Bari

Researchers are evaluating remibrutinib (LOU064) in adolescents aged 12 to under 18 years who have chronic spontaneous urticaria (CSU) that is not well controlled by H1-antihistamines. This Phase 3 trial aims to assess the effectiveness, how the drug is processed in the body, and safety of remibrutinib compared to a placebo. The study also intends to gather long-term data on how well remibrutinib works and its safety over several years after treatment ends. The trial includes three periods. First, the core period is a 24-week double-blind phase where about two-thirds of participants receive remibrutinib and one-third receive placebo, with about 10 site visits over approximately 32 weeks. Next is an optional open-label extension lasting from one to three years, where participants who completed the core period may receive remibrutinib or enter an observational treatment-free phase depending on their symptoms. Participants may cycle through treatment and observational periods up to six times. Finally, an optional long-term treatment-free follow-up can last up to three years with one site visit and up to four phone calls. During the study, participants undergo assessments including changes in urticaria activity scores (UAS7), itching severity (ISS7), and hive severity (HSS7) measured from baseline to 12 weeks. Regular visits monitor safety, symptoms, and drug effects. The study tracks these measures to understand remibrutinib's impact on CSU symptoms and overall safety profile during and after treatment, with total participation potentially lasting several years.

Researchers are creating a national registry in Italy for multiple myeloma, a type of blood cancer that makes up about 1.3% of all tumor diagnoses in men and 1.2% in women. This registry aims to track current clinical practices and describe how patients with multiple myeloma are diagnosed and treated across various hematology centers in Italy. The study also includes a patient-powered registry to encourage patient involvement and better understand treatment patterns and outcomes. The study is observational, meaning it will not involve any experimental treatments but will collect data on routine care and outcomes for patients diagnosed with active or symptomatic multiple myeloma since January 1, 2019. Both physicians and patients will contribute information to the registry, which will help monitor standard care practices nationwide. Participants will be followed to measure important outcomes such as overall survival and the time until the next treatment over a three-year period. The registry will collect data to analyze treatment approaches, patient characteristics, and survival, helping to identify changes and differences in care across Italy. Patients aged 18 years and older who can provide informed consent are eligible to participate, and there are no exclusion criteria.

Researchers are studying advanced renal cell carcinoma (RCC) that has returned after prior adjuvant therapy. The trial aims to find out if treatment with belzutifan and zanzalintinib helps patients live longer and delays disease progression compared to treatment with cabozantinib. This is a Phase 3 randomized study focusing on participants with recurrent advanced RCC who have previously received anti-PD-1/L1 therapy. Participants are randomly assigned to receive one of two oral drug regimens: either belzutifan combined with zanzalintinib, both taken once daily, or cabozantinib alone, also taken once daily. The study compares these treatments to assess their effects on disease control and overall survival. During the study, participants will be monitored for progression-free survival and overall survival for up to approximately 73 months. Researchers will evaluate how well the cancer responds to treatment and track any changes in health status over time. Safety and effectiveness of the treatments will be closely followed throughout the study period.

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 conducting a global, multicenter, prospective observational registry to study patients with Pompe disease, including those with late-onset Pompe disease (LOPD) and infantile-onset Pompe disease (IOPD). The study includes both patients who are untreated and those receiving approved Pompe disease therapies. The main goals are to assess the long-term safety and real-world effectiveness of these treatments, understand their impact on quality of life and patient-reported outcomes, and describe the natural history of untreated Pompe disease. Participants may be treated with various therapies including enzyme replacement therapies such as cipaglucosidase alfa delivered by intravenous infusion, alglucosidase alfa or avalglucosidase alfa once approved locally, and miglustat co-administered with ATB200. Patients not receiving any medical therapy for Pompe disease are also included. The study gathers data from both treated and untreated patients as they are managed in routine clinical practice. Throughout the study, participant data will be collected to monitor the frequency of adverse events and serious adverse events over a period of five years. Researchers will also evaluate treatment effectiveness, quality of life, and patient-reported outcomes during this time. This observational approach allows for long-term safety monitoring and understanding of Pompe disease progression in a real-world setting.

Researchers are studying the long-term effects of a non-drug program that includes various activities such as physical exercise, choir singing, learning sessions, and horticulture to help prevent cognitive decline in elderly people living independently who show signs of frailty. The study aims to find out if participating in multiple activities including music can slow down the loss of thinking and hearing abilities, promote positive brain changes, and reduce feelings of loneliness by providing social engagement. This research involves community-dwelling older adults and compares those involved in a music-inclusive program to groups doing activities without music or no activities at all. The intervention lasts for 9 months and includes a multidomain program combining physical, cognitive, social, and musical activities through choir participation. One group participates in this multidomain intervention, while another group engages in general physical, manual, or intellectual activities without music, and a control group remains passive. Participants keep diaries to record the time spent on their activities, helping to monitor adherence. Participants are tested three times: before starting, after completing the 9-month program, and again at a 6-month follow-up. Researchers collect saliva samples to measure Brain-Derived Neurotrophic Factor (BDNF), a protein important for brain health and plasticity, as well as conduct audiometric, neuropsychological, and frailty assessments. They also evaluate cognitive functioning, hearing ability, speech understanding in noise, and socio-psychological well-being to see if the intervention benefits brain and overall health in aging individuals.

Researchers are studying older adults with non-communicable chronic diseases (NCDs) to evaluate a personalized prevention program based on the Comprehensive Geriatric Assessment (CGA). This program aims to reduce the risk of frailty and hospitalization by identifying those at high risk and providing tailored preventive care. The study is being conducted in a primary care setting across four Italian regions with 1216 participants enrolled by their general practitioners (GPs). Participants are divided into two groups: one receives the personalized prevention program (PPP) guided by the CGA, and the other follows standard clinical care. The intervention group undergoes evaluations at the start, 6 months, and 12 months using the CGA, Resilience Scale, and Psychological General Wellbeing Index. They also provide saliva samples for biological analysis. The prevention program is given at baseline, with follow-up checks on adherence and satisfaction. Throughout the 12-month study, researchers will monitor hospitalization rates as the primary outcome. Participants in both groups are contacted twice for follow-up assessments. Data collected includes clinical evaluations, questionnaires, and saliva sample analysis to explore links between biological markers and health outcomes. The study will also analyze differences between groups to assess the program's impact on reducing hospitalizations among older adults with NCDs.

Researchers are evaluating the safety, tolerability, and effectiveness of sonrotoclax alone and combined with other drugs in patients with relapsed or refractory multiple myeloma with a specific chromosomal translocation called t(11;14). This Phase 1b/2 study focuses on patients whose disease has returned or not responded to previous treatments, aiming to understand how well sonrotoclax works in these settings. The study assesses sonrotoclax given by mouth daily, either alone or combined with dexamethasone (given once weekly by mouth or intravenously), carfilzomib (weekly intravenous), daratumumab (weekly under the skin), or pomalidomide (daily by mouth). Different combinations are tested to find safe and effective dosing. The study includes dose-escalation and cohort-expansion phases to explore various treatment regimens. Participants will be closely monitored for side effects and treatment responses over time. Researchers will track dose-limiting toxicities during the first 28 days, adverse events up to 30 days after the last dose, and long-term responses over approximately 4 years. Assessments include measuring disease markers and overall response rates. Safety and efficacy data will guide future treatments for this patient population.

Researchers are investigating how plant-based diets might change the gut microbiome and increase the production of beneficial short-chain fatty acids (SCFAs) in patients with smoldering multiple myeloma (sMM). The goal is to see if these dietary changes can support a healthier immune balance and potentially prevent progression to active multiple myeloma. This national, prospective, multicenter study will include up to 62 sMM patients and focuses on understanding how diet impacts gut bacteria and immune cell ratios in this population. Participants who qualify and enroll will be encouraged to follow a balanced, high-fiber diet for 12 weeks, choosing from various diet plans or individual foods based on their preferences. Nutritional counseling will be provided at enrollment, one month later, and as needed. Medical visits will be free and conducted at enrollment and week 12. Patients will be asked to track their daily diet choices through questionnaires throughout the study. Stool and blood samples will be collected at baseline, 4 weeks, and 12 weeks to assess changes in gut microbiota and immune markers. Study participants will undergo routine clinical follow-up that includes bone marrow and blood sample collection at screening, as well as stool sampling at the start, 4 weeks, and 12 weeks after beginning the diet. Researchers will measure the mean SCFA concentration in stool samples to evaluate the diet's effects. Dietary adherence will be monitored via questionnaires. The overall study duration for each participant is 12 weeks, during which their health and immune response will be closely observed to understand the impact of the plant-based diet.

Researchers are conducting a large prospective, observational cohort study to assess the clinical impact of new monoclonal antibodies (MAB) in treating B-cell Non-Hodgkin Lymphoma (NHL) within Italian clinical practice. The study focuses on patients needing treatment for B-cell NHL, including those receiving first-line or relapsed/refractory therapy. The novel MAB being studied have received approval from the European Medicines Agency (EMA) since 2020 and are prescribed according to authorized marketing indications in Italy. Participants will receive novel MAB treatments either alone or in combination, prescribed based on EMA-approved indications since 2020. Patients will be grouped into cohorts according to the treatment indication, antibody type, and lymphoma subtype, with additional sub-cohorts created if necessary. This design allows analysis by indication, antibody type, subtype, and overall evaluation of the entire patient cohort. Throughout the study, researchers will collect clinical information to evaluate the use, feasibility, efficacy, and toxicity of these novel antibodies. Key outcomes measured over at least five years include 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 incidence of early and late adverse events. Participants will be closely monitored for both short- and long-term effects of the treatments.