Edinburgh

Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Researchers are studying a treatment called MK-2214 to see if it can slow certain brain changes in people with early Alzheimer's disease (AD). AD is a form of dementia that causes memory loss, difficulties with communication, and challenges in decision-making, which affect daily activities. The study aims to find out if MK-2214 can slow the spread of tau protein in the brain compared to a placebo and to assess the safety and tolerability of MK-2214. Participants will receive either MK-2214 or a placebo through an intravenous (IV) infusion. The study is designed as a phase 2, randomized, placebo-controlled, double-blind trial with parallel groups. The treatment period lasts up to about 23 months, during which participants will receive infusions as scheduled. The placebo looks like the study treatment but contains no active drug, helping researchers understand the treatment's effects. Throughout the study, participants will be monitored for changes in tau protein levels in the brain using PET scans and for any adverse events or side effects. Researchers will track the number of participants experiencing adverse events and those who stop treatment because of them, with safety follow-up lasting up to approximately 26 months. Participants will also undergo brain imaging such as CT, PET, or MRI scans. The study involves regular assessments to measure the treatment's impact and ensure participant safety over the study duration.

Researchers are investigating treatments for women with recurrent endometrial cancer that expresses different levels of the HER2 protein. The study has two groups based on the tumor's HER2 score: Cohort 1 includes patients with HER2 IHC 1+ or 2+ who have previously received immune checkpoint inhibitors and platinum-based chemotherapy, while Cohort 2 includes patients with HER2 IHC 3+. The purpose is to compare the effectiveness and safety of the investigational drug BNT323 (also called DB-1303) against chemotherapy in Cohort 1 and to evaluate BNT323 alone in Cohort 2. The study also looks at how the drug affects the immune system, the body's handling of the drug, quality of life, and potential side effects. Participants in Cohort 1 are randomly assigned to receive either BNT323 via intravenous infusion or a chemotherapy drug chosen by the investigator (doxorubicin, paclitaxel, or docetaxel if paclitaxel is unsuitable). Treatment continues until the cancer progresses, unacceptable side effects occur, or the participant withdraws consent. Those in Cohort 2 receive BNT323 alone until disease progression or other discontinuation criteria are met. The study includes a screening period, a treatment period expected to last about six months, followed by safety monitoring, efficacy follow-up, and long-term survival follow-up lasting up to approximately 53 months. During the study, participants undergo regular assessments including imaging scans to measure tumor response by RECIST criteria, safety monitoring for adverse effects, and evaluations of quality of life. Researchers also study the pharmacokinetics of BNT323 and the immune response. The main outcomes measured are progression-free survival in Cohort 1 and objective response rate in Cohort 2. Safety follow-up ensures ongoing monitoring after treatment to evaluate longer-term effects and participant wellbeing.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 with early symptoms of Alzheimer's disease, ranging from mild cognitive impairment to mild dementia. This Phase III clinical trial focuses on those who show evidence of Alzheimer's pathology and have a recent history of cognitive decline. The study aims to measure changes in cognitive function over 72 weeks. Participants will be randomly assigned to receive either intravenous trontinemab or a placebo. The trial is designed as a double-blind, placebo-controlled study, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts up to 72 weeks, during which participants will undergo various assessments to monitor their cognitive status and safety. During the study, participants will complete clinical tests including cognitive assessments and imaging such as MRI, PET scans, or cerebrospinal fluid analysis to confirm Alzheimer's pathology. A study partner will assist participants as needed. Researchers will track changes from the start of the study through week 72 using tools like the Clinical Dementia Rating. Safety monitoring and adherence to study procedures will also be closely observed throughout the trial.

Researchers are evaluating the safety and potential benefits of VHB937 in people aged 50 to 85 years with early Alzheimer's disease, including those diagnosed with Mild Cognitive Impairment due to Alzheimer's or mild Alzheimer's disease. This Phase II, multicenter, randomized, double-blind, placebo-controlled study aims to assess how VHB937 affects memory, thinking abilities, daily activities, and brain changes, while also studying how the body processes and responds to the treatment. The study includes an initial 72-week double-blind phase followed by an extension period. Participants will receive either VHB937 solution for infusion or a placebo solution through infusion during the 72-week double-blind phase. The study compares these two groups to evaluate the effects and safety of VHB937 in early Alzheimer's disease. After the double-blind phase, participants may continue in an extension period for further observation. Treatment involves regular infusions under controlled conditions throughout the study. During the study, participants and their study partners will attend visits for assessments including memory and cognitive tests, evaluations of daily functioning, brain imaging, and biomarker analysis from cerebrospinal fluid or PET scans. Researchers will monitor safety, record any side effects, and track changes using the Clinical Dementia Rating scale (CDR) over 72 weeks. The study requires a reliable partner to accompany participants to visits, and overall participation includes monitoring during treatment and the extension phase to thoroughly assess VHB937's effects and safety.

Researchers are investigating BGB-16673, a targeted protein degrader aimed at treating various B-cell cancers including marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, Waldenström macroglobulinemia, and diffuse large B-cell lymphoma. The study includes both Phase 1 and Phase 2 parts to determine safe and effective dosing and to evaluate the drug's response in patients. The trial is conducted under the new company name BeOne Medicines, previously known as BeiGene. The treatment involves oral administration of BGB-16673. Phase 1 focuses on dose escalation and safety expansion to identify the maximum tolerated dose and recommended dose for expansion over approximately 28 days to 3 years. Phase 2 includes expansion cohorts to assess overall response rates over about 3 years. Participants may have prior treatments including Bruton tyrosine kinase inhibitors and other anticancer therapies depending on their cancer type and study phase. Participants will be monitored closely with assessments of adverse events from the first dose until 30 days after the last dose or before starting new therapy, whichever comes first, for up to 47 weeks. The study measures tolerability, dosing recommendations, and treatment response. Eligibility assessments include performance status and measurable disease, with safety and response evaluations continuing through both phases for up to three years.

Researchers are evaluating the long-term safety and effects of nerandomilast in people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) who have previously completed treatment with nerandomilast in earlier studies. The study aims to understand how well participants tolerate nerandomilast over time, and whether it helps improve lung function, delays symptom worsening, reduces hospital visits, or impacts survival. This is a Phase 3 open-label extension trial. Participants take nerandomilast tablets daily for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study follows an open-label design where all participants receive nerandomilast. There are no placebo or comparator groups in this extension phase. Throughout the study, participants regularly visit their doctors for health assessments and lung function tests. Doctors monitor any health problems or side effects experienced during treatment. The main outcome measured is whether participants experience any adverse events up to the final follow-up visit, which occurs at week 99. This close monitoring helps evaluate the long-term safety and potential benefits of nerandomilast in this patient group.

Researchers are evaluating the safety and effectiveness of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as initial treatments for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC) whose tumors express PD-L1. This Phase III, randomized, double-blind, global study focuses on patients whose tumors meet the PD-L1 expression threshold of 1% or higher and do not have certain genetic mutations or rearrangements that would require other targeted therapies. Participants receive either rilvegostomig or pembrolizumab intravenously on the first day of each 21-day treatment cycle. Both groups also receive platinum-based chemotherapy drugs such as carboplatin or cisplatin, administered intravenously up to four cycles, along with pemetrexed given intravenously on Day 1 of each cycle. The study monitors these treatments as first-line therapy for metastatic non-squamous NSCLC. During the study, participants undergo regular assessments including imaging scans to measure tumor size and response, as well as evaluations of organ and bone marrow function. Researchers track overall survival and progression-free survival for up to approximately five years. Safety is closely monitored throughout, and patients are followed long-term to assess outcomes related to treatment effectiveness and tolerability.

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line (1L) treatment for patients with squamous metastatic non-small cell lung cancer (mNSCLC) whose tumors express PD-L1 (tumor cells (TC) ≥ 1%).

Researchers are evaluating the safety and effectiveness of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not worsened after definitive platinum-based concurrent chemoradiation therapy. This Phase III, randomized, double-blind, placebo-controlled, international study involves multiple centers. Participants receive intravenous infusions of durvalumab and domvanalimab or durvalumab and placebo. The treatments are given after patients have completed concurrent platinum-based chemotherapy and radiation therapy with a total radiation dose of approximately 60 Gy. The study monitors patients over time to assess treatment effects and safety. During the study, participants undergo evaluations including tumor tissue analysis for PD-L1 status, performance status assessments, and monitoring of organ and marrow function. The main outcome measured is progression-free survival up to 8 years after randomization. Researchers also monitor for any adverse effects and disease progression throughout the study period.