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Researchers are evaluating the safety and effectiveness of bomedemstat (MK-3543) compared with the best available therapy (BAT) in adults with essential thrombocythemia (ET) who have not responded well to or cannot tolerate hydroxyurea. This phase 3 clinical trial aims to determine if bomedemstat provides a better durable clinicohematologic response in these participants. Participants will receive either bomedemstat as an oral capsule or one of the best available therapies, including anagrelide (oral capsule), busulfan (oral tablet), interferon alfa or its pegylated forms (subcutaneous solution), or ruxolitinib (oral tablet). The study involves a randomized, open-label design where treatments are compared directly. Throughout the study, participants will be monitored for their hematologic response up to about 52 weeks. Assessments include platelet and neutrophil counts before starting treatment to ensure eligibility. Safety and efficacy are tracked to evaluate the long-term impact of the treatments on ET.

Researchers are evaluating the safety, tolerance, and effects of elritercept, alone and combined with the JAK inhibitor ruxolitinib, in adults with myelofibrosis (MF). This Phase 2 study aims to learn how elritercept impacts the signs and symptoms of MF, how the body processes the drug, and its effects on anemia and blood cell counts. Elritercept is an investigational protein designed to boost red blood cell and platelet production by blocking certain signals that suppress blood formation. Participants receive elritercept as a subcutaneous injection either alone or in combination with oral ruxolitinib tablets. The study includes different groups based on prior treatments: those previously treated with JAK inhibitors and those currently on ruxolitinib with insufficient disease control or side effects limiting dose. A specific group in Brazil includes participants with no prior JAK inhibitor treatment. The study monitors participants over about 8 years, including long-term extension periods. During the study, participants will be regularly assessed for side effects, blood cell levels, and overall health. Researchers will track adverse events and serious side effects from informed consent through 30 days after the last dose. Other evaluations include laboratory tests, symptom assessments, and pharmacokinetic analyses to understand how elritercept behaves in the body. Participants agree to follow all study procedures and return for follow-up visits throughout the study period.

Researchers are evaluating how roginolisib works when combined with ruxolitinib compared to standard treatment in adults with Myelofibrosis (MF) who have not responded well to JAK inhibitors. This Phase I/II open-label, single-arm multi-center study aims to assess the safety and tolerability of this combination treatment. The study plans to enroll about 26 adults over 18 years old with MF who have been on stable doses of ruxolitinib for at least 3 months but have shown less than 25% spleen reduction and persistent symptoms. Participants will receive roginolisib (80 mg, corresponding to 72 mg roginolisib) along with ruxolitinib up to 25 mg twice daily. The study has two parts: initially 13 patients will be treated to evaluate the safety and benefit-risk profile, followed by another 13 patients to further assess these aspects. Treatment cycles are 28 days long, with treatment expected to continue for up to 52 weeks. During the study, participants will have regular assessments including monitoring for treatment-emergent adverse events, abnormal ECGs, laboratory parameters, and blood pressure changes at specified days within each treatment cycle. Assessments occur on Day 1 and 15 of the first cycle and Day 1 of subsequent cycles. Safety, symptom scores, and physical exams including spleen size will be closely followed. The total participation duration may last up to 52 weeks while on treatment.

Researchers are evaluating how well elritercept works compared to epoetin alfa in treating 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 see if elritercept can reduce the need for RBC transfusions, improve tiredness without transfusions, lower transfusion burden, and enhance quality of life. It also examines the immune response to elritercept and monitors its safety. Participants receive either elritercept or epoetin alfa as subcutaneous injections. The study is a phase 3, multicenter, randomized trial comparing the efficacy and safety of these two drugs. The treatment period lasts through 24 weeks, with each cycle lasting 28 days. Researchers monitor participants for RBC transfusion independence lasting at least 12 weeks and a significant increase in hemoglobin levels. During the study, participants undergo regular assessments including blood tests to measure hemoglobin and other blood counts. Researchers track transfusion needs and quality of life reports. Safety is carefully monitored throughout the trial. Participants are involved from screening through 24 weeks of treatment, with evaluations to measure the effectiveness of the treatments and any side effects.

The primary purpose of the study is to transition participants into an extension study to collect long-term safety and efficacy data. The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have shown the following criteria: * Participants from the IMG-7289-202/MK-3543-005 (NCT05223920) study must have received at least 6 months of treatment with bomedemstat; * Essential thrombocythemia (ET) and polycythemia vera (PV) participants from studies other than IMG-7289-202/MK-3543-005 must have achieved confirmed hematologic remission. No hypothesis testing will be conducted in this study.

Researchers are evaluating the effectiveness and safety of bomedemstat compared to hydroxyurea in people diagnosed with essential thrombocythemia (ET) who have not yet received cytoreductive therapy but need it. This Phase 3 study aims to determine if bomedemstat leads to a better lasting clinicohematologic response than hydroxyurea in these patients. Participants will receive either oral bomedemstat capsules or oral hydroxyurea capsules, with placebos used to maintain the study's double-blind design. The study compares these two treatments to see which better manages ET with a focus on sustained treatment response. The treatments are taken as capsules, but specific dosing schedules are not detailed in the available information. During the study, researchers will monitor participants up to 52 weeks to measure their durable clinicohematologic response. Participants will undergo regular assessments to evaluate treatment effects and safety. The study includes safety monitoring and collects data on how well patients respond to the therapies over time, ensuring comprehensive evaluation of both treatments.

Researchers are evaluating the optimal duration of antibiotic treatment for adults with complicated intra-abdominal infections (cIAI). This Phase 3 trial aims to compare a fixed extended duration of 28 days of antibiotics to the current standard care durations, which typically range from 7 to 18 days. The study will assess clinical outcomes, quality of life, and cost effectiveness over a 180-day follow-up period to determine which approach may better reduce treatment failure and improve patient care while considering antimicrobial resistance concerns. Participants will be randomly assigned to one of two groups: the standard care group, where antibiotic type and duration are determined by their clinician, or the fixed extended-duration group, which receives antibiotics for a set 28-day period. The study includes a total of 1166 adult patients recruited from intensive care units and hospital wards across approximately 30 NHS trust hospitals. The treatment period is followed by monitoring up to 180 days after randomization. During the study, patients or their personal consultees will complete quality of life questionnaires at baseline and at 30, 60, and 180 days post-randomization. They will also provide information about antibiotic use and healthcare resource utilization. Researchers will collect hospital records on admissions, relapses, and further infections. The main outcome measured is treatment failure within 180 days of randomization, with safety and effectiveness assessed throughout the follow-up period.

Researchers are evaluating a range of treatments to improve outcomes for adults admitted to intensive care units (ICUs) with severe community-acquired pneumonia (CAP), including cases caused by influenza and COVID-19. This Phase 3 adaptive platform trial, REMAP-CAP, is designed to test multiple treatment strategies simultaneously and adapt over time, allowing new treatments to be added as questions are answered. The trial also serves as a platform to quickly evaluate treatments during respiratory pandemics, such as COVID-19, through a sub-study called REMAP-COVID in the United States. Participants receive various interventions including antibiotics like ceftriaxone, moxifloxacin, or piperacillin-tazobactam, as well as macrolide therapies given for different durations. Other treatments assessed include corticosteroids such as hydrocortisone and dexamethasone, antiviral agents like oseltamivir and remdesivir, immune modulators including tocilizumab and baricitinib, and supportive care strategies such as mechanical ventilation methods. Dosing and duration vary for each treatment, with some interventions now closed. Treatments are administered according to local guidelines and clinical decisions, with some requiring intravenous or enteral routes. Participants are closely monitored with assessments focusing on survival and organ support status in the ICU up to 90 days after enrollment. The main outcomes measured include all-cause mortality by day 90 and the number of days alive without needing organ support in the ICU by day 21. The study collects data continuously to adapt treatment assignments for new participants, aiming to identify the most effective therapies. Follow-up and safety monitoring continue throughout hospitalization and up to 90 days after admission.

Researchers are evaluating whether adding navtemadlin to ruxolitinib treatment provides more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have not responded well to ruxolitinib alone. This Phase 3, randomized, double-blind study focuses on patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis. Participants must be JAK inhibitor-naive and have a suboptimal response to ruxolitinib treatment during the initial run-in period. During the study, all subjects start by receiving ruxolitinib alone in a run-in period. Those showing a suboptimal response are then randomly assigned in a 2:1 ratio to receive either navtemadlin or a navtemadlin placebo as an add-on to their ongoing ruxolitinib treatment. The study is blinded, so neither the participants nor the doctors know who is receiving the navtemadlin or placebo. Navtemadlin is an investigational MDM2 inhibitor, while ruxolitinib is a janus kinase 1/2 inhibitor. Participants are involved in assessments to compare spleen volume reduction and total symptom score reduction between the two treatment groups over 24 weeks. Researchers monitor safety and efficacy through clinical evaluations, symptom tracking, and laboratory tests. The study includes screening for performance status, blast counts, and TP53 wild-type status, ensuring participants meet specific health criteria before randomization.

Researchers are evaluating the effectiveness and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera (PV) who have the JAK2V617F mutation. PV is a chronic condition that increases the risk of blood clots and can progress to more severe diseases like myelofibrosis or leukemia. High-risk patients are those aged 60 or older or those with a history of blood clots. Current treatments often do not fully control symptoms or long-term risks in these patients. The study involves two treatment groups receiving oral medications: givinostat or hydroxyurea. Dosages of both drugs are adjusted based on side effects or how well the treatment is working, aiming for an optimal dose. The core treatment phase is a pivotal phase 3 trial designed to show whether givinostat is more effective than hydroxyurea. Patients who finish this phase may continue receiving givinostat in an extended treatment phase to collect additional long-term safety and efficacy data. Participants will be assessed regularly, including monitoring blood counts and clinical response up to week 48. The main outcome measured is the proportion of patients who achieve a response by week 48, evaluated between weeks 25 and 48. Safety monitoring includes heart rhythm checks and other clinical evaluations. Eligible patients must meet specific criteria related to diagnosis, risk factors, and treatment needs, and those who complete the core phase successfully may enter the extended phase for further observation.