Veldhoven

Researchers are evaluating the efficacy and safety of rilvegostomig compared to pembrolizumab, both combined with platinum-based doublet chemotherapy, as a first-line treatment for patients with locally advanced or metastatic non-squamous non-small cell lung cancer NSCLC whose tumors express PD-L1 at levels of 1% or higher. This Phase III, randomized, double-blind, global study aims to compare these treatments to improve outcomes for this patient group. Participants will receive either rilvegostomig or pembrolizumab, each given intravenously on Day 1 of every 21-day cycle, combined with platinum-based doublet chemotherapy either carboplatin or cisplatin also given on Day 1 of each cycle for up to four cycles. After chemotherapy cycles, patients continue with rilvegostomig or pembrolizumab monotherapy combined with pemetrexed maintenance. The study follows patients for up to approximately six years to monitor treatment effects and safety. During the study, participants undergo assessments including imaging scans to measure tumor size, blood tests to evaluate organ function, and questionnaires about symptoms and quality of life. Researchers monitor overall survival and progression-free survival as primary outcomes, alongside other measures such as response duration and physical functioning. Safety is closely observed throughout, with study visits scheduled regularly during treatment and follow-up periods, lasting up to six years in total.

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with platinum-based chemotherapy compared to pembrolizumab combined with platinum-based chemotherapy as a first treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer mNSCLC whose tumors express programmed death-ligand 1 PD-L1. This Phase III global study focuses on patients with PD-L1 tumor cell expression of 1% or higher and aims to determine which treatment provides better overall and progression-free survival. Participants will be randomly assigned to one of two study groups one group will receive rilvegostomig plus carboplatin and either paclitaxel or nab-paclitaxel chemotherapy, while the other group will receive pembrolizumab plus the same chemotherapy options. Rilvegostomig and pembrolizumab are both given intravenously on Day 1 of each 21-day cycle, with chemotherapy given up to 4 cycles. Nab-paclitaxel may be administered on Days 1, 8, and 15 of each cycle. Treatment continues with rilvegostomig or pembrolizumab until disease progression or other criteria are met. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests to monitor organ function, and patient questionnaires about physical function and quality of life. Researchers will track overall survival, progression-free survival, response rates, and duration of response for up to approximately 6 years. Safety and immune response to rilvegostomig will also be evaluated. Participants will be closely monitored throughout the treatment and follow-up periods.

Researchers are evaluating the safety and effects of a new medicine called NNC0487-0111 in people who have Heart Failure with preserved Ejection Fraction HFpEF or Heart Failure with mildly reduced Ejection Fraction HFmrEF and excess body weight. This phase 3 clinical trial aims to find out if NNC0487-0111 is safe and effective for treating these conditions compared to a placebo. Participants have HFpEF or HFmrEF and a body mass index of 30 or above. The study is sponsored by Novo Nordisk AS and uses a randomized, quadruple-masked design. Participants will receive either NNC0487-0111 or a matching placebo by injection under the skin once a week. The NNC0487-0111 is given in increasing doses over time. The study is parallel in design, meaning participants are randomly assigned to one of the two groups and receive that treatment throughout the trial. This treatment period extends for up to about 165 weeks. The study evaluates the time to certain heart failure events, hospitalizations, cardiovascular deaths, and other major cardiovascular events. During the study, participants will be monitored regularly to assess heart failure outcomes and kidney function, as well as quality of life using questionnaires like the Kansas City Cardiomyopathy Questionnaire. Safety and effectiveness are assessed through hospital visits, heart failure event tracking, and blood tests including kidney function and blood sugar levels. The total participation spans over three years, with ongoing evaluations to measure the time to heart failure events and cardiovascular outcomes. Participants receive close medical monitoring throughout the study period.

Researchers are evaluating orforglipron to measure its effects on cardiovascular outcomes in adults aged 50 and older who have atherosclerotic cardiovascular disease ASCVD andor chronic kidney disease CKD. This phase 3 study aims to compare orforglipron with a placebo to better understand its impact on major cardiovascular events over about five years. Participants will be randomly assigned to receive either orforglipron orally along with standard care or a placebo orally along with standard care. The study is double-blinded, meaning neither participants nor researchers will know who receives the active drug or placebo during the trial period. During the study, participants will be followed for around five years, with researchers monitoring the time to the first major cardiovascular event and additional outcomes such as cardiovascular and kidney events, changes in kidney function measured by eGFR, and the onset of type 2 diabetes. The study includes regular assessments to track these outcomes and ensure participant safety throughout the long-term follow-up.

Researchers are evaluating the clinical benefit of combining Navlimetostat BMS-986504, a selective MTA-cooperative inhibitor of PRMT5, with pembrolizumab and chemotherapy compared to placebo plus pembrolizumab and chemotherapy. This study focuses on participants with first-line metastatic non-small cell lung cancer NSCLC who have a homozygous MTAP deletion. The trial is a randomized Phase 23 study aimed at advancing treatment options for this specific lung cancer group. Participants will receive one of several combinations Navlimetostat plus pembrolizumab and chemotherapy, or placebo plus pembrolizumab and chemotherapy. Chemotherapy drugs involved may include cisplatin, carboplatin, pemetrexed, paclitaxel, or nab-paclitaxel, given at specified doses on certain days. The study uses a quadruple-masked, parallel design with multiple treatment arms to compare these regimens. During the study, participants will be monitored for progression-free survival and overall survival up to five years. Researchers will assess tumor response, disease control, duration and time to response, and safety through adverse event reporting and laboratory tests. The study includes detailed follow-up to evaluate efficacy and safety outcomes over the long term, with a primary completion date in 2031.

Researchers are evaluating the effect of PKN605, an oral medication, on atrial fibrillation, a condition affecting heart rhythm. This Phase 2 study is designed as a randomized, double-blind, placebo-controlled trial to assess how well PKN605 reduces the time participants spend in atrial fibrillation, as well as its safety, tolerability, and how the body processes the drug. The study is sponsored by Novartis Pharmaceuticals and aims to provide detailed information about the treatments impact on this heart condition. Participants will first undergo a screening period of up to 90 days to confirm eligibility. Those who qualify will be randomly assigned to receive one of two doses of PKN605 or a matching placebo. The treatment phase lasts 24 weeks, during which participants take the oral study drug and attend clinic visits about once a month. Their heart rhythm will be monitored using ECG devices throughout the study. After completing treatment, participants will have a final safety follow-up visit approximately one month later. During the study, participants will have regular ECG monitoring to measure atrial fibrillation burden and check for recurrence. Additional assessments include pharmacokinetic sampling to measure drug concentration at specific times after dosing. Researchers will evaluate the primary outcome of atrial fibrillation burden over 24 weeks and secondary outcomes related to recurrence and drug levels. Safety and tolerability are closely monitored, and participants usual heart care continues alongside study participation.

Researchers are studying the role of amniotic fluid in the development and microbial colonization of the intestinal tract in extremely preterm infants born between 24 and 27 weeks of gestation. The study aims to understand how changes in amniotic fluid composition relate to conditions like chorioamnionitis and fetal growth restriction, and how these changes might affect neonatal outcomes such as necrotizing enterocolitis and sepsis. This observational study involves detailed profiling of amniotic fluid and early gut microbiota to identify patterns linked to these risks. The study collects about 5 mL of amniotic fluid from mothers delivering extremely preterm infants either vaginally or via cesarean section. It also includes a reference group of pregnancies at various gestational ages, from early midtrimester to full term. The collected fluid is analyzed using advanced biomedical techniques for microbial and metabolic profiles. Neonatal fecal samples will also be studied at days 0, 7, 14, 21, and 28 to examine early gut colonization. Participants will be involved through the collection of amniotic fluid at birth and neonatal stool samples over the first month of life. Researchers will monitor and analyze amniotic fluid characteristics in relation to chorioamnionitis, fetal growth restriction, and neonatal health outcomes including necrotizing enterocolitis and sepsis. The study aims to improve understanding of gastrointestinal development in preterm infants and identify high-risk cases, potentially guiding future interventions. The total study duration spans from birth through the first 28 postnatal days for microbiota monitoring.

This research aims to better understand unexplained bleeding in individuals diagnosed with a bleeding disorder of unknown cause BDUC. It focuses on why these patients have an increased tendency to bleed and how this affects their daily life and overall health. The study addresses important questions about the underlying mechanisms of bleeding, the impact on quality of life, and how care is currently provided and can be improved for these patients. Participants aged 12 years and older with an increased bleeding tendency who remain undiagnosed after standard lab tests will be enrolled across Hemophilia Treatment Centers in the Netherlands. The study is observational and involves blood sampling for advanced hemostasis and genetic testing, as well as completing questionnaires. Participants will be followed over 10 years to assess changes and effects of bleeding symptoms. During the study, participants will undergo blood tests and provide detailed health information through questionnaires. Researchers will monitor bleeding symptoms, severity, physical activity, patient activation, and healthcare satisfaction over time. The main outcomes measured include health-related quality of life and diagnostic findings. The study also evaluates care pathways and aims to develop improved diagnostic and treatment strategies based on collected clinical, laboratory, and patient-reported data.

This trial investigates the effectiveness of vaginal cerclage compared to standard treatment in women with twin pregnancies who have a short cervix or cervical dilatation in midpregnancy. The study focuses on preventing extreme preterm birth before 28 weeks of gestation, a serious concern due to high rates of perinatal death in this group. The research aims to provide evidence on whether cerclage can reduce early births and improve outcomes for babies and families. Participants will be randomly assigned to receive either a vaginal cerclage or standard care without cerclage. The cerclage procedure involves placing an unabsorbable suture around the cervix under anesthesia to strengthen and close it, aiming to prevent cervical insufficiency. The comparison group will follow current Dutch guidelines, which do not include cerclage for this condition. During the study, participants will be monitored for preterm birth rates and various maternal and neonatal health outcomes up to three months after birth. Assessments include gestational age at delivery, days on ventilation and in neonatal intensive care, maternal quality of life, and adverse events. The primary measure is the rate of extreme preterm birth before 28 weeks. The trial will continue until December 2028, with ongoing evaluation of both short-term and longer-term effects.

Researchers are studying patients with non-metastatic stage II colon cancer who are part of the Dutch ColoRectal Cancer cohort PLCRC and who consented to additional blood samples. The study aims to evaluate how many patients with detectable circulating tumor DNA ctDNA after surgery begin adjuvant chemotherapy. This observational and interventional trial includes patients who do not have a standard indication for chemotherapy and involves a randomized design to compare ctDNA-guided treatment with standard care. Patients are randomly assigned to one of two groups the ctDNA-based treatment group or the standard care group. In the ctDNA group, blood samples taken after surgery are analyzed for ctDNA. Those with detectable ctDNA are offered 3 months of adjuvant chemotherapy using CAPOX a combination of fluoropyrimidine and oxaliplatin. Patients without detectable ctDNA receive routine follow-up care. The standard care group receives routine follow-up without knowledge of their ctDNA results. Participants will have blood collected before surgery, after surgery, and during follow-up. Researchers will monitor who starts chemotherapy within 8 to 12 weeks after surgery and will track recurrence rates, disease-free survival, overall survival, time to recurrence, quality of life, and cost-effectiveness over several years. Follow-up assessments occur up to 10 years, allowing detailed long-term evaluation of treatment impact and patient outcomes.