Rustenburg

Researchers are evaluating quabodepistat-containing treatment regimens for adults and adolescents aged 14 years and older with rifampicin-resistant or multidrug-resistant pulmonary tuberculosis RRMDR-TB. The study aims to determine if adding quabodepistat to other TB drugs can shorten treatment duration to 4 months for fluoroquinolone-sensitive TB and provide a safer alternative compared to the current 6-month WHO-endorsed regimens. This Phase 3, randomized, open-label trial also compares treatments for patients with fluoroquinolone-resistant TB. Participants will be divided into two main groups based on fluoroquinolone sensitivity. Those with fluoroquinolone-sensitive RRMDR-TB will receive either an experimental 4-month regimen BPaQM bedaquiline, pretomanid, quabodepistat, moxifloxacin or a 6-month control regimen BPaLM bedaquiline, pretomanid, linezolid, moxifloxacin. Those with fluoroquinolone-resistant RRMDR-TB will receive either an experimental 6-month regimen BPaQ bedaquiline, pretomanid, quabodepistat or a control 6-month regimen BPaL bedaquiline, pretomanid, linezolid. Dosing schedules vary by regimen and last either 4 or 6 months. During the 16-month follow-up, participants will undergo regular assessments including sputum samples, chest X-rays, laboratory tests, and safety evaluations. Researchers will measure treatment effectiveness by the proportion with unfavorable outcomes 12 months after randomization and monitor adverse events. Additional outcomes include time to sputum culture conversion, microbiological relapse, and drug plasma levels. Safety will be closely monitored throughout treatment and follow-up periods.

This research aims to evaluate the antiviral effects of S-337395 compared with a placebo in adults who are not hospitalized but have respiratory syncytial virus RSV infection and are at high risk of progressing to severe disease. Participants must start treatment within 72 hours of showing RSV symptoms. The study is a Phase 2b trial and involves adults with specific risk factors such as older age and chronic lung or cardiovascular disease. Participants will be randomly assigned to receive either a high dose or low dose of S-337395, or a matching placebo. The treatment is given orally twice daily for up to 5 days. The study is double-blind, meaning neither participants nor researchers know which treatment is being administered during the trial. Throughout the study, participants will be monitored closely with assessments including nasal swabs to measure RSV RNA levels at several time points up to day 6. Researchers will also track symptoms using questionnaires and record any side effects up to 28 days. Blood samples will be collected to measure drug levels, and safety will be monitored throughout the study, which runs until December 2026.

Researchers are evaluating the efficacy, safety, and immune response of MTBVAC, a candidate vaccine against tuberculosis TB, in adolescents and adults aged 14 to 45 years living in regions where TB is common. This Phase 2b study is randomized, double-blind, and placebo-controlled, aiming to compare MTBVAC to a placebo in preventing TB disease, particularly in participants who have tested positive or negative for latent TB infection using IGRA tests. Most participants likely received BCG vaccination in infancy. Participants are assigned to receive a single intradermal dose of MTBVAC at 5x105 CFU or placebo on Study Day 1. Those who test IGRA-positive at baseline are randomized 11 to either MTBVAC or placebo, while IGRA-negative participants are randomized 31. Subgroups of participants will be closely monitored for safety and immune responses, with specific evaluations in selected safety and immunogenicity sub-cohorts. The study also includes follow-up screening for pulmonary TB disease and HIV testing yearly and during suspected TB episodes. During the study, participants will attend regular visits or have contacts to monitor for TB signs and symptoms, with sputum tests performed if TB is suspected. Safety assessments include monitoring adverse events and laboratory tests in sub-cohorts. The main outcome is the protective effect of MTBVAC against bacteriologically confirmed pulmonary TB over 36 months, along with safety and immune response evaluations. Participants diagnosed with TB will be referred for standard treatment, and those who seroconvert for HIV will receive appropriate care. The study runs until March 2028.

Researchers are evaluating the safety and immune response of the MTBVAC vaccine in adolescents and adults aged 12 to 55 years living with and without HIV in South Africa. The study includes participants grouped by HIV status and immune markers, such as CD4 T cell counts and interferon-gamma release assay results. The trial is designed to compare MTBVAC with the BCG vaccine and is conducted as a Phase 2a randomized study without a placebo group. The study is divided into two parts Part A includes two cohorts with four groups each, and Part B includes one cohort with four groups. Participants receive a single 0.1 mL intradermal injection of either MTBVAC or BCG in the upper arm at the start of the study. Enrollment of the third cohort will occur only if safety criteria are met in the first two cohorts. Following vaccination, participants are monitored for 48 weeks. Participants will attend clinic visits for safety assessments and immune response evaluations through blood tests measuring specific immune cells and antibodies at various time points, including weeks 4, 10, 24, and 48. Researchers will track adverse events, vaccine acceptability, and immune system changes by analyzing blood samples and gene expression. The study ensures thorough follow-up to assess both the safety and the bodys immune reaction to the vaccines over nearly a year.

Researchers are evaluating whether taking azithromycin as a preventive treatment can reduce the risk of death in adults with advanced HIV disease. This is a Phase 3, double-blind, placebo-controlled trial involving multiple centers. The study aims to understand if azithromycin prophylaxis can lower mortality compared to a placebo in this vulnerable population. Participants will be randomly assigned to receive either an oral azithromycin tablet or a matching placebo tablet once daily for 28 days. After this treatment period, they will be followed for 24 weeks to measure the main outcome of all-cause mortality. The total study participation will last 48 weeks to monitor both short-term and longer-term effects. During the study, participants will undergo assessments to track survival and hospitalizations at 12 and 24 weeks after starting the treatment. Researchers will closely monitor health outcomes and any hospital stays to evaluate the impact of azithromycin prophylaxis. Safety and adherence will be followed throughout the trial to ensure accurate measurement of results.

Researchers are evaluating the safety and effectiveness of two sorfequiline-based treatment regimens combined with pretomanid and linezolid for adults aged 18 to 65 years with newly diagnosed, drug-sensitive pulmonary tuberculosis. This phase 2, randomized, multi-center clinical trial aims to compare a loading dose regimen against a steady dose regimen. The study focuses on adults who have smear-positive pulmonary tuberculosis and have not been recently treated for the disease. The primary goal is to assess safety through treatment-emergent adverse events and other health measures, while also exploring effectiveness and drug behavior in the body. Participants will be randomly assigned to one of two treatment groups. One group receives sorfequiline 200 mg daily for 4 weeks followed by 100 mg daily for 13 weeks, along with pretomanid 200 mg and linezolid 600 mg daily. The other group receives sorfequiline 100 mg daily for 17 weeks, with pretomanid and linezolid dosed the same way. All treatments are taken orally once daily with food. The study includes a screening period, a 17-week treatment period, and a follow-up period lasting 52 weeks after treatment ends. During the study, participants will undergo various assessments including safety monitoring through adverse event reporting, ECGs, vital signs, laboratory tests, vision checks, and neuropathy evaluations. Effectiveness will be measured by the time to stable sputum culture conversion and favorable treatment outcomes at 26 and 52 weeks post-treatment. Researchers will also study drug levels and quality of life. The total participation time spans from screening through one year after completing treatment, with regular visits throughout the treatment and follow-up phases.

Researchers are evaluating new drug combinations for treating adults with drug-susceptible pulmonary tuberculosis TB in this Phase 2 randomized trial. The study aims to compare the early effectiveness and safety of these novel regimens against the current standard treatment, which includes isoniazid, rifampicin, pyrazinamide, and ethambutol. The main goal is to see if these new treatments improve early bacterial clearance and maintain acceptable safety over an 8-week period. Participants will be assigned to receive one of several drug regimens during the first 8 weeks. These include the standard treatment or experimental combinations containing bedaquiline, pretomanid, linezolid, TBI-223, or sutezolid at various doses. After the initial 8 weeks, all participants continue with standard therapy for an additional 18 weeks. Medication is taken orally daily, with dosing adjusted by weight and specific guidelines. During the 52-week study, which covers the full treatment and follow-up period, participants will have regular assessments including sputum tests to measure bacterial growth, blood tests to monitor safety, and clinical evaluations. The main outcomes measured are changes in bacterial growth over the first 6 weeks and the occurrence of significant side effects by week 8. Additional measurements include culture conversion rates, adverse events up to week 26, and overall cure rates at 52 weeks. Participants will be closely monitored throughout for safety and treatment response.