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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 the efficacy and safety of iza-bren, a bi-specific antibody-drug conjugate targeting EGFR and HER3 with a chemotherapy payload, compared to treatment chosen by physicians including paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, and capecitabine for patients with first-line metastatic triple-negative breast cancer TNBC or low estrogen receptor ER-low, HER2-negative breast cancer who cannot receive anti-PDL1 or endocrine therapies. This study includes adults with locally advanced, recurrent inoperable, or metastatic disease who meet specific eligibility criteria. Participants are randomly assigned to receive iza-bren or one of the physicians choice chemotherapy regimens. The treatments are given at specified doses on scheduled days. The study includes two phases Phase 2 to determine the recommended dose of iza-bren and Phase 3 to compare progression-free survival and other outcomes. The study will last several years, with follow-up extending up to approximately 47 months after randomization. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests, and monitoring for adverse events. Quality of life questionnaires will also be completed. Researchers will track progression-free survival, overall survival, treatment-related side effects, tumor size changes, and patient-reported outcomes to evaluate the treatments. The total participation duration may extend up to several years depending on treatment response and follow-up requirements.

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 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.

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 investigating the efficacy and safety of duvakitug in people with moderately to severely active Crohns Disease in a multinational, multicenter, randomized, double-blind, placebo-controlled Phase 3 study. The trial includes three sub-studies aiming to evaluate duvakitugs effects compared to placebo during induction treatment phases, focusing on clinical remission and endoscopic response at 12 weeks. Participants receive subcutaneous injections of duvakitug or placebo following the study protocol. The study duration can be up to 35 weeks, including a screening period of up to 5 weeks, followed by a 12-week induction phase in either Sub-Study 1 open-label, Sub-Study 2 pivotal induction, or Sub-Study 3 extended induction for non-responders. A 6-week follow-up period applies to participants not entering the maintenance study. Throughout the trial, participants undergo scheduled visits for assessments including clinical remission based on Crohns Disease Activity Index and endoscopic scores. Safety is monitored with reports of adverse events and serum drug levels. Up to 8 to 15 visits are planned depending on the sub-study, with follow-up continuing for 45 days after the last dose for those not moving to maintenance treatment.

Men tend to have worse outcomes throughout the tuberculosis TB care process, including less symptom reporting, diagnosis, and treatment completion, especially when also living with HIV. This research evaluates the feasibility of Coach Mpilo CM, a peer-support intervention originally designed to help men with HIV, adapted here for men with TB and TBHIV co-infection. The study aims to assess how well this coaching model works for men starting TB treatment and for those co-infected with HIV, focusing on treatment completion and viral suppression as key outcomes. The study includes two main groups men beginning TB treatment who receive either the CM peer support or usual clinic-based care, and men co-infected with TB and HIV who receive the adapted CM support or standard care. The CM intervention involves trained peer coaches with personal experience in TB and HIV treatment providing support and guidance to help men stay on their treatment plans. Participants will be randomized to either the CM support or standard care in a controlled trial. Participants will be followed through their TB treatment and beyond, with assessments of how feasible, acceptable, and safe the CM intervention is for men. Researchers will measure TB treatment completion within 180 days and, for those with HIV, adherence to antiretroviral therapy and viral load suppression up to 210 days. The study involves interviews, simulations, and monitoring of treatment progress to gather data on outcomes and inform future larger trials. Total participation lasts through treatment and follow-up periods of about 6 to 7 months.

Researchers are evaluating the safety and bactericidal activity of TBD09 combined with other drugs in adults with drug-sensitive pulmonary tuberculosis. This Phase 2 randomized trial aims to determine if these combinations are safe and effective for treating this form of tuberculosis. The study is sponsored by the Gates Medical Research Institute and involves multiple treatment groups with varying doses of TBD09. Participants are assigned to one of five groups receiving different combinations of TBD09, bedaquiline, pretomanid, and linezolid. The TBD09 doses vary from 100 mg three times weekly to 500 mg daily, combined with bedaquiline and pretomanid, or linezolid with bedaquiline and pretomanid. Treatment lasts for 28 days in each group. During the study, participants will be monitored through Day 35 for safety, including serious adverse events, treatment-emergent adverse events, and adverse events leading to treatment discontinuation. Researchers will also assess bactericidal activity up to Day 28 and study pharmacokinetics of TBD09. Additional safety evaluations include blood tests, visual and color vision assessments, and peripheral neuropathy screening. The total participation period covers screening, treatment, and follow-up assessments.

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 impact of Undetectable Equals Untransmittable UU messaging and counseling on improving HIV care among men in two South African provinces. The study aims to increase HIV testing uptake and antiretroviral treatment ART initiation, as well as to improve viral suppression and retention in care. This research builds on evidence that men living with HIV face testing and treatment gaps compared to women, and that addressing these gaps may reduce new HIV infections among women and help achieve global HIV targets by 2030. The study involves two main interventions using human-centered, behavioral nudge-informed UU messaging. In Aim 1, trained health promoters use UU messaging scripts during community-based HIV testing to encourage men to get tested and link those testing positive to ART services. In Aim 2, men starting or restarting ART receive UU adherence messages alongside standard counseling, including monthly SMS and in-clinic booster messages to support treatment adherence and viral suppression. Comparison groups receive standard care messaging for testing and treatment. Participants will be followed to assess outcomes including ART initiation within 30 days of testing invitation and viral load suppression at 6 months. Additional measures include testing agreement rates at baseline and retention in care at 12 months. The study includes informed consent, monthly follow-ups, and multi-method evaluations to inform future UU messaging programs. Total participation time varies by individual progress through the testing and care cascade.