Palermo

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are evaluating treatments for germinal center B-cell-like diffuse large B-cell lymphoma GCB DLBCL, a fast-growing blood cancer affecting immature B-cells. The study compares two treatment combinations to see if more people respond to zilovertamab vedotin MK-2140 plus R-CHP versus polatuzumab vedotin plus R-CHP. This Phase 2 trial aims to assess the effectiveness and safety of these regimens in participants with newly diagnosed GCB DLBCL. Participants receive either zilovertamab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone R-CHP, or polatuzumab vedotin combined with R-CHP. Treatments are given by intravenous infusion on Day 1 of each 3-week cycle for up to 6 cycles, approximately 4 months, with prednisone or prednisolone taken orally for 5 days of each cycle. For participants with high-risk DLBCL, up to 2 additional cycles of rituximab or biosimilar are given. During the study, participants are monitored for response to treatment using Lugano Response Criteria, with follow-up lasting up to about 31 months for the primary outcome. Secondary outcomes include progression-free survival, overall survival, event-free survival, duration of complete response, adverse events, and quality of life assessments. Safety and health status are regularly checked through exams, lab tests, and questionnaires over several years, with total study participation extending up to 7 years.

Researchers are evaluating the efficacy, safety, and tolerability of subcutaneous ianalumab in adults with diffuse cutaneous systemic sclerosis, a condition characterized by skin thickening and other systemic symptoms. This Phase 2 study compares ianalumab to a placebo to understand its impact on this disease, aiming to provide new treatment options for affected individuals. The study is sponsored by Novartis Pharmaceuticals and employs a randomized, double-blind design to ensure reliable results. Participants receive either ianalumab or placebo through subcutaneous injections during the initial 52-week treatment period. After this, all participants enter a second 52-week open-label phase where they receive ianalumab. Following treatment, there is a post-treatment follow-up lasting at least 20 weeks and up to 2 years to monitor long-term effects. The study includes a screening period lasting up to 6 weeks before treatment begins. Throughout the study, participants undergo regular assessments including measuring response based on the rCRISS25 scale at Week 52, lung function tests, skin scoring, and disability index evaluations. Blood samples are taken periodically to measure drug levels and antibodies. Safety is closely monitored through adverse event reporting up to Week 208. The total participation time can extend over several years including treatment and follow-up phases.

Researchers are evaluating the efficacy and safety of enicepatide, a dual GLP-1GIP receptor agonist, at multiple doses compared with placebo for weight management in adults with obesity or overweight and type 2 diabetes mellitus T2DM. This Phase III study aims to better understand how enicepatide affects body weight and other health measures in this population. Participants will be randomly assigned to receive either placebo or one of three dosing regimens of enicepatide, administered once weekly using an integrated drug-device combination product. The study lasts for 72 weeks, during which participants will self-administer the study drug or receive injections from a trained individual if needed. Throughout the study, participants will undergo various assessments including body weight, hemoglobin A1c, waist circumference, fasting glucose and insulin, cholesterol levels, blood pressure, and quality of life questionnaires. Safety will be monitored through adverse event reporting and specific rating scales. This comprehensive evaluation will help determine the effects of enicepatide on weight and diabetes management over the study period.

Researchers are evaluating the effects of enicepatide, a dual GLP-1GIP receptor agonist, at multiple doses compared with placebo for weight management in adults with obesity or overweight who do not have Type 2 diabetes. This Phase III, randomized, double-blind study aims to assess both the efficacy and safety of once-weekly enicepatide in this population, addressing weight-related comorbidities such as prediabetes, hypertension, and cardiovascular conditions. Participants will be randomly assigned to receive either placebo or one of three enicepatide dosing regimens, administered once weekly via an integrated drug-device combination product. The treatment phase lasts through 72 weeks, during which changes in body weight and other health measures are monitored. The study includes multiple assessments to track body weight percentage change, waist circumference, fasting glucose and insulin levels, lipid profiles, blood pressure, and quality of life measures. Throughout the study, participants will undergo regular evaluations including physical examinations, laboratory tests, and questionnaires related to physical functioning and urinary incontinence. Researchers will monitor adverse events, patient-reported health questionnaires, and biomarkers at baseline and weekly intervals through week 72. This long-term follow-up allows for a comprehensive assessment of treatment effects and safety in participants managing obesity or overweight without Type 2 diabetes.

This research aims to assess the effectiveness of a combination of rituximab and golcadomide as a chemotherapy-free treatment for older, frail patients newly diagnosed with Diffuse Large B Cell Non-Hodgkin Lymphoma DLBCL. The study focuses on patients considered frail based on a simplified geriatric assessment sGA and who are not suitable candidates for standard anthracycline-based chemotherapy treatments like R-CHOP. It is a prospective, multicenter, phase II trial designed to explore this targeted approach in a vulnerable population. Participants will undergo an induction phase receiving rituximab, golcadomide, and dexamethasone during the first cycle, with a total of up to six 28-day cycles. Response evaluations occur after the fourth and sixth cycles to determine treatment continuation or discontinuation. Patients achieving at least a partial response proceed to a consolidation phase involving golcadomide alone for up to six additional cycles, possibly alongside involved site radiotherapy on PET-positive areas. Those with stable or progressive disease at interim assessments will stop the protocol treatment and receive alternative therapies. Throughout the study, participants are closely monitored with imaging scans such as PETCT or CT for disease and sarcopenia assessment, and quality of life evaluations at multiple points including baseline, six months, and twelve months. Follow-up continues for 24 months with regular visits to track progression-free survival and overall health. Treatment failures are followed for survival until study completion. The study also records treatment discontinuation rates and quality of life changes to comprehensively understand the treatment impact.

This research aims to evaluate elafibranor, a study drug, compared to a placebo in adults with Primary Biliary Cholangitis PBC and cirrhosis, a liver disease causing bile duct damage and scarring. The trial focuses on whether elafibranor can better prevent worsening of the disease, including progression leading to liver transplant or death, and also assesses long-term safety and symptom impact such as itching and tiredness. Participants will be randomly assigned to take either an 80 mg tablet of elafibranor or a matching placebo tablet once daily, orally, with or without food. This double-blind treatment period can last up to 3.5 years for each participant, with tablets taken at approximately the same time each morning. The study is designed to compare these two groups over the long term. During the study, participants will undergo regular assessments including physical exams, vital signs, electrocardiograms, laboratory tests, and symptom questionnaires at intervals up to 3.5 years. Researchers will measure liver function tests, symptom scales, liver stiffness, and clinical outcomes related to disease progression. Safety is monitored through adverse event tracking and laboratory parameters, with follow-up extending to four weeks after the last dose. Overall participation may last up to 3.5 years.

Researchers are conducting a 10-year global, multi-center observational study to better understand the safety profile of pegvaliase, a treatment for Phenylketonuria PKU. The study focuses on monitoring hypersensitivity reactions, long-term safety, tolerability, and the effectiveness of risk minimization measures used in the European Union. Both new users starting pegvaliase within 30 days of enrollment and those who have already been receiving pegvaliase can participate. Participants in this study will not receive any experimental treatments or undergo special procedures as part of the trial. Instead, their usual pegvaliase treatment and clinical care will continue as normal. Information about their medical history, pegvaliase use, other medications, and safety concerns such as allergic reactions and injection site issues will be collected by their primary physicians. Safety events will be reviewed periodically by an independent committee. Participants are followed according to routine clinical practice, with clinical outcomes assessed regularly, typically monthly during initial treatment phases and every six months during maintenance. The study measures risks of specific safety events over up to 10 years of pegvaliase treatment in a real-world setting. There are no mandatory study visits, and all data collection is based on regular medical care visits.

Researchers are evaluating whether retatrutide and tirzepatide can prevent major adverse liver outcomes in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized controlled trial aims to assess these treatments compared to placebo in about 4,500 adults over approximately 224 weeks. The study is sponsored by Eli Lilly and Company and focuses on liver disease progression and related health measures. Participants will be randomly assigned to receive retatrutide, tirzepatide, or placebo, all administered by subcutaneous injection. The trial includes two placebo groups corresponding to each experimental drug. After completing the main study, eligible participants may join a 2-year extension where all will receive either retatrutide or tirzepatide regardless of their initial assignment. During the study, participants may attend around 25 to 30 clinic visits for health monitoring, study procedures, and assessments of liver function and disease status. Researchers will measure the time to major adverse liver outcomes, changes in liver fibrosis scores, liver stiffness, liver fat content, liver enzyme levels, body weight, and cardiovascular events. Monitoring will continue from baseline through study completion, with detailed evaluations at multiple timepoints including week 104.

Researchers are conducting a large prospective, observational cohort study to evaluate the clinical impact of new Monoclonal Antibodies MAB in patients with B-cell Non-Hodgkin Lymphoma NHL treated in Italian clinical practice. The study focuses on collecting information about the use, feasibility, effectiveness, and both short- and long-term side effects of novel MABs that have been approved by the European Medicines Agency since 2020 and prescribed according to authorized indications in Italy. Participants will be divided into groups based on treatment indication, antibody type, and lymphoma subtype to allow detailed analysis. The study observes patients with B-cell NHL who have received at least one dose of a novel MAB either alone or in combination, as authorized for use in Italy. Both patients receiving first-line treatment and those with relapsed or refractory disease are included. Various cohorts and sub-cohorts will be analyzed to understand outcomes by indication, antibody type, and histological subtype, providing a comprehensive overview of these treatments in real-life settings. Participants will be followed for at least five years to assess outcomes such as overall response rate, complete response rate, progression-free survival, overall survival, event-free survival, time to next treatment, non-relapse mortality, duration of response, and the incidence of early and late adverse events. Clinical data collection will include treatment details, safety monitoring, and long-term follow-up to evaluate both effectiveness and toxicity. The study spans several years, allowing researchers to capture extensive real-world evidence on novel MAB use in B-cell NHL.