Soweto

Researchers are looking for new medicines to prevent HIV-1 (Human Immunodeficiency Virus Type 1) infection. The goals of this study are to learn: * If taking MK-8527 once a month works to prevent HIV-1 infection as well as or better than a standard (usual) pre-exposure prophylaxis (PrEP) taken once a day * About the safety of MK-8527 and if people tolerate it

This research aims to evaluate the effectiveness, safety, and tolerability of two doses of remibrutinib compared to placebo in people aged 12 years and older with moderate to severe hidradenitis suppurativa, a chronic skin condition. The study is a phase 3 clinical trial involving participants with a diagnosis lasting at least six months and active symptoms in multiple body areas. The purpose is to determine how well remibrutinib works and how safe and tolerable it is for this condition. The trial lasts a total of 76 weeks and includes several parts: a screening period of up to 4 weeks, a first treatment period of 16 weeks where participants receive either remibrutinib Dose A, Dose B, or placebo in a double-blind manner, followed by a second treatment period lasting 52 weeks during which all participants receive remibrutinib doses. After treatment, there is a 4-week safety follow-up without treatment. Participants stopping treatment early are encouraged to continue in the study and complete the safety follow-up. During the study, participants will be regularly monitored for their response to treatment, including the proportion who achieve a clinical response measure called HiSCR50 at Week 16. Assessments will include physical exams and safety checks throughout the treatment periods and follow-up. The study seeks to gather detailed information on how remibrutinib affects the severity of hidradenitis suppurativa and participants' overall health during and after treatment.

This research aims to evaluate the safety and effectiveness of BMS-986504, a selective PRMT5 inhibitor, when combined with Nab-paclitaxel and Gemcitabine, compared to a placebo combined with Nab-paclitaxel and Gemcitabine. The study focuses on participants with untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC) who have a specific genetic alteration called homozygous MTAP deletion. This is a randomized Phase 2/3 trial designed to explore treatment options for this patient population. Participants will be assigned to receive either BMS-986504 at specified doses on certain days along with Nab-paclitaxel and Gemcitabine, or a placebo with the same chemotherapy drugs. The treatments are given according to protocol schedules. Some participants may have received up to one cycle of Nab-paclitaxel and Gemcitabine before starting the study treatment, provided they did not experience disease progression or intolerable side effects. The initial cycle must be completed before randomization. During the study, researchers will monitor participants for progression-free survival and overall survival for up to three years after the last participant is randomized. Assessments include measuring tumor response using established criteria (RECIST v1.1). Participants will undergo evaluations to track safety, treatment effects, and disease status throughout the trial period.

Researchers are evaluating the safety and effectiveness of divarasib combined with pembrolizumab compared to pembrolizumab with pemetrexed and either carboplatin or cisplatin. The study focuses on adults with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. This is a Phase III trial aiming to improve first-line treatment options for these patients. Participants will receive one of two treatment combinations. One group will take divarasib orally once daily along with pembrolizumab given through an intravenous infusion every three weeks. The other group will receive pembrolizumab with pemetrexed and either carboplatin or cisplatin, all administered by intravenous infusion every three weeks. Treatment schedules and dosages are carefully monitored during the study. Throughout the study, participants will be regularly assessed for progression-free survival and overall survival, with follow-up lasting up to approximately five years. Researchers will perform various evaluations including tumor measurements and safety monitoring. This long-term observation helps to understand the treatments' effects and safety over time, supporting informed decisions for future lung cancer therapies.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole compared to placebo plus CDK4/6i and letrozole. This study focuses on participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. It aims to assess treatment outcomes in the first-line setting for this specific breast cancer type. Participants will be assigned to receive either oral inavolisib once daily or a matching oral placebo once daily. All participants will also receive a CDK4/6 inhibitor on either Days 1-21 or Days 1-28 of each 28-day cycle, along with daily oral letrozole. This randomized, double-blind study will compare these two treatment combinations to monitor differences in disease progression and safety. Throughout the study, researchers will evaluate progression-free survival from the time of randomization until disease progression or death, up to 7 years. Participants will undergo assessments including tumor measurements by RECIST criteria, performance status evaluations, and monitoring of blood and organ function before treatment begins. Safety and efficacy will be closely observed during treatment, aiming to provide detailed long-term data on the study therapies.

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.

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 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 comparing the effectiveness of two treatments for participants with stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) who have PD-L1 expression of 1% or higher. This phase 3, randomized, open-label study focuses on first-line treatment options and aims to evaluate overall survival over up to five years for participants with PD-L1 levels between 1% and 49%. The trial involves participants with measurable disease and good performance status who have not received prior systemic therapy for advanced disease. The study compares a combination of Nivolumab and Relatlimab plus chemotherapy against Pembrolizumab plus chemotherapy. Chemotherapy drugs include Carboplatin, Pemetrexed, and Cisplatin, administered at specified doses on scheduled days. Participants are randomly assigned to receive either the Nivolumab and Relatlimab combination with chemotherapy or Pembrolizumab with chemotherapy as their initial treatment. Treatment schedules and doses are defined but not detailed here. Participants will be closely monitored throughout the study, which may last up to five years. Researchers will assess overall survival as the primary outcome, along with regular imaging tests like CT or MRI to measure disease status. Eligibility screening includes assessing PD-L1 levels, performance status, and other health factors. Safety monitoring and follow-up will continue to evaluate treatment effects and participant well-being during and after treatment.

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.