Lincoln

Researchers are evaluating treatments for germinal center B-cell-like diffuse large B-cell lymphoma GCB DLBCL, a fast-growing blood cancer affecting immature B-cells. The study compares two treatment combinations to see if more people respond to zilovertamab vedotin MK-2140 plus R-CHP versus polatuzumab vedotin plus R-CHP. This Phase 2 trial aims to assess the effectiveness and safety of these regimens in participants with newly diagnosed GCB DLBCL. Participants receive either zilovertamab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone R-CHP, or polatuzumab vedotin combined with R-CHP. Treatments are given by intravenous infusion on Day 1 of each 3-week cycle for up to 6 cycles, approximately 4 months, with prednisone or prednisolone taken orally for 5 days of each cycle. For participants with high-risk DLBCL, up to 2 additional cycles of rituximab or biosimilar are given. During the study, participants are monitored for response to treatment using Lugano Response Criteria, with follow-up lasting up to about 31 months for the primary outcome. Secondary outcomes include progression-free survival, overall survival, event-free survival, duration of complete response, adverse events, and quality of life assessments. Safety and health status are regularly checked through exams, lab tests, and questionnaires over several years, with total study participation extending up to 7 years.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

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 studying pirtobrutinib, an oral drug, to understand how well it works and how safe it is for people with chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL. The study focuses on participants who have previously received 1 to 3 treatments, including a covalent Bruton tyrosine kinase BTK inhibitor, as well as those with treatment-nafve CLLSLL who have a specific genetic change called 17p deletion. This is a Phase 2 open-label trial sponsored by Loxo Oncology, Inc. The study has two parts. Part 1 tests three different dose levels of pirtobrutinib in participants with relapsed or refractory CLLSLL who have prior treatment experience, lasting about 3 years. Part 2 evaluates pirtobrutinib alone in participants who have not received prior treatment but have the 17p deletion, with participation lasting up to 2 years. All doses are given orally. Participants will take the study drug orally and attend visits for up to 3 years in Part 1 or up to 2 years in Part 2. Researchers will monitor how well the disease responds to treatment using overall response rate and how long the response lasts. Safety will be tracked throughout. Participants ability to swallow oral medication and their overall health status will be assessed before and during the study to ensure suitability and safety.

Researchers are evaluating oral Nuvisertib TP-3654, a PIM inhibitor, in a Phase 12 open-label trial for patients with intermediate or high-risk primary or secondary myelofibrosis. The study aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Nuvisertib. Participants include those who have been previously treated with JAK inhibitors, those currently on ruxolitinib with suboptimal response, and patients treated with other JAK inhibitors except momelotinib. The trial includes three treatment arms Nuvisertib alone, Nuvisertib combined with ruxolitinib, and Nuvisertib combined with momelotinib. Patients will receive oral doses with dose escalation to determine safe and effective levels. Each arm enrolls specific patient groups based on prior treatments and response. The study monitors drug effects and interactions when used alone or in combination with other JAK inhibitors. Participants will be closely monitored for dose-limiting toxicities, adverse events, spleen volume reduction, symptom improvement, and other pharmacokinetic measures. Regular assessments include symptom scoring, imaging scans for spleen size, laboratory tests, and cardiac monitoring. The study duration and follow-up extend to evaluate both safety and preliminary activity, with careful tracking of treatment effects over time.

Researchers are evaluating how well elritercept works to improve anemia in adults with myelofibrosis MF who are already taking ruxolitinib. The study compares elritercept to a placebo and aims to see if elritercept can reduce tiredness, improve MF-related symptoms, and help participants perform physical activities more easily. It also looks at elritercepts effects on bone marrow, spleen size, antibody development, and long-term safety. Participants receive either elritercept or a placebo by subcutaneous injection once every 4 weeks during a 36-week double-blinded treatment period. The starting dose of elritercept is 3.75 mgkg, with a possible increase to 5.0 mgkg after the second cycle based on response and safety. After 36 weeks, participants who took placebo may switch to receive elritercept in an extended open-label phase. During the study, participants undergo assessments including blood transfusion independence, symptom and fatigue questionnaires, spleen imaging, and bone marrow evaluation. Researchers monitor safety, antibody formation, and survival for up to 7 years. The main outcome is the proportion of participants who become independent from red blood cell transfusions for at least 12 consecutive weeks during the 36-week treatment. Participants are involved in regular visits and evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the effectiveness of glofitamab alone compared to an investigators choice of treatments for adults with relapsed or refractory mantle cell lymphoma MCL. This phase III trial focuses on patients whose lymphoma has returned or not responded after previous treatments, including those who have received BTK inhibitors. The study aims to determine which treatment better controls the disease and improves patient outcomes. Participants in the glofitamab group will first receive two intravenous doses of obinutuzumab before starting glofitamab infusions every 21 days for up to 12 cycles. Those in the comparison group will receive either bendamustine plus rituximab for up to six 28-day cycles or rituximab combined with daily oral lenalidomide for 28-day cycles until their disease progresses. Tocilizumab may be given intravenously as needed to manage side effects like cytokine release syndrome. Throughout the study, participants will undergo regular assessments including scans to measure tumor size, blood tests, and quality of life questionnaires. The main measure is progression-free survival up to about 24 months, with additional evaluations of response rates, overall survival, symptom changes, and drug levels. Safety monitoring and long-term follow-up will occur during this period to track treatment effects and patient well-being.

This trial investigates adults aged 45 to 80 with elevated Lipoproteina Lpa levels, who either have existing cardiovascular disease or are at risk for a first cardiovascular event. The study aims to evaluate how lepodisiran, compared to a placebo, affects the amount and type of plaque in the coronary arteries using Coronary Computed Tomography Angiography CCTA. Lipoproteina is a protein carrying cholesterol and is linked to higher heart disease risk. Participants are randomly assigned to receive either lepodisiran or a placebo through subcutaneous injections. The study lasts about 120 weeks, with primary evaluation of changes in noncalcified plaque volume at baseline and at week 104. Secondary measures include changes in fat attenuation index scores, Lpa levels over time, participant feedback on drug administration, and pharmacokinetic analysis. Throughout the study, participants will undergo imaging assessments, blood tests to monitor Lpa levels, and questionnaires regarding treatment experience. The main outcome is the percent change in noncalcified plaque volume in heart vessels. The study includes safety monitoring and continues follow-up to assess effects comprehensively over the study period.

Researchers are evaluating two types of stereotactic body radiotherapy SBRT in men with high risk localized prostate cancer, where the cancer is confined to the prostate but may grow quickly or spread. The study aims to compare the safety and effectiveness of delivering radiotherapy to the prostate alone versus the prostate plus surrounding lymph nodes, with both treatments given in only 5 sessions. This phase III trial is designed to see if including lymph nodes reduces the chance of cancer returning and to review any side effects that occur. Participants will be randomly assigned to one of two groups. One group will receive SBRT targeting the prostate and seminal vesicles, delivering 36.25Gy in 5 fractions on alternate days with 40Gy to the prostate clinical target volume. The other group will get the same prostate treatment plus 25Gy in 5 fractions to the pelvic lymph nodes on alternate days. Treatments will be provided over approximately two weeks at experienced NHS radiotherapy centers that meet quality standards for these therapies. During the study, participants will be monitored for at least three and a half years to assess time to biochemical or clinical failure, which is the main outcome. Researchers will also track acute and late side effects, cancer relapse, survival rates, patient-reported outcomes, and adherence to treatment protocols for up to five years post-randomization. Regular imaging and assessments will be performed before treatment to confirm eligibility and exclude metastatic disease. Overall, participants can expect close monitoring and follow-up throughout and after their treatment period.

Researchers are evaluating whether tralokinumab given as subcutaneous injections along with topical corticosteroids TCS is safe and effective for treating moderate-to-severe atopic dermatitis AD in children and infants. The trial involves two age groups children aged 2 to under 12 years and infants aged 6 months to under 2 years. Children are randomized to receive either tralokinumab plus TCS or placebo plus TCS, while infants receive open-label tralokinumab plus TCS. This Phase 3 trial will last up to four years with visits every two weeks during the first year and every six weeks thereafter, including some phone visits.