Siena

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

This trial evaluates the effectiveness of adjuvant cemiplimab immunotherapy in adults with surgically removed stage II-IIIA non-small cell lung cancer NSCLC who have not previously received adjuvant platinum-based chemotherapy. The study aims to compare disease-free survival between patients treated with cemiplimab and those under observation without additional treatment, focusing on patients with tumors showing PD-L1 expression of 1% or higher. Participants are randomly assigned to receive either cemiplimab or observation. Those in the cemiplimab group receive 350 mg intravenously every 3 weeks for 4 cycles, followed by 700 mg every 6 weeks for up to 6 cycles or until disease relapse or unacceptable side effects occur. The observation group does not receive adjuvant treatment. Treatment continues until relapse, toxicity, or completion of planned cycles. During the trial, participants undergo regular assessments including imaging and laboratory tests to monitor disease status and side effects. The main outcome measured is disease-free survival, tracked for approximately 59 months from randomization. Secondary outcomes include overall survival and the nature and severity of adverse events. Participants are monitored for safety and treatment response throughout the study period, which is expected to conclude in March 2029.

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

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.

Researchers are studying people with idiopathic pulmonary fibrosis IPF or progressive pulmonary fibrosis PPF who have previously taken nerandomilast in another study. The aim is to assess how well patients tolerate long-term treatment with nerandomilast and to evaluate whether it improves lung function and delays worsening symptoms, hospital visits, or death. This open-label extension trial is sponsored by Boehringer Ingelheim and focuses on treatment over an extended period. Participants take nerandomilast tablets for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study involves a single treatment group receiving the drug, and no placebo or comparison groups. Regular visits with doctors help monitor health and collect data during this extended treatment phase. Throughout the study, participants undergo regular lung function tests and health assessments to track any adverse events and changes in lung capacity. The main outcome measured is the occurrence of any adverse events for up to about 99 weeks. Secondary outcomes include changes in forced vital capacity and time to worsening of disease symptoms or hospitalization. The study includes ongoing safety monitoring with a total participation time of up to nearly two years.

Researchers are evaluating the safety and effects of a medicine called fosmanogepix for treating candidemia and invasive candidiasis, which are serious fungal infections caused by Candida yeast. This Phase 3 clinical trial compares fosmanogepix to the standard treatment using caspofungin followed by fluconazole, aiming to show that fosmanogepix is not worse than the standard treatment by a margin of 15%. The study includes adult patients diagnosed with these infections and is sponsored by Basilea Pharmaceutica. Participants are randomly assigned to one of two groups two-thirds receive fosmanogepix intravenously, with an option to switch to oral tablets, while one-third receive caspofungin intravenously followed by oral fluconazole. Matching placebos are given to maintain blinding. Treatments are given daily, first by IV infusion at the clinic and then orally either at the clinic or at home if discharged. Treatment duration can be up to six weeks, depending on infection clearance and symptom improvement. Participants will be monitored through multiple study visits, with assessments including survival status at 30 days, treatment success at the end of treatment, and follow-up evaluations six weeks after stopping treatment. Additional evaluations include clinical and mycological responses, blood cultures, safety monitoring such as adverse events, lab tests, neurological exams, ECGs, and drug concentration measurements. The total study duration for each participant may be approximately 12.5 weeks, considering treatment and follow-up periods.

Researchers are evaluating AZD8965 in a Phase IIb trial to study its safety, tolerability, and effectiveness in treating Idiopathic Pulmonary Fibrosis IPF. The study compares three doses of AZD8965 to a placebo in participants with IPF, including those who are on stable doses of approved antifibrotic therapies such as nintedanib, pirfenidone, or nerandomilast, as well as those not taking antifibrotic treatment. The trial is randomized, placebo-controlled, double-blind, and parallel-group in design. Participants are assigned to one of four groups placebo, low dose AZD8965, medium dose AZD8965, or high dose AZD8965. The treatment lasts for 24 weeks, during which participants receive their assigned medication. The study includes approximately 360 participants across around 200 sites worldwide. Researchers aim to assess the clinical efficacy of AZD8965 by measuring changes in lung function and study the relationship between dose and outcomes. During the study, participants will undergo various assessments including lung function tests such as forced vital capacity FVC, monitoring for adverse events, and pharmacokinetic analyses of AZD8965. Safety and tolerability are monitored up to 25 weeks. Researchers will also track any serious adverse events and treatment discontinuations. The total participation time covers the 24-week treatment period with scheduled visits to assess the study outcomes and participant health.

Researchers are investigating the safety and effectiveness of the Renzan14 Peripheral Stent System in treating patients with femoro-popliteal disease, a type of peripheral arterial disease affecting the leg arteries. This prospective, multicenter, single-arm study plans to include about 100 patients eligible for treatment with this stent. The study focuses on evaluating a modern nitinol stent designed for complex lesions where drug-coated balloons and drug-eluting stents may be less effective or raise concerns about toxicity. The Renzan stent is a self-expanding nitinol device pre-mounted on a catheter designed for precise placement in the affected arteries. It consists of two layers of braided nitinol wire mesh with radiopaque markers to assist in positioning during the procedure. The stent can be partly recaptured during placement if needed. This study observes patients undergoing endovascular implantation of the Renzan stent without comparison groups, focusing on the devices performance and safety after treatment. Participants will be followed for assessments of safety and effectiveness, including measurements at 30 days and up to 12 months after the procedure. Key evaluations include device and procedural success during implantation, rates of death, need for further treatment of the treated artery, artery openness, limb ischemia improvement, major adverse events, and limb amputation at multiple time points up to 36 months. Patients will be monitored closely with follow-up visits to track these outcomes and the long-term performance of the stent.

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.

Researchers are conducting an observational, multicenter, prospective study involving adults with severe eosinophilic asthma who are treated with benralizumab. The study aims to evaluate how often patients achieve partial or complete clinical remission, as defined by SANI criteria. Additionally, it seeks to gather more evidence on benralizumabs immunological effects and its role in asthma treatment, while also consolidating long-term safety data. Participants will be treated with benralizumab 30mg administered subcutaneously according to the approved label and local reimbursement rules. The study will observe patients who have started or plan to start benralizumab within 7 days of enrollment. This real-life study does not involve experimental dosing but follows patients receiving benralizumab in routine clinical practice to collect important data over time. During the study, participants will undergo regular assessments for up to 24 months. Researchers will measure clinical remission rates at multiple time points and monitor asthma control using questionnaires like the Asthma Control Test ACT and Asthma Control Questionnaire ACQ. Lung function tests such as FEV1 and FVC will be evaluated before and after bronchodilator use. Medication use and exacerbation rates will also be tracked. The study focuses on understanding benralizumabs effects and safety in a real-world setting over a long period.