Pietermaritzburg

Researchers are evaluating the efficacy and safety of benralizumab, given as a subcutaneous injection, in children and adolescents aged 6 to under 18 years who have severe eosinophilic asthma. These patients have a history of asthma exacerbations and uncontrolled symptoms despite treatment with high-dose inhaled corticosteroids plus at least one other controller medication. This Phase III study aims to compare benralizumab to placebo in reducing the time to the first asthma exacerbation. The study includes a screening period lasting from 4 to 12 weeks to confirm eligibility. After screening, patients are randomly assigned in a 1:1 ratio to receive either benralizumab or placebo via subcutaneous injections during a double-blind treatment period lasting a minimum of 16 weeks. This period continues until the patient experiences an asthma exacerbation or a set number of events occur. Patients who exacerbate can enter an open-label extension where all receive benralizumab for at least 48 weeks. An end-of-treatment visit occurs 8 weeks after the last dose in the extension phase. Participants will be monitored through visits and assessments including confirmation of severe eosinophilic asthma, asthma control questionnaires, and symptom diaries. Researchers will measure the time to first asthma exacerbation as the primary outcome. Medication adherence is tracked during screening, and safety is monitored throughout both the double-blind and extension periods. Total participation may span over a year, considering screening, treatment, extension, and follow-up visits.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

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 the efficacy and safety of inavolisib combined with Phesgo compared to placebo with Phesgo as maintenance therapy in participants who have previously untreated HER2-positive advanced breast cancer with PIK3CA mutations. This Phase III, multicenter, randomized, double-blind, placebo-controlled study focuses on participants with locally advanced or metastatic breast cancer, aiming to understand the treatment impact after initial induction therapy. Participants will receive inavolisib orally once daily on Days 1 to 21 of each 21-day cycle, starting on Day 1 of Cycle 1 during maintenance treatment. Phesgo will be administered subcutaneously every three weeks on Day 1 of each cycle. The study includes an induction therapy phase where taxane-based chemotherapy is given after Phesgo. Optional endocrine therapy such as tamoxifen, aromatase inhibitors, or fulvestrant may be used based on the investigator's choice, with luteinizing hormone-releasing hormone agonists administered according to local guidelines. During the study, participants will be monitored for progression-free survival for up to approximately 40 months. Assessments include evaluation of heart function, organ function, and overall health status. Researchers will track the safety and effectiveness of the treatment combination through regular clinical evaluations and laboratory tests. The total duration includes maintenance treatment cycles and follow-up to measure outcomes and monitor safety.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

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 investigating whether the medicine vicadrostat, when taken together with empagliflozin, can lower the risk of heart-related problems in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. This study is a Phase III trial that compares the effects of vicadrostat plus empagliflozin to a placebo plus empagliflozin in people with these conditions. Participants are randomly assigned to one of two groups: one group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets that look like vicadrostat along with empagliflozin. All participants take one tablet daily for a period ranging from two and a half years up to four years and three months. Throughout the study, participants continue their usual medications for diabetes, high blood pressure, and cardiovascular disease. During up to 51 months of participation, participants visit the study site regularly where doctors collect health information and blood samples. Researchers track when participants experience cardiovascular events such as heart-related deaths or heart failure events. The study also monitors participants’ overall health and any side effects they may experience to assess the safety and effects of the treatments.

Researchers are evaluating an expanded social network recruitment to HIV testing (E-SNRHT) intervention in KwaZulu-Natal, South Africa, aiming to increase HIV testing rates among men and locate undiagnosed HIV cases. The study addresses HIV-related stigma, a key barrier to testing, by asking newly diagnosed individuals to recruit people in their broader social networks, beyond recent risk partners. This approach is designed to reduce stigma and increase testing among hard-to-reach groups, with previous pilots showing higher testing rates and reduced stigma. The study involves 32 Department of Health clinics randomly assigned to either the E-SNRHT intervention or control conditions. Newly diagnosed individuals at intervention clinics, called seeds, receive education on HIV transmission and are asked to recruit anyone in their expanded social networks who might benefit from HIV testing. Recruited network members are then tested for HIV, receive counseling, and are referred to antiretroviral treatment if positive or to follow-up testing if negative. Recruitment uses confidential coupons to link network members to recruiters while protecting privacy. Follow-up includes additional recruitment steps and continued support for treatment and testing. Participants complete baseline and 6-month follow-up interviews covering behaviors, stigma, social support, and HIV service use. Some network members also participate in in-depth interviews about their experiences. Researchers collect clinical data on treatment initiation and viral suppression, monitor implementation fidelity, and gather community-level stigma data. The study measures outcomes such as rates of men recruited for testing, new HIV diagnoses, stigma experiences, social support, and treatment cascade outcomes over the study period.

Researchers are exploring the feasibility and limited effectiveness of a co-developed health system strengthening program to support people living with severe mental illness (SMI) in South Africa. The study addresses the challenge of repeated hospital readmissions after acute psychiatric treatment, a common problem due to lack of community-based support in low- and middle-income countries. This pilot study is conducted in a South African district to test whether this program can reduce hospital readmissions and improve mental health outcomes for people with SMI. The intervention includes multiple components: improved referral processes across healthcare levels; psychosocial rehabilitation programs for hospital and primary care staff; refresher training for clinicians managing severe mental illness; structured outreach by community health workers after discharge; and a Household Champion program to empower caregivers. Registered counselors and community health workers will be trained to deliver these services. Participants are divided into two groups: one receives the full intervention package, and the other receives usual care with enhanced referral and discharge readiness support. Participants will be followed for four months after hospital discharge. Researchers will assess hospital readmission rates using medical records as the primary outcome. Additional measures include stigma, medication adherence, and recovery among service users, as well as qualitative evaluations of the intervention's acceptability, practicality, and potential for wider use. The study aims to generate important data on implementing community-based mental health support in low-resource settings, with a focus on feasibility and early effectiveness.

Researchers are evaluating the effect of balcinrenone/dapagliflozin compared with dapagliflozin alone on cardiovascular death and heart failure events in patients with chronic heart failure and impaired kidney function who recently experienced a heart failure event. This is a Phase III, international, randomized, double-blind, parallel-group, active-controlled study involving approximately 700 sites in about 40 countries. Participants will be randomly assigned in a 1:1:1 ratio to receive one of three treatments once daily: a capsule of balcinrenone/dapagliflozin 15 mg/10 mg with a placebo tablet, a capsule of balcinrenone/dapagliflozin 40 mg/10 mg with a placebo tablet, or a dapagliflozin 10 mg tablet with a placebo capsule. The study is event-driven, with an estimated average duration of 22 months that includes a screening period, a 20-month blinded treatment phase, and a one-month follow-up on open-label dapagliflozin. During the study, participants will be monitored for the time to first occurrence of cardiovascular death, heart failure hospitalization, or heart failure events without hospitalization over approximately 38 months. Assessments include clinical evaluations, laboratory tests, and safety monitoring throughout the study and follow-up period to track treatment effects and patient outcomes.