Rustenburg

Researchers are evaluating quabodepistat-based treatment regimens for adults and adolescents aged 14 years and older with rifampicin-resistant or multidrug-resistant pulmonary tuberculosis (RR/MDR-TB). This Phase 3, randomized, open-label, multicenter trial aims to determine if quabodepistat combined with other tuberculosis drugs can shorten treatment to 4 months and offer similar or better effectiveness and safety compared to the current 6-month WHO-recommended treatments. The study includes two main groups based on fluoroquinolone sensitivity: fluoroquinolone-sensitive and fluoroquinolone-resistant RR/MDR-TB. Participants will be randomly assigned to receive either experimental or control treatments. For fluoroquinolone-sensitive RR/MDR-TB, the experimental regimen is BPaQM (bedaquiline, pretomanid, quabodepistat, moxifloxacin) for 4 months, compared to the control BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months. For fluoroquinolone-resistant RR/MDR-TB, the experimental treatment is BPaQ (bedaquiline, pretomanid, quabodepistat) for 6 months, versus the control BPaL (bedaquiline, pretomanid, linezolid) for 6 months. Drug dosing schedules vary by regimen, with bedaquiline dosing starting with daily doses followed by maintenance doses and all other drugs dosed once daily. Participants will be followed for 16 months after randomization, during which time researchers will assess treatment effectiveness by measuring the proportion of participants with unfavorable outcomes up to 12 months following randomization. Safety and tolerability will be monitored through recording adverse events from the first dose until two weeks after treatment ends. The study includes sputum sample collection, chest X-rays, laboratory tests, and monitoring for side effects. Independent committees oversee data monitoring and outcome adjudication to ensure participant safety and study integrity.

Researchers are evaluating the safety, immune response, and effectiveness of a new tuberculosis vaccine called MTBVAC in healthy adolescents and adults aged 14 to 45 years who live in areas where TB is common. This Phase 2b study is randomized, double-blind, and placebo-controlled, involving participants with different immune responses to TB exposure as determined by IGRA testing. The study aims to protect against TB disease confirmed by multiple tests and focuses on those who are HIV-negative. Participants will be randomly assigned to receive either a single intradermal dose of the MTBVAC vaccine or a placebo. The vaccine dose contains approximately 5x10^5 colony-forming units, and the placebo is saline solution, both given as 0.1 mL injections. The study includes two groups based on IGRA status: one with prior immune response to TB and one without, with different randomization ratios. Some participants will be part of safety and immune response sub-cohorts for more detailed monitoring. Throughout the 36-month follow-up, participants will attend regular visits or be contacted to check for signs of TB. They will be trained to recognize TB symptoms and report them for further evaluation, including sputum testing using advanced molecular and culture methods. HIV testing will occur yearly and at times of suspected TB. Safety monitoring includes tracking adverse events and laboratory tests in selected subgroups. Participants diagnosed with TB will be referred for treatment according to local guidelines.

Researchers are evaluating the safety and immune response of the MTBVAC vaccine in adolescents and adults aged 12 to 55 years living with or without HIV in South Africa. The study focuses on comparing MTBVAC to the BCG vaccine and is conducted as a Phase 2a clinical trial. Participants are grouped based on HIV status, CD4+ T cell counts, and IGRA status to better understand the vaccine's effects in different subpopulations. The study is divided into two parts, with Part A including two cohorts and Part B having one cohort, each with four groups. Participants are randomized to receive either a single 0.1 mL injection of MTBVAC or BCG vaccine intradermally. Enrollment in the third cohort will begin only if safety criteria are met for the first two cohorts. All participants receive one dose and are followed for 48 weeks to monitor outcomes. Participants will undergo various assessments throughout the study, including monitoring for adverse events up to 48 weeks and evaluating immune cell responses at baseline and weeks 4 and 10. Researchers will track solicited and unsolicited adverse events, serious adverse events, and Grade 3 or higher adverse events. Safety, immune responses, and overall health will be carefully observed through clinical exams, laboratory tests, and questionnaires during the study period.

Researchers are conducting a Phase 3, double-blinded, placebo-controlled, multicenter trial to assess whether azithromycin taken as a preventive treatment can reduce death rates in adults with advanced HIV disease. Participants eligible for the study must have confirmed HIV infection with low CD4 counts or specific treatment histories, reflecting advanced immunosuppression. The trial aims to better understand mortality outcomes related to this preventive approach in this population. Participants will be randomly assigned to receive either azithromycin tablets or placebo tablets for 28 days. All participants will be followed for 24 weeks after randomization to measure the main outcome of death from any cause, with total follow-up lasting 48 weeks. The study compares the effects of azithromycin prophylaxis against an inactive placebo to evaluate its impact on survival. During the study, participants will be monitored regularly to track health outcomes, particularly mortality. They must be able to start or adjust antiretroviral therapy within four weeks of joining the trial. Researchers will closely observe for any adverse effects, treatment adherence, and overall health status throughout the follow-up period to assess the safety and effectiveness of the intervention.

Researchers are evaluating new drug regimens for treating adults with drug-susceptible pulmonary tuberculosis (TB) in a Phase 2 adaptive, randomized, controlled, open-label trial. The study aims to determine if these novel treatments provide better early effectiveness compared to the standard combination of isoniazid, rifampicin, pyrazinamide, and ethambutol. The safety and tolerability of these regimens will also be assessed over an 8-week treatment period. Participants will receive one of several drug combinations, including standard therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol, or experimental regimens containing drugs like bedaquiline, pretomanid, linezolid, TBI-223, and sutezolid. Dosing varies by drug, with most taken orally once daily, often with meals. The initial 8 weeks constitute the study treatment phase, followed by an 18-week continuation phase of standard care, making the total treatment duration 26 weeks. Throughout the study, participants will undergo regular assessments, including sputum cultures to measure bacterial growth rates during the first 6 weeks and monitoring for any serious side effects by week 8. Laboratory tests, chest x-rays, and performance scores will be used to evaluate health status. Participants will be followed for a total of 52 weeks, ensuring safety and treatment effectiveness are closely monitored.