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Researchers are evaluating the safety and effectiveness of bomedemstat MK-3543 compared to the best available therapy BAT in adults with essential thrombocythemia ET who have not responded well to or cannot tolerate hydroxyurea. The study aims to determine if bomedemstat provides a better lasting clinical and blood response than current treatments. This is a phase 3, randomized, open-label trial sponsored by Merck Sharp Dohme LLC. Participants will be randomly assigned to receive either bomedemstat or one of several approved therapies including anagrelide, busulfan, interferon alfa or pegylated forms, or ruxolitinib. Bomedemstat will start at 50 mg daily, with dose adjustments to safely lower platelet counts. Each participant will be treated daily for up to 52 weeks, with an option to continue an extended treatment phase up to 156 weeks. Those initially on BAT who stop responding may switch to bomedemstat during the extension. During the study, participants will have regular assessments of blood counts, symptoms, and side effects. Researchers will measure the durable clinicohematologic response over about 52 weeks as the main outcome. Other outcomes include symptom changes, event rates like thrombosis or bleeding, disease progression, and safety up to 180 weeks. The study includes monitoring of fatigue and quality of life using patient questionnaires to understand treatment impact over time.

Researchers are evaluating the safety and tolerability of an investigational drug called elritercept, both alone and in combination with the JAK inhibitor ruxolitinib, in adults with myelofibrosis MF. The study also aims to understand how elritercept affects the signs and symptoms of MF, how the body processes the drug, and its effects on anemia when used with or without ruxolitinib. This is a Phase 2 open-label study focusing on participants with anemia related to MF.

Researchers are evaluating momelotinib in adults with low-risk myelodysplastic syndromes LR-MDS who have anemia requiring red blood cell transfusions. The study aims to find out if momelotinib is safe and effective by testing different doses and observing how the body processes the drug. This is a Phase 2, randomized, open-label trial sponsored by GlaxoSmithKline focusing on patients with specific risk classifications of MDS and transfusion needs. Participants will receive momelotinib at one of two dose levels to determine the optimal dose. The study involves monitoring drug levels in the blood and assessing changes in red blood cell transfusion requirements. The treatment period lasts up to 24 weeks for primary outcomes, with extended safety and response monitoring continuing for up to approximately 133 weeks. Throughout the trial, participants will have regular evaluations including blood tests, assessments of anemia improvement, and monitoring for any side effects or adverse events. The main outcomes measured include the percentage of participants achieving transfusion independence for at least 12 weeks and safety events related to treatment. Participants will be followed for up to about 2.5 years to evaluate long-term effects and drug processing in the body.

Researchers are evaluating how the drug roginolisib works when combined with ruxolitinib in adults with myelofibrosis MF who have not responded adequately to prior JAK inhibitor treatments. This Phase III open-label study aims to assess the safety and tolerability of this combination treatment in patients with intermediate or high-risk MF. About 26 male and female patients aged 18 or older, who have been on stable doses of ruxolitinib for at least 3 months without significant spleen size reduction, will participate. Participants will receive roginolisib at a dose of 80 mg equivalent to 72 mg roginolisib alongside ruxolitinib up to 25 mg twice daily. The study starts with 13 patients in Part 1 to evaluate initial safety and potential benefits, followed by 13 more patients in Part 2 to further understand the effects of this combination. The treatment cycles are 28 days long, and the treatment period is expected to last up to 52 weeks. During the study, participants will have regular assessments including monitoring of adverse events, ECGs, laboratory tests, and blood pressure at specific days within each cycle. Researchers will also measure biomarker responses, spleen size reduction, symptom improvements, and drug levels in the blood. Participants will be followed for overall survival every 12 weeks for up to 96 weeks after enrollment of the last patient, with symptom assessments at baseline, 12 and 24 weeks. Safety and tolerability will be closely monitored throughout the study period.

Researchers are evaluating elritercept compared to epoetin alfa to treat anemia in adults with very low, low, or intermediate risk myelodysplastic syndromes MDS who need regular red blood cell RBC transfusions. The study aims to assess how elritercept affects the need for RBC transfusions, its safety, and whether it improves tiredness and quality of life compared to epoetin alfa. The trial also explores the immune response to elritercept and monitors medical problems related to the treatment. Participants will be randomly assigned to receive either elritercept or epoetin alfa. Those receiving elritercept will start with a dose of 3.75 mgkg by subcutaneous injection every 4 weeks, which may be increased to 5.0 mgkg if necessary. Participants receiving epoetin alfa will start at 450 IUkg by subcutaneous injection once weekly, with possible dose escalation up to 1050 IUkg. Treatment will continue with monitoring over several cycles, each lasting 28 days, with assessments up to 48 weeks and potential follow-up to about 5 years. During the study, participants will have regular visits to assess their need for RBC transfusions, hemoglobin levels, fatigue using the FACIT-Fatigue Scale, quality of life through questionnaires, and blood tests to monitor drug levels and immune response. The main outcome is the proportion of participants who become independent of RBC transfusions for at least 12 consecutive weeks with improved hemoglobin. Safety and overall health will be closely monitored, including tracking any progression to acute myeloid leukemia or death. The total participation duration may last up to several years to evaluate long-term effects.

This research aims to collect long-term safety and efficacy data for participants who have been using bomedemstat and are benefiting from it, or have achieved blood count remission in certain conditions. The study includes individuals with essential thrombocythemia ET, polycythemia vera PV, and myelofibrosis MF who have previously been in earlier bomedemstat trials. It does not involve hypothesis testing but focuses on extended monitoring. Participants will take oral bomedemstat capsules once daily for up to 10 years. The dose they start with will be the same as they used in their previous study before transitioning into this extension. This allows continuous assessment of the effects and safety of the medication over a long period. During the study, participants will be closely monitored for adverse events and any reasons for stopping treatment due to side effects. For those with ET or PV, the duration of their clinical response and remission will be tracked, as well as any progression to more severe conditions. Other outcomes include the frequency of blood clots and bleeding events. Participant involvement may last up to about 10 years, with regular assessments and safety checks throughout.

Researchers are evaluating the efficacy and safety of bomedemstat compared with hydroxyurea in adults diagnosed with essential thrombocythemia ET who have not previously received cytoreductive therapy but require it. The main goal is to see if bomedemstat can provide a better durable clinicohematologic response DCHR than hydroxyurea. This Phase 3, randomized, double-blind trial aims to improve treatment options for people with ET by comparing these two therapies. Participants will be randomly assigned to receive either active bomedemstat with a placebo for hydroxyurea or active hydroxyurea with a placebo for bomedemstat. Both treatments are given as oral capsules daily for up to 52 weeks, with doses adjusted to safely reduce platelet counts within a target range. After completing the initial treatment period, eligible participants may continue treatment in an extended phase. Placebos will be stopped and unblinding will occur once all participants finish or discontinue the 52-week therapy. During the study, participants will have regular assessments to monitor blood counts, symptom changes using specific fatigue and symptom questionnaires, and the occurrence of thrombotic or hemorrhagic events. Researchers will evaluate durable hematologic remission and disease progression up to Week 52. Safety will be closely followed through adverse event tracking. The total study participation includes the initial 52-week treatment and possible extension, with detailed monitoring throughout to assess treatment effects and safety.

The trial investigates complicated intra-abdominal infections cIAIs, focusing on whether a fixed extended duration of 28 days of antibiotics is better than the standard care duration, which typically lasts 7 to 18 days. This is a multicenter, randomized controlled trial that aims to assess cost effectiveness and the rate of treatment failure over 180 days. The study responds to concerns that current treatments result in high relapse and extra-abdominal infection rates, while also addressing the balance between antibiotic resistance and treatment adequacy. Participants are randomly assigned to one of two groups one receiving antibiotics for a fixed duration of 28 days, and the other receiving standard care where the antibiotic duration is decided by their clinician. The trial will recruit 1166 adult patients from ICUs and hospital wards across about 30 NHS trust hospitals. Both groups receive antibiotics as prescribed, with the difference being the length of treatment determined by randomization. During the study, participants will complete quality of life questionnaires at the start and at 30, 60, and 180 days after randomization. They will also provide information on antibiotic use and healthcare resources. Researchers will review hospital records to track admissions, relapses, additional infections, and various health outcomes such as treatment failure within 180 days. The study is sponsored by the University of Leeds and includes comprehensive follow-up to evaluate clinical results and economic impact.

Researchers are evaluating treatments for community-acquired pneumonia CAP, especially in patients admitted to intensive care units ICUs. This trial also adapts to study treatments for respiratory pandemics like COVID-19. The goal is to determine which treatment strategies improve outcomes for patients with severe pneumonia, using a flexible, ongoing approach that can test multiple therapies simultaneously and update as new information becomes available. Participants receive different treatment strategies based on random assignment to study groups. Treatments include various antibiotics, steroids, antivirals, immune modulators, anticoagulation methods, and ventilation strategies. Some treatment options have been closed to recruitment, reflecting the trials adaptive nature. The trial includes several domains targeting specific infections such as influenza and COVID-19, with dosing and duration guided by clinical practice and local guidelines. During the study, participants are monitored closely with assessments including survival up to 90 days, days alive without organ support in ICU, ICU and hospital length of stay, ventilator-free days, organ failure-free days, and quality of life up to 6 months. Researchers collect detailed data on patient outcomes, organ support needs, and hospital discharge status. The study runs until February 2028, with ongoing evaluation to improve pneumonia treatment strategies in ICU settings and during respiratory pandemics.

Researchers are studying whether adding navtemadlin to ruxolitinib treatment can provide more benefit than ruxolitinib alone for adults with Myelofibrosis who have not responded well to ruxolitinib by itself. This Phase 3 trial includes patients who are new to JAK inhibitor treatment and have a confirmed diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia Myelofibrosis. The study aims to assess improvements in spleen size and symptom reduction over 24 weeks, as well as long-term outcomes like disease progression and overall survival. Participants first receive ruxolitinib alone during a run-in period to identify those with suboptimal response. Those qualifying are randomly assigned in a 21 ratio to receive either navtemadlin or a placebo as an add-on to their ongoing ruxolitinib. Navtemadlin or placebo is taken orally once daily for 7 days followed by 21 days off in 28-day cycles, while ruxolitinib is taken twice daily continuously. The study is double-blinded so neither participants nor researchers know which add-on treatment is given. During the trial, participants will undergo evaluations including spleen volume measurements and symptom assessments at 24 weeks. They will be monitored for disease progression and survival for up to 8 years. The study includes regular check-ups to track side effects, treatment adherence, and overall health status. These detailed assessments help researchers understand the potential benefits and safety of adding navtemadlin for patients with Myelofibrosis.