Sunderland

This research aims to evaluate the effectiveness and safety of two different dose schedules of pegozafermin compared to a placebo in adults with metabolic dysfunction-associated steatohepatitis (MASH) who have liver fibrosis at stage F2 or F3. This phase 3 study focuses on improving liver fibrosis and steatohepatitis in this patient group, which involves chronic liver disease associated with metabolic dysfunction. Participants will receive either pegozafermin or a placebo through subcutaneous injections. The study compares two doses of pegozafermin to assess their impact on liver fibrosis and steatohepatitis. The treatment period lasts up to 52 weeks, with outcomes measured at this time point. During the study, participants will be monitored for improvements in liver fibrosis and resolution of steatohepatitis without worsening fibrosis by week 52. Researchers will also track the time until any disease progression occurs, up to 5 years. Throughout the trial, safety and efficacy will be carefully assessed through clinical evaluations and laboratory tests to ensure participant well-being.

Researchers are evaluating how well elritercept (TAK-226, KER-050) works in reducing the need for red blood cell (RBC) transfusions in adults with very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require regular blood transfusions. The study is a Phase 3, double-blind, randomized, placebo-controlled trial that also aims to assess the safety and tolerability of elritercept over both short and longer periods, including in adults with high transfusion needs. Participants will be randomly assigned in a 2:1 ratio to receive either elritercept or a matching placebo by subcutaneous injection every 4 weeks. The study includes a Primary Phase lasting 24 weeks and a Secondary Phase lasting an additional 24 weeks, during which participants continue the same treatment. Following these phases, an Extension Phase allows eligible participants to continue treatment until discontinuation or study unblinding. Study visits occur every 2 weeks during the first 6 cycles and every 4 weeks thereafter. Treatment continuation depends on meeting disease assessment criteria every 24 weeks. Participants will undergo various assessments including bone marrow aspirates, transfusion evaluations, and disease status checks throughout the study. Safety follow-up lasts for 8 weeks after the last dose, with visits every 4 weeks during this time. Afterward, long-term follow-up occurs quarterly for up to 5 years or until withdrawal, death, loss to follow-up, or study closure. The main outcome measured is the percentage of participants achieving transfusion independence for at least 8 weeks during the first 24 weeks of treatment.

Researchers are evaluating adults aged 18 and older who have a specific eye condition called centre-involved diabetic macular edema (CI-DME), a type of diabetic macular edema. The study aims to find out whether an oral medicine called BI 1815368 can improve vision in people with CI-DME and to determine the best dose. This is a Phase 2 study focused on assessing the medicine's safety, efficacy, and tolerability over 48 weeks of treatment. The study has two parts. In the first part, participants are randomly assigned to one of two equal groups: one group takes BI 1815368 tablets and the other takes placebo tablets, which look like the medicine but contain no active drug. In the second part, participants are randomized into four groups of equal size, three of which receive different daily doses of BI 1815368, while one group continues to take placebo. All participants take tablets twice daily for about 11 months. Participants stay in the study for about a year and visit the study site 16 times. During visits, doctors check vision and collect detailed eye pictures along with health information. Researchers compare changes in vision and eye condition over time between the groups. The main outcome measured is whether participants gain 10 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters of visual acuity at week 48 compared to baseline, indicating improved sight.

Severe diabetic macular oedema (DMO) is a condition where fluid builds up in the macula, the central part of the retina responsible for detailed vision, leading to sight loss. This trial studies people over 18 years old with type 1 or type 2 diabetes who have severe DMO, defined by a thickened macula (400 microns or more). Researchers are comparing the current standard treatment of anti-VEGF eye injections alone to a new approach where patients start with anti-VEGF injections and switch to subthreshold micropulse laser (SML) treatment once the macula thickness decreases below 400 microns. Participants will be randomly assigned to receive either ongoing anti-VEGF injections or to switch to SML treatment after initial anti-VEGF therapy. Anti-VEGFs such as ranibizumab, aflibercept, faricimab, and brolucizumab are given as monthly injections at first, then every 1-3 months. The SML procedure, which does not damage the macula, will be applied based on the trial guidelines once the macula is less than 400 microns thick. This study aims to see if the combined treatment is as effective and more cost-efficient than anti-VEGF injections alone. Participants will attend regular clinic visits for eye exams including optical coherence tomography (OCT) scans to measure macula thickness and assessments of visual acuity over 104 weeks after randomization. Researchers will monitor best-corrected visual acuity, side effects, participant experience, and cost-effectiveness. The trial includes follow-up for two years with safety monitoring and evaluation of how this approach might be adopted in routine care. The study is conducted at multiple hospital eye services across the UK.

Alport syndrome (AS) is a rare genetic disorder caused by changes in specific genes that produce collagen, leading to kidney disease, hearing loss, and eye abnormalities. People with AS are at high risk of developing chronic kidney disease, where the kidneys gradually lose their function, often marked by excess protein in the urine called proteinuria. This study focuses on evaluating BAY 3401016, a monoclonal antibody designed to block the protein Semaphorin 3A, which may contribute to kidney damage in AS, aiming to slow kidney function loss in adults with rapidly progressing AS. Participants will receive either BAY 3401016 or a placebo in a randomized, double-blind, parallel group Phase 2a study. The study includes an extension phase to further assess the treatment's effects. The treatment duration covers at least 24 weeks with follow-up visits extending up to 90 days after the end of treatment. The study measures the urinary albumin creatinine ratio (UACR) over weeks 16, 20, and 24 to evaluate kidney function. During the study, participants will undergo regular assessments including kidney function tests and urine measurements to monitor protein levels. Safety and efficacy will be tracked throughout treatment and follow-up. The study includes adults aged 18 to 45 with specific criteria related to kidney function and proteinuria levels. Overall participation spans the treatment period plus a 90-day post-treatment follow-up, with researchers closely observing changes in kidney health and safety outcomes.

Researchers are evaluating treatment options for patients with early-stage classical Hodgkin lymphoma who have not received prior therapy. This international phase III trial runs two parallel studies in different regions, combining data to better understand treatment effects. The trial compares two chemotherapy regimens, ABVD and A2VD, with treatment adapted based on PET-CT scan results after two cycles to guide further therapy. Participants will be randomly assigned to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine, and dacarbazine with growth factor support). PET-CT scans are performed after one cycle for exploratory purposes and after two cycles to determine subsequent treatment. Depending on PET results, patients may receive additional chemotherapy cycles or involved site radiotherapy following ILROG guidelines. Those with poor response discontinue trial treatment and receive alternative therapy. During the study, patients undergo PET-CT scans and regular assessments to monitor treatment response and safety. Follow-up continues for at least five years after treatment completion to assess progression-free survival. Researchers collect clinical data and imaging results to evaluate outcomes, with central review of PET scans guiding treatment adaptations. Participants are monitored for side effects and overall health throughout the trial period.

Over 18 million adults in the United Kingdom experience significant hearing loss, which is associated with social isolation, depression, and other health conditions. Hearing aids are the main treatment option, but many users either do not use them or use them irregularly, reducing their benefits and increasing healthcare costs. This study aims to test an NHS-endorsed text-messaging system called Florence to support new hearing aid users, focusing on improving adherence, outcomes, and cost-effectiveness through a feasibility trial with proof-of-concept and process evaluation. The study uses a standardized audiology text-message protocol delivered through Florence, designed to prepare, inform, and support new NHS hearing aid users as they receive and start using their hearing aids. This behavioral intervention will be tested in adults aged 18 years and older who are prescribed their first NHS acoustic hearing aids for hearing loss. Participants will receive messages to help them manage their hearing aids between appointments. Participants will be monitored from enrollment through weeks 16 and 28, reporting their hearing aid use and completing the Glasgow Hearing Aid Benefit Profile at specified times. The study will assess the feasibility of the trial, the effectiveness of the text messaging in improving hearing aid use, and gather feedback on the process. This evaluation aims to enhance hearing aid adherence, improve quality of life, and reduce NHS costs over time.

Researchers are evaluating the long-term safety and tolerability of the Port Delivery System with ranibizumab (PDS) at 100 mg/mL in people with neovascular age-related macular degeneration (nAMD). This study includes participants who have completed previous Phase II or Phase III studies or reached Week 24 in a related study but were not randomized. The study also explores two sub-studies: one assessing a laser treatment to reduce eye bleeding related to the PDS implant procedure, and another assessing the safety of re-implanting an updated PDS device. Participants receive the PDS implant with ranibizumab according to specific schedules in their study arms. The first sub-study uses transscleral photocoagulation with an Iridex laser system to reduce vitreous hemorrhages after implantation, enrolling about 55 participants. The second sub-study involves up to 100 participants in the United States who undergo re-implantation of the updated device and are followed for up to 72 weeks. Treatments and procedures are carefully monitored throughout. Participants undergo regular visits for up to 240 weeks to monitor for adverse events, including eye-related and systemic effects, severity, duration, and any device-related issues. The sub-studies also track specific complications like vitreous hemorrhages and adverse device effects during postoperative and follow-up periods. Safety assessments include eye exams, imaging, and evaluation of systemic health to ensure ongoing monitoring of participant well-being throughout the study.

Researchers are studying patients with known or suspected angina who do not have obstructive coronary artery disease to see if a special diagnostic test can help guide personalized treatment. This condition includes ischaemic heart disease, microvascular angina, and vasospastic angina. The trial builds on earlier research suggesting that tailoring treatment based on coronary vascular function tests may improve symptoms and quality of life. This large, multicentre, blinded, randomized study aims to confirm these findings and assess effects on health and wellbeing over a longer period. Participants undergo invasive coronary angiography along with an adjunctive interventional diagnostic procedure (IDP) that measures coronary vascular function using a guidewire technique. Patients with no significant artery blockage are randomized into two groups: one where IDP results are disclosed to guide treatment decisions, and a control group with concealed results receiving standard care. Those with abnormal vascular function in the intervention group may have repeated assessments to tailor medications, such as calcium channel blockers. Patients with obstructive artery disease or other exclusions may join a registry for follow-up and assessment. Throughout the study, participants complete questionnaires about angina symptoms, quality of life, activity levels, treatment satisfaction, and pain. Researchers monitor clinical outcomes for at least 12 months, including major cardiovascular events. The study also evaluates the safety and usefulness of the diagnostic procedure in multiple hospitals across Europe. Blood samples are collected to explore disease mechanisms. Participants and their doctors remain blinded to group assignments, but diagnoses are shared to help guide care following current guidelines.

Researchers are evaluating two common treatments for idiopathic intracranial hypertension (IIH), a condition marked by increased pressure inside the skull that can cause headaches, blurred vision, and ringing in the ears. IIH primarily affects women of reproductive age with obesity and can lead to blindness if untreated. This trial compares cerebrospinal fluid (CSF) shunting and dural venous sinus stenting (DVSS) to determine which approach is more effective and cost-efficient in preserving vision. Participants will be randomly assigned to receive either CSF shunting, which involves implanting a thin tube to drain brain fluid, or DVSS, where a metallic stent is placed inside a brain blood vessel. The type of CSF shunt used may be ventriculoperitoneal or lumboperitoneal based on the medical team's decision, and the specific stent model is not fixed by the protocol. The study is conducted in NHS hospitals across England, Wales, and Scotland, with the intervention followed by regular monitoring and assessments. Over two years, participants will attend 11 hospital visits and one phone appointment to monitor vision changes, headaches, side effects, and device performance. Researchers will collect health data from NHS Digital and measure the retinal nerve fibre layer thickness using OCT scans at six months. The study began in July 2023, with the final patient visit expected in May 2028, aiming to provide clearer guidance on the best treatment to prevent sight loss in adults with IIH.