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
- Efficacy of H56:IC31 compared to placebo in reducing the rate of TB disease reinfection [Time Frame: Day 0 thru Day 421]
- 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.
- Antigen-specific cell-mediated immune responses to H56:IC31 [Time Frame: Day 0 thru Day 70]
- 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
- Humoral immune responses to H56:IC31 [Time Frame: Day 0 thru Day 70]
- 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
South Africa
Cape Town Locations
- Bellville, Cape Town, South Africa, 7530
Task Clinical Research Centre
- Mowbray, Cape Town, South Africa
University of Cape Town Lung Institute
Gauteng Locations
- Tembisa, Gauteng, South Africa, 1632
The Aurum Institute: Tembisa Clinical Research Centre
North-West Locations
- Klerksdorp, North-West, South Africa, 2570
The Aurum Institute
Western Cape Locations
- Cape Town, Western Cape, South Africa, 6850
South African Tuberculosis Vaccine Initiative, Project Office, Brewelskloof Hospital , Harlem Street, Worcester
Tanzania
- Mbeya, Tanzania
NIMR Mbeya Medical Research Centre
NCT03512249
Jan. 31, 2020
March 30, 2024