East London

This research aims to evaluate the safety and effectiveness of iza-bren, a bi-specific antibody-drug conjugate targeting EGFR and HER3 with a topoisomerase inhibitor, compared to the treatment of physician's choice (paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, or capecitabine). The study focuses on patients with previously untreated, locally advanced, recurrent inoperable, or metastatic triple-negative breast cancer (TNBC) or estrogen receptor (ER)-low, HER2-negative breast cancer who are not eligible for anti-PD(L)1 or endocrine therapies. The trial is conducted in two phases, phase 2 and phase 3, to thoroughly assess these treatments.

Researchers are evaluating new medicines to prevent Human Immunodeficiency Virus Type 1 (HIV-1) infection, focusing on women assigned female at birth who are cisgender. This Phase 3 clinical trial aims to determine whether taking the drug MK-8527 once a month is more effective than the usual daily pre-exposure prophylaxis (PrEP) medication in preventing HIV-1 infection. The study also seeks to understand the safety and tolerability of MK-8527 in this population. Participants will be randomly assigned to receive one of several oral tablets: MK-8527 once monthly, a standard daily PrEP medication called Emtricitabine/tenofovir disoproxil (FTC/TDF), or placebo tablets matched to each drug. This double-blind study compares these groups to assess both the effectiveness and side effects of MK-8527 over time. During the study, participants will be monitored for up to about two years to track new HIV-1 infections, any adverse events they experience, and whether they stop taking the study medication due to side effects. Researchers will regularly evaluate participants' health, safety, and adherence to the treatment plan throughout this period.

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 examining the feasibility of Coach Mpilo, a peer support intervention tailored for men with tuberculosis (TB) and HIV in South Africa. Men tend to have worse TB outcomes and less treatment success, so this study aims to address those gender disparities. The study focuses on men starting TB treatment, including those co-infected with HIV, to evaluate if this support method can improve treatment completion and HIV viral suppression. Participants will receive Coach Mpilo, where trained peer coaches with TB and HIV treatment experiences help men navigate and stay on their treatment plans. The study has two parts: one assessing Coach Mpilo for men with TB alone, and another for men with both TB and HIV. Men will be randomized to either receive Coach Mpilo or the usual clinic-based support. The study will also tailor Coach Mpilo based on participant feedback before the main evaluation. Men enrolled will be followed for up to 210 days, during which researchers will collect data on treatment feasibility, acceptability, safety, and completion rates. They will also monitor adherence to anti-retroviral therapy and viral suppression for those with HIV. The study will use interviews, simulations, and a randomized controlled trial design to gather information and assess outcomes related to retention in care and successful treatment.

Researchers are evaluating the safety and bactericidal activity of TBD09 combined with other drugs in adults with drug-sensitive pulmonary tuberculosis. This Phase 2, open-label, randomized trial aims to assess whether TBD09, when used with bedaquiline, pretomanid, and linezolid, shows potential as a safe and effective treatment option for this condition. Participants are divided into five groups, each receiving different doses or combinations of TBD09 alongside bedaquiline and pretomanid or linezolid for 28 days. Group 1 receives TBD09 100 mg three times weekly, Groups 2 to 4 receive TBD09 daily at increasing doses (100 mg, 300 mg, 500 mg), and Group 5 receives linezolid 600 mg daily instead of TBD09. All treatments are administered daily or three times weekly depending on the group. Throughout the study, participants are monitored for bactericidal activity from randomization through Day 28 and safety from screening through Day 35. Researchers evaluate serious adverse events, treatment-emergent adverse events, adverse events of special interest, and events leading to treatment discontinuation. These assessments help determine the safety and effectiveness of the study treatments over the course of participation.

Researchers are evaluating a nurse-led treatment approach for rifampicin-resistant tuberculosis (RR-TB) in primary care clinics compared to the standard physician-led treatment at district hospitals in South Africa. This multi-site, cluster randomized, non-inferiority trial spans five years and aims to assess treatment outcomes, safety, and patient costs. The study includes participants from KwaZulu-Natal, Gauteng, and Eastern Cape provinces and considers patients regardless of HIV status. The trial compares nurse-led RR-TB care delivered in primary care clinics, where nurses visit once or twice weekly on a rotating schedule, to physician-led outpatient care in hospitals. This approach aims to create equal access and management responsibilities between the two models. The nurse-led care model is designed to be patient-centered and closer to patients' homes, following World Health Organization recommendations for decentralized treatment of RR-TB with six-month regimens. Participants will be closely monitored throughout the study, with assessments covering treatment outcomes at six months, safety through severe adverse events over twelve months, and evaluation of patient-related catastrophic costs within a year. Researchers will also examine treatment initiation times, microbiological conversion, HIV treatment progress, adherence to dosing guidelines, and cost-effectiveness. The study involves thorough clinical and laboratory evaluations, including access to necessary labs, X-rays, and ECGs, with ongoing safety and effectiveness monitoring over the trial duration.

Researchers are evaluating the impact of Undetectable Equals Untransmittable (U=U) messaging on improving HIV care for men in two provinces of South Africa. The study focuses on increasing HIV testing uptake, starting antiretroviral treatment (ART), achieving viral suppression, and retaining men in care. The U=U message emphasizes that people living with HIV who take ART and maintain an undetectable viral load cannot sexually transmit the virus. This research aims to close the gender gap in HIV care and support global targets to reduce HIV incidence and improve health outcomes by 2030. The study involves two behavioral interventions using U=U messaging. On designated testing days, trained health promoters will invite men nearby to get tested using U=U messaging scripts. Men who test positive will receive U=U messaging from counselors at testing sites to encourage clinic-based ART initiation. After starting treatment, participants will receive additional U=U adherence messages from research counselors, including business cards with brief messages, monthly SMS reminders, and in-clinic booster messages during routine medical visits. Participants will be followed to measure HIV testing and ART initiation within 30 days, and viral load suppression at six months. The study includes assessments through counseling sessions, message delivery, and monitoring of treatment adherence and retention in care. The research will also conduct evaluations to guide future U=U messaging efforts. Total participation duration depends on individual treatment timelines but includes ongoing support and follow-up to assess outcomes.

Researchers are evaluating a new rapid test called the NG lateral flow assay (LFA) to detect Neisseria gonorrhoeae infection in pregnant and symptomatic women attending clinics in East London, South Africa. Gonorrhea remains a serious health issue, especially for pregnant women, as untreated infections can cause complications such as miscarriage and preterm birth. This study aims to assess the test's accuracy, acceptability, and usability in this population, addressing concerns that pregnancy-related changes may affect test performance. The study involves testing vaginal samples collected by healthcare providers and by the women themselves using the NG LFA. Results from the NG LFA will be compared to the standard laboratory test, Xpert CT/NG, to determine diagnostic accuracy. The NG LFA is designed to provide rapid results within 30 minutes and is intended to be easy to use and affordable, making it suitable for use in antenatal care (ANC) clinics and primary healthcare settings. The study will also compare the safety and acceptability of self-collected versus provider-collected samples in both pregnant and symptomatic non-pregnant women. Participants will attend clinics where vaginal samples will be collected and tested using both the NG LFA and standard laboratory methods. Researchers will measure test sensitivity and specificity, evaluate user preferences, and monitor the safety of self-collection. The study focuses on women aged 18 years and older who are either pregnant and attending ANC or symptomatic non-pregnant women. These assessments will help determine if the NG LFA can be effectively implemented in routine care to improve gonorrhea detection and treatment.

Researchers are evaluating the effects of baxdrostat combined with dapagliflozin compared to dapagliflozin alone in adults aged 40 and older who have type 2 diabetes, established cardiovascular disease, a history of hypertension with systolic blood pressure of at least 130 mmHg at screening, and at least one additional risk factor for heart failure. This Phase III randomized, placebo-controlled, event-driven study aims to determine if the combination reduces the risk of heart failure events or cardiovascular death, with follow-up lasting up to 38 months. Participants who meet screening criteria but are not currently treated with SGLT2 inhibitors or have been treated for less than 4 weeks will enter a run-in period receiving dapagliflozin 10 mg once daily for 4 to 6 weeks before randomization. The study involves random assignment to either baxdrostat plus dapagliflozin or placebo plus dapagliflozin. Site visits occur at approximately 2, 4, 8, 16, and 34 weeks after randomization, then every 4 months. Participants discontinuing the blinded study drug may continue open-label dapagliflozin, with ongoing visits and data collection as per protocol. Participants will undergo an optional pre-screening period without site visits or consent to help identify eligibility, followed by up to 14 days of formal screening after informed consent. Researchers will monitor heart failure events and cardiovascular deaths as primary outcomes. Safety and adherence will be tracked throughout the study, including during any premature discontinuation of blinded treatment. The study will conclude when a predetermined number of secondary endpoint events have occurred, with continued follow-up as needed.