Pietermaritzburg

Researchers are investigating new treatments for metastatic cervical cancer, which is cancer that has spread beyond the cervix, the lower part of the uterus. This study evaluates the safety and effectiveness of the antibody drug conjugate sacituzumab tirumotecan sac-TMT combined with pembrolizumab and bevacizumab. The goal is to find out if these treatments, given together or with some variations, help patients live longer or delay cancer progression compared to standard care. The study has two parts. In Part 1, participants receive sac-TMT, pembrolizumab, and bevacizumab together to assess safety. In Part 2, all participants first get standard induction treatment with pembrolizumab, paclitaxel, and cisplatin or carboplatin, possibly with bevacizumab. Those whose cancer does not worsen then enter maintenance treatment, where they are randomly assigned to receive either pembrolizumab alone or sac-TMT plus pembrolizumab, with optional bevacizumab. Participants are involved for up to about 20 months during maintenance treatment after up to 4 months of induction. The study monitors safety by tracking side effects and treatment discontinuations. Effectiveness is measured by progression-free survival and overall survival up to several years. Quality of life and physical functioning are also assessed through questionnaires. Treatments and evaluations occur through regular intravenous infusions and periodic monitoring visits.

Researchers are evaluating the effectiveness and safety of a combination inhaler containing fluticasone propionate and albuterol sulfate, delivered via a multidose dry powder inhaler with an electronic module, in participants aged 12 years and older with asthma. This Phase 3 trial aims to compare this combination treatment to fluticasone propionate alone, albuterol sulfate alone, or a placebo inhaler. The study also assesses different dosing schedules, safety, tolerability, and pharmacokinetics of these inhalers. Participants will be randomly assigned to one of four groups receiving either the combination inhaler, fluticasone propionate inhaler, albuterol sulfate inhaler, or placebo, all with integrated electronic modules. Treatments are administered over a 4-week period with dosing four times daily. Pharmacokinetic assessments will be conducted after a single dose administration. The study is double-blind and placebo-controlled, with a parallel group design. Throughout the approximately 10-week study period, including screening and treatment, participants will undergo evaluations including lung function tests measuring forced expiratory volume in one second FEV1, asthma control questionnaires, and safety assessments. Researchers will monitor treatment-emergent adverse events and measure blood concentrations of the inhaled drugs. The study includes electronic monitoring of inhaler use and collects data at baseline, during treatment, and at week 4, with follow-up to assess efficacy and safety.

Researchers are evaluating the safety and effects of a new medicine called NNC0487-0111 in people who have Heart Failure with preserved Ejection Fraction HFpEF or Heart Failure with mildly reduced Ejection Fraction HFmrEF and excess body weight. This phase 3 clinical trial aims to find out if NNC0487-0111 is safe and effective for treating these conditions compared to a placebo. Participants have HFpEF or HFmrEF and a body mass index of 30 or above. The study is sponsored by Novo Nordisk AS and uses a randomized, quadruple-masked design. Participants will receive either NNC0487-0111 or a matching placebo by injection under the skin once a week. The NNC0487-0111 is given in increasing doses over time. The study is parallel in design, meaning participants are randomly assigned to one of the two groups and receive that treatment throughout the trial. This treatment period extends for up to about 165 weeks. The study evaluates the time to certain heart failure events, hospitalizations, cardiovascular deaths, and other major cardiovascular events. During the study, participants will be monitored regularly to assess heart failure outcomes and kidney function, as well as quality of life using questionnaires like the Kansas City Cardiomyopathy Questionnaire. Safety and effectiveness are assessed through hospital visits, heart failure event tracking, and blood tests including kidney function and blood sugar levels. The total participation spans over three years, with ongoing evaluations to measure the time to heart failure events and cardiovascular outcomes. Participants receive close medical monitoring throughout the study period.

Researchers are evaluating camizestrant against standard endocrine therapy for patients with ER-positive, HER2-negative early breast cancer who have an intermediate or high risk of disease recurrence. These patients must have completed locoregional therapy and at least 2 to 5 years of standard adjuvant endocrine therapy. The study is a Phase III open-label trial focused on improving outcomes for these patients over a long-term period. Participants are randomly assigned to receive either camizestrant orally or continue with the standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors exemestane, letrozole, anastrozole or tamoxifen. Treatment in each group lasts for 60 months. The study allows prior use of CDK46 inhibitors and includes a follow-up period extending up to 10 years from the last patient randomization. During the study, participants will undergo regular assessments to monitor invasive breast cancer-free survival and other outcomes such as invasive disease-free survival, distant relapse-free survival, overall survival, and safety. Researchers will also evaluate symptoms like joint pain, hot flushes, and vaginal dryness using specific scales, along with quality of life measures and pharmacokinetics. Safety monitoring continues up to 28 days after the last dose, and participants remain under observation for up to 10 years total.

Researchers are evaluating new medicines to prevent infection with Human Immunodeficiency Virus Type 1 HIV-1. This Phase 3 clinical trial aims to find out if taking MK-8527 once a month is more effective than a daily standard pre-exposure prophylaxis PrEP in preventing HIV-1 infection in women. The study also monitors the safety and tolerability of MK-8527 compared to standard treatment. Participants are randomly assigned to one of two groups one group receives 11 mg of MK-8527 once monthly along with a placebo daily pill resembling EmtricitabineTenofovir Disoproxil Fumarate FTCTDF, and the other group receives the daily FTCTDF pill plus a monthly placebo resembling MK-8527. This treatment phase lasts for up to approximately two years. Afterward, all participants take open-label FTCTDF daily for an additional 28 days. During the study, participants attend regular visits for up to about two years, during which researchers check for new HIV-1 infections, record any adverse events or side effects, and monitor if participants stop the study medication due to side effects. The primary outcomes include the number of participants who acquire HIV-1 infection, those who experience adverse events, and those who discontinue due to adverse events, all tracked over the treatment period.

Researchers are evaluating the effectiveness and safety of inavolisib combined with Phesgo compared to a placebo combined with Phesgo as maintenance treatment for participants with previously untreated HER2-positive advanced breast cancer that has a PIK3CA mutation. This Phase 3 study focuses on participants with locally advanced or metastatic breast cancer who have completed induction therapy. Participants first receive induction therapy with Phesgo plus taxane-based chemotherapy. Following this, they enter the maintenance phase where they are randomly assigned to receive either inavolisib tablets taken orally once daily for 21 days of each 21-day cycle along with Phesgo administered subcutaneously every 3 weeks, or a matching placebo tablet with Phesgo on the same schedule. Optional endocrine therapy may be given based on the investigators choice according to standard care. Throughout the study, participants undergo regular monitoring including tumor assessments, quality of life questionnaires, and safety evaluations lasting up to approximately 111 months. Key outcomes measured include progression-free survival assessed by investigators, overall survival, response rates, duration of response, and adverse event rates. Plasma concentrations of inavolisib are also measured at specific timepoints. Participants will be followed closely during and after treatment to assess these outcomes over an extended period.

Researchers are evaluating the treatment of rifampicin-resistant tuberculosis RR-TB by comparing nurse-led care in primary care clinics to the standard physician-led care at district hospitals in South Africa. This multi-site, cluster randomized, non-inferiority trial aims to assess treatment outcomes, safety, and patient-related costs over a five-year period, including patients with or without HIV co-infection. The study addresses the high costs and access barriers associated with hospital-based RR-TB care and explores the potential benefits of decentralized, patient-centered models closer to patients homes. The trial includes two groups one receiving nurse-led RR-TB treatment at primary care clinics with nurses available once or twice weekly on a rotating schedule, and the other receiving standard physician-led outpatient treatment at district hospitals. Nurses manage RR-TB treatment while physicians typically cover multiple clinics with limited availability. The trial assesses whether nurse-led treatment in primary care clinics is not inferior to physician-led hospital outpatient treatment regarding treatment success and safety. Participants aged 18 and older with new RR-TB diagnoses are involved in regular assessments including laboratory tests, ECGs, and monitoring for adverse events over 12 months. Researchers evaluate treatment outcomes at 6 months, severe adverse events, and patient costs at 12 months, along with secondary measures like time to treatment initiation, culture conversion, HIV treatment milestones, and provider adherence to guidelines. The study includes safety monitoring and cost-effectiveness evaluations, with a total participation duration varying based on individual treatment timelines.

Researchers are evaluating the effects of vicadrostat combined with empagliflozin in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. The study aims to assess whether this combination can help reduce cardiovascular risks compared to a placebo with empagliflozin. This Phase III trial involves adults with these conditions who are already receiving treatment for them. Participants are randomly assigned to one of two groups. One group takes vicadrostat and empagliflozin tablets daily, while the other group takes placebo tablets that look like vicadrostat but have no active medicine, alongside empagliflozin. Treatment lasts from two and a half years up to four years and three months. All participants continue their usual medications for diabetes, blood pressure, and heart disease during the study. Throughout the study, lasting up to four years and three months, participants visit the study site regularly for health checks and blood samples. Doctors monitor cardiovascular events and any side effects experienced. The main outcome measured is the time until the first cardiovascular death or heart failure event. Other health indicators like blood pressure and kidney function are also tracked to understand the effects of the treatment combination.

Researchers are evaluating an expanded social network recruitment to HIV testing E-SNRHT intervention in South Africa to address the challenge of locating undiagnosed HIV cases and reducing HIV-related stigma. This study focuses on increasing HIV testing among men, who are less likely to seek testing, by encouraging peer recruitment beyond risk partners to include any social contacts. The study is a site-randomized trial involving 32 Department of Health clinics in KwaZulu-Natal, comparing E-SNRHT to usual care to assess its impact on testing rates, stigma, social support, and treatment outcomes. The intervention recruits newly diagnosed HIV-positive individuals seeds from clinics assigned to the E-SNRHT condition, who receive education about HIV transmission and are asked to recruit members of their expanded social networks for HIV testing. These network members are then tested and referred to treatment if positive or to follow-up testing if negative. The study uses recruitment coupons to maintain confidentiality and extends recruitment to secondary network members through a two-step process. Control clinics provide standard HIV testing and care without the expanded recruitment. Participants complete baseline interviews covering demographics, behaviors, stigma, and social support, with follow-up interviews at six months to track HIV-related behaviors and treatment outcomes. The study includes qualitative interviews with a subset to explore experiences of peer recruitment and stigma. Researchers will collect clinic data on ART initiation and viral suppression, monitor implementation fidelity, and evaluate intervention effects on male testing rates, new HIV diagnoses, stigma, social support, and HIV care cascade outcomes over the study period ending in 2027.

Researchers are evaluating a health system strengthening intervention designed to support people living with severe mental illness SMI in South Africa. This study aims to determine the feasibility, appropriateness, and limited efficacy of a co-developed program to reduce hospital readmissions following acute psychiatric hospitalization. The research focuses on addressing the cycle of readmission by improving community-based care in a low-resource setting, building on partnerships and government collaboration in the uMgungundlovu District. The intervention includes multiple components improved referral pathways across healthcare levels psychosocial rehabilitation programs delivered by multidisciplinary teams and registered counselors refresher training for primary healthcare clinicians a community mental health education and detection toolkit for outreach teams and a Household Champion program to empower caregivers. Participants are randomly assigned to receive either this full intervention package or standard care with improved hospital-level referral and discharge processes. Participants will be monitored for 4 months after hospital discharge. Assessments include hospital readmission rates, recovery scores, internalized stigma, and treatment adherence, measured through questionnaires and medical records. Researchers will also collect qualitative data on the interventions acceptability, demand, implementation, practicality, adaptation, integration, and potential for expansion. This combination of data will provide insight into the programs feasibility and limited efficacy in reducing psychiatric relapse in the community.