Stevenage

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

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 DMX-200 repagermanium, a drug that blocks a receptor involved in inflammation, in patients with focal segmental glomerulosclerosis FSGS who are also receiving an angiotensin II receptor blocker ARB. This Phase 3 study aims to assess the safety and effectiveness of DMX-200 compared to placebo over two years in adults and adolescents aged 12 to 17 years. The study is led by Dimerix Bioscience Pty Ltd and includes a double-blind period followed by an open-label extension to observe long-term effects. Participants receive either 120 mg of DMX-200 or a matching placebo capsule twice daily for 104 weeks during the double-blind treatment phase. Afterward, those who complete this phase may enter a two-year open-label extension where all participants receive DMX-200 twice daily. The study includes a screening and qualification period lasting 6 to 14 weeks, a possible titration phase, a stabilization phase, and a follow-up period after treatments. Throughout the trial, patients will undergo assessments including urine proteincreatinine ratio and kidney function tests like estimated glomerular filtration rate eGFR at multiple time points up to week 104 and during the extension. Safety and tolerability are closely monitored through regular evaluations, adverse event tracking, and follow-up visits. Total participation may last about 230 weeks, covering all study phases and follow-up periods.

Researchers are evaluating the disease-free survival in participants with high-risk non-muscle-invasive bladder cancer HR-NMIBC who have previously received Bacillus Calmette-Gurin BCG treatment. This Phase 3 trial compares a new treatment called TAR-210 with the investigators choice of intravesical chemotherapy. The study focuses on participants with specific fibroblast growth factor receptor FGFR alterations and aims to find out which treatment better prevents cancer recurrence or progression after BCG therapy. Participants are randomly assigned to one of two groups. Group A will have TAR-210 inserted into the bladder starting on Day 1 and continuing for about 2 years. Group B will receive either mitomycin C or gemcitabine chemotherapy, chosen by the investigator, given once weekly for 4 to 6 weeks induction, followed by monthly maintenance doses for up to 1 year, with a possible second year of maintenance at the investigators discretion. All treatments are delivered directly into the bladder intravesically. During the study, participants will be monitored for up to 5 years to track disease-free survival and other outcomes such as recurrence-free survival, time to next intervention, disease worsening, progression, and overall survival. Researchers will also assess side effects, laboratory and vital sign changes, and quality of life using specific questionnaires. The study includes regular evaluations and safety monitoring throughout the participation period, which may last several years.

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.

This observational study focuses on patients with end stage kidney disease ESKD undergoing haemodialysis HD or haemodiafiltration HDF. It aims to understand differences in middle molecules clearance and patient outcomes between high 23 Litres and low <23 Litres convection volume HDF treatments. The study also evaluates how dialysate fluid sodium concentration 137 vs 140 mmolL affects overhydration volume in patients receiving HD and HDF. Participants are observed in groups based on their treatment type those receiving high or low convection volume HDF and those dialysing with different dialysate sodium concentrations 137 or 140 mmolL. No additional interventions are administered, as this study monitors routine dialysis treatments to assess toxin clearance, fluid status, and sodium balance in real-world settings. Participants will be monitored for 12 months to assess the effect of convection volume and dialysate sodium concentration on middle molecules clearance and patient-reported outcomes such as fatigue and recovery time. Long-term follow-up over 5 years will examine the relationship between middle molecule clearance and major cardiovascular events and hospitalizations. Data collection includes clinical evaluations, patient questionnaires, fluid status measurements, and biochemical markers to comprehensively assess dialysis adequacy and patient health.

Researchers are investigating how a new blood thinner called asundexian affects the bodys natural ability to dissolve blood clots, known as endogenous fibrinolysis, in patients with atrial fibrillation. This study compares asundexian to apixaban, a commonly used anticoagulant, to see which better improves clot breakdown. This linked observational study builds on the main OCEANIC-AF trial, aiming to reduce risks of heart attack and stroke by targeting impaired clot dissolving mechanisms. Participants are already enrolled in the OCEANIC-AF trial and will have four additional blood samples taken to assess clotting status. Blood samples are collected before starting the study drug and then at 3, 6, and 12 months. The study uses specialized tests like the Global Thrombosis Test and Thromboelastography to evaluate platelet activity, clot formation, and fibrinolysis time, along with various blood markers related to thrombosis. During the study, researchers will monitor thrombotic status over 12 months by analyzing these blood samples. Participants will provide informed consent and agree to blood draws at scheduled visits. The main measurement is how well the body dissolves clots, which may help guide future treatments for atrial fibrillation patients with impaired fibrinolysis.

Researchers are evaluating ziltivekimab, a new medicine not yet approved anywhere, to see if it can help people who were hospitalized due to a heart attack. The study aims to find out if ziltivekimab can reduce the development of heart disease and prevent future heart attacks or strokes. This is a Phase 3 clinical trial comparing ziltivekimab to a placebo in patients with acute myocardial infarction. Participants will receive an initial loading dose of ziltivekimab or matching placebo by injection under the skin as soon as possible after an invasive heart procedure, within 36 hours for STEMI or 48 hours for NSTEMI patients. After the loading dose, they will get monthly injections of the same study medicine for up to two years, in addition to their standard care. During the study, participants will be monitored for major cardiovascular events such as heart attack, stroke, and cardiovascular death. Researchers will also track other heart-related outcomes and safety measures over a period of up to 25 months. The study involves regular visits for injections, assessments, and laboratory tests to evaluate the medicines effects and patient health throughout the trial.

Researchers are investigating the relationship between lipoproteina Lpa levels in the blood and the bodys natural ability to dissolve blood clots, called endogenous fibrinolysis. This study focuses on patients with atherosclerotic cardiovascular disease or aortic valve disease, aiming to understand if reducing Lpa with medications like PCSK9 inhibitors or inclisiran can improve clot dissolution and potentially lower the risk of heart attacks and strokes. Elevated Lpa is considered a risk factor that may impair fibrinolysis, and new cholesterol-lowering treatments have shown promise in reducing these levels. The study involves assessing patients who are eligible for treatment with PCSK9 inhibitors or inclisiran and those diagnosed with moderate or severe aortic valve calcification. Blood clotting and fibrinolysis will be measured using specialized tests such as the Global Thrombosis Test and thromboelastography. Lpa levels will be measured through immunoassays. Assessments will occur before starting treatment and again 3 to 6 months after treatment initiation for those receiving therapy. Patients with aortic valve calcification will be assessed once. During participation, blood samples will be collected to analyze clotting and fibrinolysis markers, as well as Lpa levels. The study will review thrombotic status and Lpa levels at 3 to 6 months to evaluate changes. This observational study involves monitoring without altering usual care. The total duration of involvement varies, depending on treatment eligibility and follow-up timing. The research is sponsored by the East and North Hertfordshire NHS Trust to better understand clotting risks and treatment responses in cardiovascular patients.

Researchers are studying patients with aortic valve disease who are undergoing either surgical aortic valve replacement SAVR or transcatheter aortic valve implantation TAVI to understand the risk of thrombosis and related complications. This observational study aims to use novel blood biomarkers to assess clotting and clot breakdown, identifying patients at risk for valve thrombosis and related adverse events such as stroke, systemic embolism, and valve failure. The study also seeks to determine the time periods when the risk of valve thrombosis is highest. Participants will have blood tests at several time points to measure thrombosis and thrombolysis markers, which may be influenced by their prescribed blood-thinning medications. They will be monitored using 4D CT scans, echocardiography, and clinical reviews to detect adverse events including major cardiac and cerebrovascular events, valve thrombosis, bleeding, and new or worsening atrial fibrillation. These evaluations will continue regularly over a five-year follow-up period. Throughout the study, participants will provide blood samples and undergo imaging and clinical assessments to track their health and valve function. Researchers will closely observe clinical outcomes such as major cardiac events, strokes, systemic embolism, and bleeding over the five years. This long-term monitoring helps identify when patients face the greatest risks and how well blood tests predict these complications, supporting safer, targeted treatment approaches.