Stevenage

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab as first-line treatments for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have high PD-L1 expression. This Phase III, randomized, double-blind, and global study focuses on participants with stage IV mNSCLC who do not have certain genetic mutations or rearrangements and are eligible for systemic therapy. Participants receive either rilvegostomig or pembrolizumab intravenously on Day 1 of each 21-day cycle. The study compares these two biological treatments given as monotherapy. Both groups will be monitored over time to assess treatment impact and safety. Throughout the study, participants undergo evaluations including tumor measurements by CT or MRI, performance status assessments, and organ function tests. Researchers will measure overall survival and progression-free survival for up to approximately five years. Tumor samples are collected before treatment for central testing, and participants’ health and treatment responses are closely followed during the trial period.

Researchers are studying the effects of DMX-200 (repagermanium), a drug that blocks a receptor involved in inflammation, in people with focal segmental glomerulosclerosis (FSGS) who are also taking an angiotensin II receptor blocker (ARB). This Phase 3 trial aims to assess the safety and effectiveness of DMX-200 compared to placebo over 104 weeks in adults and adolescents aged 12 to 17 years. Following the initial study, an open-label extension will evaluate long-term safety and benefits for up to two more years. Participants will be randomly assigned to receive either DMX-200 at 120 mg twice daily or a placebo, while continuing their ARB treatment. The study includes a screening and qualification period lasting 6 to 14 weeks, a 104-week double-blind treatment phase, and a 4-week follow-up after treatment. Those completing this phase may enter the open-label extension for an additional minimum of 104 weeks, with another 4-week follow-up period, making the total study duration about 230 weeks. During the trial, participants will undergo regular assessments including urine protein and creatinine testing, kidney function monitoring by estimated glomerular filtration rate (eGFR), and safety evaluations. The main outcomes measured are changes in proteinuria, kidney function slope up to week 104, and long-term safety through week 216. Safety will be closely monitored throughout both the double-blind and extension periods to understand the drug's effects over time.

Researchers are comparing the length of time participants survive without signs of cancer returning after treatment for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). This Phase 3 study focuses on patients who have received Bacillus Calmette-Guérin (BCG) treatment and have specific FGFR mutations or fusions. The study aims to evaluate and compare disease-free survival between those treated with TAR-210 and those receiving intravesical chemotherapy chosen by the investigator. Participants will receive either TAR-210, a drug administered directly into the bladder, or one of two chemotherapy drugs, Mitomycin C or Gemcitabine, also given intravesically. All visible tumors must be fully removed before randomization. The study includes patients who are either unresponsive to BCG, experienced with BCG, or intolerant to BCG treatment. Participants must not be eligible for or must refuse radical cystectomy surgery. During the study, participants will be monitored for disease-free survival for up to five years. Researchers will perform assessments including urine testing, tumor tissue analysis, and biopsies as needed to confirm eligibility and monitor disease status. Safety, treatment adherence, and patient health status will be regularly evaluated to ensure ongoing suitability for the study.

Researchers are evaluating how a new blood thinner called asundexian affects the body's natural ability to dissolve blood clots, especially in patients with atrial fibrillation. This ability, known as endogenous fibrinolysis, is important because when it is impaired, the risk of dangerous clot-related events like heart attacks and strokes goes up. The study compares asundexian to apixaban, a commonly used blood thinner, to see which one better improves this natural clot-dissolving process. This study is linked to a larger clinical trial called OCEANIC-AF, which is testing these two drugs for safety and effectiveness.

Researchers are evaluating whether ziltivekimab can help people who were hospitalized due to a heart attack by potentially reducing the development of heart disease and preventing new heart attacks or strokes. This Phase 3 study compares ziltivekimab with a placebo, which is a dummy medicine that has no effect on the body. Both treatments are given by chance, with equal likelihood for participants to receive either ziltivekimab or placebo. Participants will inject the study medicine once a month under the skin in the stomach, thigh, or upper arm. Ziltivekimab is given as an initial loading dose followed by monthly maintenance doses. The placebo group receives a matching injection schedule. The study duration is about two years. During the study, researchers will monitor participants for the time until the first serious heart-related event, including cardiovascular death, non-fatal heart attack, or non-fatal stroke. Participants will be closely observed from the start of randomization up to 25 months. The study includes regular follow-ups to assess safety and effectiveness of the treatments throughout this period.

Researchers are studying how lipoprotein(a) levels in the blood affect the body's natural ability to dissolve blood clots, known as endogenous fibrinolysis. Elevated lipoprotein(a), or Lp(a), is linked to a higher risk of heart attack, stroke, and aortic valve disease. The study aims to see if there is a connection between raised Lp(a) levels and impaired fibrinolysis, and whether lowering Lp(a) with medications like PCSK9 inhibitors or inclisiran can improve this clot-dissolving process. Participants will undergo assessments including the Global Thrombosis Test and thromboelastography to measure blood clotting and fibrinolysis. Lp(a) levels will be measured using specialized immunoassays. For those eligible to receive PCSK9 inhibitors or inclisiran, these tests will be done before starting treatment and again 3 to 6 months afterward. Patients with moderate or severe aortic valve calcification will have these assessments once. During the study, participants will provide blood samples for analysis of clotting markers and inflammation. Researchers will monitor changes in thrombotic status and Lp(a) levels over 3 to 6 months. The study tracks how well natural clot breakdown improves with treatment and collects data to better understand cardiovascular risk related to Lp(a). Participants will be followed throughout the treatment period to evaluate safety and effectiveness of fibrinolysis changes.

Researchers are investigating the relationship between haemodiafiltration (HDF) convection volume and the clearance of middle molecules, specifically Beta 2-Microglobulin, in patients with end stage renal disease. HDF is a dialysis technique that combines diffusion and convection. Previous large trials have shown that high convection volume HDF may improve survival, but the exact reasons for this benefit are not fully understood. The study aims to explore how convection volume affects toxin removal and clinical parameters to potentially improve dialysis treatment prescriptions. This observational study will recruit about 400 adults who have been on haemodiafiltration for at least three months. Each participant will undergo a single routine dialysis session where clinical parameters and dialysis information, including convection volume, will be recorded. Blood tests will be taken before and after dialysis to measure the removal of middle molecules. The study will analyze how convection volume relates to the reduction ratio and serum concentration of Beta 2-Microglobulin. Participants will be involved in one observed dialysis session with standard care assessments and additional blood sampling. Researchers will monitor clinical parameters, dialysis convection volume, and toxin removal. The main outcomes include the relationship between HDF convection volume and Beta 2-Microglobulin clearance over 18 months. The findings may help simplify dialysis prescriptions and improve patient care by focusing on middle molecule clearance rather than solely on small molecule removal.

Researchers are evaluating whether avoiding further axillary treatment after neoadjuvant chemotherapy (NACT) is as effective as standard axillary treatment for patients with early stage breast cancer who initially had cancer in the lymph nodes confirmed by needle biopsy but show no residual cancer in the lymph nodes after NACT. The study aims to determine if skipping axillary lymph node dissection (ALND) or axillary radiotherapy (ART) affects disease free survival (DFS) and whether it reduces the risk of lymphoedema five years after treatment. This phase 3, open-label, randomized trial includes patients with T1-3N1M0 breast cancer and confirmed nodal metastases who have undergone sentinel node biopsy removing at least three lymph nodes post-NACT.

Haemodialysis is a crucial treatment for patients with End-Stage Renal Disease, requiring repeated needling of arteriovenous fistulas or grafts to maintain vascular access. This procedure is often painful and emotionally challenging for patients. Healthcare professionals (registered nurses and healthcare assistants) who perform needling face significant job-related stress and emotional demands, impacting their well-being and patient care. The study aims to explore these healthcare professionals' experiences and views on needling to identify improvement areas and inform training programs that enhance the patient needling experience. This research will use a qualitative exploratory design involving semi-structured interviews with 12 to 16 registered nurses and healthcare assistants working in renal dialysis units at East and North Hertfordshire NHS Trust, including both main and satellite units. The study focuses on gathering detailed insights about the technical challenges, communication barriers, and patient-related factors influencing the needling process. Data analysis will use thematic methods to identify key themes from interview transcripts. The study will run over 10 months. Participants will share their needling experiences and perspectives through interviews, helping researchers understand the difficulties and emotional aspects of the procedure. The study will assess healthcare professionals' views on technical skills and patient interactions to guide targeted training efforts. The primary outcome is to gather insights on the needling experience by March 2024, aiming to improve support systems and enhance overall patient care during haemodialysis.