Bonheiden

Researchers are evaluating the use of epigenome-guided treatment selection compared to the usual standard-of-care (SOC) treatment in adults with active Crohn's Disease (CD) who are starting biologic therapy. This multicenter, prospective, randomized, controlled, open-label study aims to assess the efficacy, safety, and cost-effectiveness of this approach by comparing clinical remission and endoscopic response at Week 26. About 378 participants with active CD, defined by specific clinical and endoscopic criteria, will be included, with roughly half being biologic-naive and the other half exposed to no more than one prior biologic treatment. Participants will be randomly assigned to either receive biologic therapy guided by an epigenetic biomarker assay and the EpiPredict software, which predicts response to two biologics (Vedolizumab or Ustekinumab) or to receive treatment selected according to usual SOC without epigenome guidance. Biologic therapies will be administered following product labels and local SOC recommendations, with dose adjustments allowed as needed. Study assessments will follow the SOC schedule for each biologic during the 26-week treatment period, with different visit weeks depending on the biologic used. Participants will undergo blood sample collection for epigenetic testing during screening. Study visits will include clinical and endoscopic assessments at specified weeks, with long-term follow-up every six months up to 24 months after Week 26 using medical records and questionnaires. Researchers will measure outcomes related to clinical remission and endoscopic response, safety, and cost-effectiveness. Participants' adherence and ability to comply with protocol requirements will be monitored throughout the study.

This research aims to evaluate the safety and effectiveness of BMS-986504, a selective PRMT5 inhibitor, when combined with Nab-paclitaxel and Gemcitabine, compared to a placebo combined with Nab-paclitaxel and Gemcitabine. The study focuses on participants with untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC) who have a specific genetic alteration called homozygous MTAP deletion. This is a randomized Phase 2/3 trial designed to explore treatment options for this patient population. Participants will be assigned to receive either BMS-986504 at specified doses on certain days along with Nab-paclitaxel and Gemcitabine, or a placebo with the same chemotherapy drugs. The treatments are given according to protocol schedules. Some participants may have received up to one cycle of Nab-paclitaxel and Gemcitabine before starting the study treatment, provided they did not experience disease progression or intolerable side effects. The initial cycle must be completed before randomization. During the study, researchers will monitor participants for progression-free survival and overall survival for up to three years after the last participant is randomized. Assessments include measuring tumor response using established criteria (RECIST v1.1). Participants will undergo evaluations to track safety, treatment effects, and disease status throughout the trial period.

Researchers are evaluating the effectiveness of two treatment combinations, 5-FU with nanoliposomal irinotecan (NALIRI) and 5-FU with nanoliposomal irinotecan plus oxaliplatin (NALIRINOX), for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) that has progressed after initial gemcitabine-based therapies. This phase 2 randomized study focuses on patients who are physically fit with good performance status (ECOG 0-1). The main goal is to measure how long patients live without disease progression after starting these treatments. Participants will be randomly assigned to one of two groups. The control group receives NALIRI with 5-FU and leucovorin, while the investigational group receives NALIRINOX, which adds oxaliplatin to the same combination. Dosing varies between groups: NALIRI is given at 70 mg/m² with 2400 mg/m² of 5-FU and 400 mg/m² of leucovorin, while NALIRINOX includes 50 mg/m² of nanoliposomal irinotecan, 2400 mg/m² of 5-FU, 400 mg/m² of leucovorin, and 60 mg/m² of oxaliplatin. The study assesses safety, side effects, tumor response via imaging and tumor markers, and overall survival alongside progression-free survival. During the study, participants will undergo regular assessments including imaging scans to evaluate tumor size and response, blood tests to monitor safety and tumor markers, and evaluations of side effects using standard criteria. Researchers will track progression-free survival at day 85 from randomization as the primary outcome. The study also monitors overall survival and treatment tolerability. Participants must be monitored for safety throughout, with follow-up visits to assess long-term outcomes and treatment effects.

Researchers are evaluating the safety and effectiveness of the Supera Vascular Mimetic Implant, a special stent designed to treat narrowed or blocked areas in the common femoral artery, compared to traditional surgical removal of artery plaque (endarterectomy). This study focuses on patients with Peripheral Arterial Disease classified as Rutherford category 2, 3, or 4. The goal is to see if the implant is at least as effective as surgery and possibly safer for patients. Participants are randomly assigned to one of two groups: one receiving the Supera stent through a minimally invasive procedure involving balloon dilation and stent placement, and the other undergoing standard surgical endarterectomy. The procedure involves crossing the lesion with a guidewire, angiographic assessment, and optional post-dilation for the stent group. The surgery group receives treatment according to standard care. Follow-up visits are scheduled at 1, 6, 12, 24, and 36 months after the procedure. Throughout the study, patients will undergo assessments including physical exams, walking ability questionnaires, blood tests, ankle and toe blood pressure measurements, and ultrasound imaging to check blood flow. Researchers will monitor for outcomes such as artery openness (patency), need for additional treatments, wound healing, and any adverse events up to 36 months. Primary outcomes focus on artery openness at 12 months and safety within 30 days post-procedure.

Researchers are investigating the safety and effectiveness of eloralintide compared to a placebo in adults with persistent obesity or overweight. This includes people with or without type 2 diabetes who are already on stable weekly incretin therapy. The study is a phase 3, randomized, double-blind trial focusing on this specific group to better understand treatment outcomes. Participants will receive either eloralintide or a placebo, both given by subcutaneous injection once a week. The study compares these two treatments over the course of the trial. Participants must continue their stable incretin therapy throughout the study period. The study lasts about 80 weeks in total. Researchers will monitor changes in body weight from the start of treatment to week 64 as the main outcome. Participants will have regular assessments to track their health, safety, and treatment effects during this time.

Researchers are evaluating a new treatment approach for colon cancer, focusing on patients with previously untreated T4N0 or Stage III mismatch repair proficient/microsatellite stable (MMRp/MSS) colon cancer. This study compares the combination of dostarlimab and CAPEOX chemotherapy (capecitabine plus oxaliplatin) given before surgery, called neoadjuvant therapy, against CAPEOX chemotherapy alone. The goal is to see if the combined treatment shows early signs of better effectiveness and to explore blood and tumor markers that might predict treatment response. The study involves two treatment groups: one receiving dostarlimab plus CAPEOX and the other receiving CAPEOX alone. Dostarlimab is a biological therapy administered alongside the chemotherapy drugs capecitabine and oxaliplatin. These treatments are given before surgery to remove the tumor. The study is open-label and randomized, meaning participants are assigned by chance to one of the two treatment options without masking. Participants undergo assessments up to approximately 18 weeks to measure major pathological response rates, which indicate how well the tumor responds to treatment. Safety is monitored throughout the study and up to about 105 weeks, including tracking adverse events, serious adverse events, immune-mediated adverse events, and any treatment discontinuations or deaths related to side effects. This long-term monitoring helps evaluate both the effectiveness and safety of the treatment approaches.

Researchers are evaluating the effects of the drug orforglipron compared with a placebo on cardiovascular outcomes in adults who have atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). This is a Phase 3, randomized, double-blind, placebo-controlled study designed to investigate major adverse cardiovascular events over a long period. Participants will receive either orforglipron or a placebo orally. The study is event-driven and will continue until the occurrence of major cardiovascular events or up to about 5 years. The treatments are administered without revealing to participants which group they are in to ensure unbiased results. During the study, participants will be monitored for the time to the first occurrence of a major cardiovascular event. Researchers will collect data from baseline through the end of the study, which lasts approximately 5 years. Regular assessments will help evaluate the safety and effects of the treatments on cardiovascular health in this population.

This research aims to evaluate the effectiveness of trastuzumab deruxtecan (T-DXd) in adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously been treated with a trastuzumab-based regimen. The study also collects patient demographic and clinical information, treatment patterns, and safety data including serious adverse events and drug reactions. It includes a disease registry for patients receiving conventional therapies in a real-world European setting. The study is non-interventional, meaning no investigational drugs are administered beyond standard care. Patients receiving T-DXd will be treated according to the Summary of Product Characteristics (SmPC), and data on conventional therapies such as platinum-fluoropyrimidine chemotherapy, nivolumab, ramucirumab-paclitaxel, taxane, irinotecan, and pembrolizumab will also be gathered. Treatment choices and administration follow the physician's decision and routine clinical practice. Participants will be monitored from baseline to about two years to assess the time to next treatment. Researchers will collect clinical data, treatment details, tolerability, and patient surveys to understand outcomes and safety. The study involves regular follow-up and data collection to track treatment effectiveness and patient experience in real-world settings.

Researchers are evaluating the safety and effectiveness of combining vedolizumab with upadacitinib, called dual targeted therapy (DTT), compared to using vedolizumab alone (monotherapy) in adults with moderately to severely active Crohn's Disease. The main goal is to see if DTT better reduces bowel inflammation and ulcers after 12 weeks of treatment. This Phase 3b trial involves about 396 participants worldwide and also aims to assess the long-term safety and efficacy of these treatments. Participants are randomly assigned in equal numbers to receive either vedolizumab plus upadacitinib or vedolizumab plus placebo during a 12-week induction phase. Those who respond well, showing a significant reduction in disease activity, then continue to a 40-week maintenance phase receiving vedolizumab alone. After this, participants undergo an 18-week safety follow-up period, making the total study participation approximately 70 weeks. During the study, participants will visit the clinic 15 times for assessments including evaluations of disease activity, endoscopic examinations, and safety monitoring. The main outcome measures include the percentage of participants achieving clinical remission and showing improvement in bowel inflammation at Week 12. Researchers will track effectiveness, adverse effects, and overall health throughout the treatment and follow-up periods.

Researchers are evaluating zolbetuximab combined with pembrolizumab and chemotherapy in adults with locally advanced, unresectable, or metastatic stomach or gastroesophageal junction (GEJ) cancer. This study focuses on cancer cells that are HER2-negative but positive for the Claudin 18.2 protein and PD-L1, exploring how well zolbetuximab helps the immune system attack the tumor alongside immunotherapy and chemotherapy. The trial is a phase 3, randomized, double-blind study designed to compare the overall survival of participants receiving zolbetuximab with pembrolizumab and chemotherapy versus those receiving a placebo with pembrolizumab and chemotherapy. Participants receive study treatment in 6-week cycles, with zolbetuximab or placebo given by infusion every 2 or 3 weeks. Chemotherapy regimens include either CAPOX (capecitabine tablets and oxaliplatin infusion) or mFOLFOX6 (infusions of 5-fluorouracil, folinic acid, and oxaliplatin) administered on schedules matching the cycles. Pembrolizumab is infused every 3 or 6 weeks. Treatment continues until cancer worsens, is not tolerated, or another therapy is needed, with pembrolizumab given for up to 2 years. After initial cycles, some chemotherapy drugs are adjusted to only include oral capecitabine or certain infusions. During the study, participants visit the clinic for treatments, health checks, and scans to monitor cancer changes and side effects. Researchers also track medical problems related to the treatments and may collect tumor samples if cancer worsens. After stopping treatment, participants have follow-up visits and scans every 9 to 12 weeks, along with telephone check-ins every 3 months. The primary outcome measured is overall survival up to 72 months, with ongoing monitoring to evaluate safety and treatment effects.