Newcastle

Researchers are evaluating molnupiravir, a study medicine designed to stop the COVID-19 virus from multiplying, to see if it can prevent severe illness from COVID-19 more effectively than a placebo. This Phase 3 randomized, placebo-controlled, double-blind study focuses on non-hospitalized adults at high risk of severe disease progression due to COVID-19. The study addresses the need for alternative treatments for people who cannot take certain COVID-19 medications due to availability or potential drug interactions. Participants will receive either molnupiravir or a placebo, both given orally as two 400 mg film-coated tablets every 12 hours for 5 days, totaling 10 doses. Some participants may also receive remdesivir as part of standard care if clinically appropriate and available. The study compares the effects of molnupiravir with placebo in preventing severe illness outcomes. Throughout the study, participants will be monitored for outcomes such as hospitalization, death, or medically attended visits related to COVID-19 up to 29 days. Safety is assessed by tracking adverse events for up to about 5 months and discontinuation of study treatment due to adverse events for about 5 days. The study involves laboratory tests, symptom assessments, and safety evaluations to understand molnupiravir's impact on disease progression and participant health.

Researchers are evaluating the safety and performance of the Polymer Free Sirolimus Eluting Coronary Stent Vivo ISAR in patients with coronary artery disease (CAD). This prospective, observational registry includes patients who have undergone percutaneous coronary intervention (PCI) using this stent and are planned for a short dual antiplatelet therapy (DAPT) regimen lasting up to 3 months. The aim is to assess clinical outcomes in a real-world population across multiple countries and centers. Participants receive the Vivo ISAR stent and follow standard care with a short DAPT treatment of no more than 3 months after PCI. The study does not influence the choice of device or treatment beyond routine care. After the procedure, patients who meet eligibility criteria and provide consent are enrolled and observed over time without additional interventions. Participants will be followed up through routine clinical practice and telephone calls at 30 days, 3 months, and 12 months after PCI. These follow-ups collect information on ongoing medications, any lab tests performed, adverse events, and any further interventions. The main outcomes measured at 12 months include ischemic events and bleeding events related to the treatment and stent use.

Researchers are investigating whether using coronary CT angiography (CCTA) to guide calcium modification during percutaneous coronary intervention (PCI) can improve treatment outcomes for patients with significant calcified coronary artery disease. This study compares the CCTA-guided approach to the current standard of care, which uses intravascular ultrasound (IVUS) guidance. The goal is to see if the CT-based strategy can enhance procedural efficiency and stent results while maintaining similar clinical safety over 12 months. The study will enroll 700 patients with flow-limiting coronary artery stenosis and moderate-to-severe calcification. Participants will be randomly assigned to either a CCTA-guided calcium modification group or an IVUS-guided group. The CCTA-guided approach uses detailed CT imaging to plan the procedure and select plaque modification techniques before PCI, while the IVUS-guided strategy relies on intravascular ultrasound imaging during the procedure. Both groups will have their stent implantation confirmed by IVUS after the procedure. Participants will be monitored for procedural outcomes, including the final minimal stent area measured by IVUS, and clinical outcomes such as target vessel failure (cardiac death, heart attack, or need for revascularization) over 12 months. The study includes assessments of imaging quality, clinical safety, and effectiveness of the calcium modification strategies. Follow-up will ensure the safety and success of the interventions throughout the year after PCI.

Researchers are conducting a Phase I/II clinical trial to evaluate the safety, pharmacokinetics, and clinical activity of NUC-7738, a nucleotide analogue, in patients with advanced solid tumors and lymphoma. The study aims to determine the maximum tolerated dose (MTD) and dosing schedules of NUC-7738 alone and in combination with pembrolizumab. The trial includes patients with various cancers such as cutaneous melanoma and lymphoma, with particular focus on those who have progressed on prior therapies or have limited treatment options. In Phase I, NUC-7738 is administered intravenously as a monotherapy on either a weekly or fortnightly schedule in a dose-escalation design to assess safety and tolerability. Phase II involves dose-confirmation expansion cohorts where approximately 40 additional patients receive the selected dose and schedule of NUC-7738. Specific cohorts include patients with cutaneous melanoma receiving NUC-7738 alone or combined with pembrolizumab, and patients with lymphoma receiving NUC-7738 monotherapy. The combination cohort may expand based on efficacy signals. Participants undergo regular assessments including monitoring for dose-limiting toxicities, treatment-emergent adverse events, laboratory changes, physical exams, vital signs, and electrocardiograms from consent until 30 days after the last dose. Tumor response is evaluated every 8 weeks up to 22 months, measuring changes in tumor size, objective response rate, duration of response, disease control rate, duration of stable disease, and progression-free survival. The study may last up to approximately one year for Phase I and include long-term follow-up for tumor assessments in Phase II.

Researchers are evaluating the effectiveness of anitocabtagene autoleucel compared to standard of care therapy in adults with relapsed or refractory multiple myeloma who have previously received one to three treatments, including an anti-CD38 monoclonal antibody and an immunomodulatory drug. The study is a Phase 3, randomized, open-label trial aiming to assess how well anitocabtagene autoleucel works versus existing therapies in this patient group. Participants will receive either a single infusion of anitocabtagene autoleucel, which is a CAR+ transduced autologous T cell therapy, or one of several standard of care treatments. The standard treatments include combinations involving drugs such as pomalidomide, bortezomib, dexamethasone, daratumumab, carfilzomib, cyclophosphamide, and fludarabine, administered either orally or intravenously/subcutaneously. After the treatment period, those receiving anitocabtagene autoleucel will enter a follow-up phase and then transition to a long-term follow-up study lasting up to 15 years. During the study, participants will be monitored for progression-free survival for up to four years and for minimal residual disease complete response rate at nine months. Researchers will assess disease progression, treatment safety, and other health markers. Follow-up includes regular evaluations to track the participant's response and overall health status, with continued long-term monitoring planned for those treated with anitocabtagene autoleucel.

Researchers are evaluating the effects of filgotinib in children and adolescents aged 8 to less than 18 years with moderately to severely active ulcerative colitis (UC). The study aims to assess the drug's efficacy, safety, tolerability, and how the body processes the medication. About 80 participants, including at least 8 children aged 8 to under 12, will take part in this Phase 3 trial. Participants will receive filgotinib orally once daily in the morning, with or without food. The study drug is provided as film-coated tablets in doses appropriate for pediatric use, aiming for the same exposure level as adults receiving 200 mg daily. Participants will take the study drug at home on most days, but will take it under supervision at the study site during visits at Weeks 4, 10, and 22. Those not achieving remission or response by Week 10 will continue treatment until Week 22, after which those who still do not reach remission will stop treatment. During the study, participants will be closely monitored for treatment effects and safety. Researchers will assess remission and response at Weeks 10 and 58. Evaluations include clinical scoring of disease activity and safety assessments throughout the trial. Total participation duration and detailed monitoring plans are designed to understand both the short- and longer-term effects of filgotinib in this young population.

Researchers are observing the use of the drug elafibranor in people with Primary Biliary Cholangitis (PBC), a rare and progressive liver disease where bile ducts are damaged. This damage can lead to scarring of the liver (cirrhosis) and is often linked with symptoms like itching and fatigue. If PBC worsens, it may require a liver transplant or could be fatal without one. The study aims to understand how effective, safe, and tolerable elafibranor is for those being treated in everyday clinical settings. Participants in this study will be those who have been diagnosed with PBC and are either starting or already receiving treatment with commercial elafibranor at a dose of 80 mg per day. The study is non-interventional, meaning it observes participants as they receive their usual care without altering treatment. The total study duration for each participant is approximately 60 months, or 5 years. During the study, researchers will gather information about participants’ responses to treatment, safety, and tolerability over time. Outcome measurements include the percentage of participants who respond to treatment after 6 months. Participants and their caregivers may complete questionnaires, and researchers will monitor treatment effects and side effects throughout the study period to better understand how elafibranor works in real-world use.

Researchers are evaluating the change in hemoglobin A1c (HbA1c) levels in people with type 2 diabetes who have not reached their HbA1c goal despite stable treatment with semaglutide or tirzepatide. This phase 2, double-blind study compares the effects of LY3457263, a drug given by subcutaneous injection, with a placebo in this patient group. Participants will be adults aged 18 to 75 with type 2 diabetes and specific HbA1c and BMI criteria. Participants will receive either LY3457263 or a placebo, both administered once weekly by subcutaneous injection. All participants must be on a stable dose of either injectable semaglutide or tirzepatide for at least three months before the study. The treatment period is 24 weeks, during which researchers will monitor changes in HbA1c levels from the start of the study. Throughout the study, participants will undergo assessments to measure HbA1c at the beginning and at week 24. The total participation duration is about 9 months. Researchers will also track participants' safety and treatment adherence during this time to evaluate the effects of LY3457263 compared to placebo in managing type 2 diabetes.

Researchers are evaluating the effectiveness of Saruparib (AZD5305) compared to placebo when added to a standard radiation therapy (RT) and androgen deprivation therapy (ADT) regimen in men with high-risk and very high-risk localized or locally advanced prostate cancer who have a BRCA gene mutation. This phase III study aims to assess whether Saruparib can improve metastasis-free survival in this population. About 700 adult male participants will be randomly assigned to receive either Saruparib or placebo along with ADT. There are two groups: Cohort A includes 400 participants with newly diagnosed high-risk or very high-risk prostate cancer treated with primary RT or with high-risk biochemical recurrence after radical prostatectomy receiving salvage RT. Cohort B includes 300 participants with very high-risk locally advanced prostate cancer receiving primary RT combined with ADT and abiraterone. Saruparib and placebo will be given orally, and standard ADT and abiraterone with prednisone/prednisolone will be administered as per the regimen. Participants will be followed for up to about 93 months to monitor metastasis-free survival and overall safety. Assessments include imaging scans like CT, MRI, bone scans, and PSMA-PET to confirm disease status. The study also monitors organ function, performance status, and treatment adherence. An independent committee will review safety and efficacy data throughout the trial to ensure participant well-being and study integrity.

Researchers are investigating NX-1607, a drug being studied for safety and anti-cancer effects in adults with advanced cancers where standard treatments are ineffective, unavailable, or unsuitable. This first-in-human Phase 1a/1b open-label study focuses on various advanced solid tumors, including ovarian, gastric, head and neck, melanoma, lung, prostate, mesothelioma, breast, urothelial, cervical, colorectal cancers, and certain lymphomas. The study evaluates NX-1607 alone and in combination with paclitaxel, aiming to find safe doses and assess anti-cancer activity. In Phase 1a, patients receive either oral NX-1607 alone or combined with intravenous paclitaxel. The dose escalation phase evaluates safety and tolerability for those with advanced solid tumors lacking effective standard treatments. Phase 1b examines the effectiveness of NX-1607 alone or with paclitaxel at selected doses in specific cancer types. Multiple dose levels may be tested in separate cohorts. Treatments continue according to schedule to monitor response and safety. Participants undergo regular assessments including safety monitoring for adverse events and immune-related side effects over periods up to three years. Researchers measure tumor response using disease-specific criteria. Assessments include physical exams, laboratory tests, biopsies, and imaging to track disease status and treatment effects. Follow-up includes monitoring for serious side effects, treatment discontinuations, and deaths related to therapy, ensuring comprehensive evaluation of safety and anti-cancer activity throughout the study.