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Researchers are evaluating the safety and effectiveness of the drug LY4065967 for treating diabetic peripheral neuropathic pain (DPNP). This study is part of a larger chronic pain master protocol aimed at speeding up the development of new treatments for chronic pain. Participants have diabetic peripheral neuropathy mainly affecting their lower limbs and have had this condition for at least six months. The study compares oral LY4065967 to a placebo, with participants randomly assigned to either group. The trial is a Phase 2, randomized, placebo-controlled clinical trial. Treatments are given by mouth, and participants continue their usual diabetes care with stable treatment for at least 90 days before screening. During the study, researchers monitor changes in average pain intensity using a numeric rating scale from baseline to week 8. Participants undergo assessments including blood sugar control (HbA1c), body mass index measurement, and safety monitoring for heart and vitamin B12 status. The trial is designed for adults aged 18 years and older and includes close observation to ensure participant safety throughout the study period.

Researchers are conducting a prospective, longitudinal, non-interventional, multicenter study to profile molecular biomarkers in patients with head and neck squamous cell carcinoma (HNSCC). The study focuses on individuals with metastatic or unresectable, recurrent HNSCC who are receiving standard of care treatment. The aim is to explore DNA, RNA, immune, and other multiomic biomarkers to better understand prognostic or predictive indicators that could inform future research on relevant biomarkers. Participants will provide tissue and blood samples for molecular biomarker profiling throughout their standard treatment, which involves first line anti-PD1 or PDL1 monotherapy or combination therapy. Tumor tissue samples representative of the current disease must be submitted according to laboratory guidelines. This observational study does not involve any investigational treatments or interventions beyond the participants' usual care. During the study, participants will undergo molecular analyses of their tissue and blood samples over a period of up to 5 years. Researchers will monitor multiomic biomarkers to identify prognostic or predictive factors. The study includes follow-up to collect data that may support the discovery of new biomarkers. Participants must be willing and able to comply with study procedures, including additional blood sample collections.

Researchers are evaluating multiple independent pain treatments under a master protocol designed for chronic pain conditions including osteoarthritis of the knee, chronic low back pain, and diabetic peripheral neuropathic pain. This phase 2 study aims to compare different interventions through disease-state addenda and intervention-specific appendices to better understand their effects on chronic pain. Participants may receive various investigational drugs administered either orally or intravenously, including LY3016859 (IV), LY3556050 (oral), LY3526318 (oral), LY3857210 (oral), or placebo versions given orally or intravenously. Each intervention-specific appendix may begin independently as treatments become available for clinical testing, following the master protocol structure. During the study, participants will be monitored for pain levels using specific scales and assessments related to their condition. Researchers will track the number of participants assigned to each intervention from baseline through week 8. Participants must maintain consistent non-drug pain therapies and discontinue chronic pain medications except for rescue medication during the study. Safety assessments, including physical exams and laboratory tests, will be conducted to ensure participant well-being throughout the trial.

Researchers are evaluating the effectiveness of pemigatinib in adults with advanced or metastatic pancreatic cancer that has spread to nearby tissues, lymph nodes, or distant body parts, and that have specific genetic changes in the FGFR gene. The study focuses on patients whose cancer has FGFR2 gene fusions or other FGFR alterations, aiming to see if pemigatinib can block these abnormal gene functions to stop tumor growth and possibly improve quality of life. This is a phase II trial conducted nationwide using a fully decentralized telemedicine approach to reach participants. Participants receive pemigatinib as an oral medication once daily for 14 days within each 21-day cycle. Treatment continues unless the disease progresses or unacceptable side effects occur. Alongside the drug treatment, patients undergo various imaging tests including CT scans, MRI, optical coherence tomography (OCT), and when needed, whole body bone scans and dilated eye exams (ophthalmoscopy). After finishing treatment, patients are followed up at 30 days and then every four months for one year to monitor their condition. Throughout the study, patients provide blood samples and undergo scans to evaluate treatment response and detect resistance mutations. Researchers track the overall response rate for up to 24 months and assess safety and tolerability. Patients must comply with scheduled visits, tests, and oral medication intake. The total study participation includes treatment cycles and a follow-up period lasting up to approximately 16 months after treatment completion.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating a new approach to prevent cardiovascular events in patients at increased risk due to age and conditions like type 2 diabetes, prediabetes, or metabolic syndrome but without known symptomatic cardiovascular disease. The study compares a Cleerly Coronary Artery Disease (CAD) Staging System-based care strategy with standard risk factor-based care to see if the former can better reduce cardiovascular events. The Cleerly system uses imaging to visualize and quantify coronary artery disease and guides personalized treatment and education based on this assessment. The trial uses the Cleerly CAD Staging System device, which employs a proprietary algorithm to detect and stage coronary artery disease and generate a risk score to guide treatment decisions. Participants receive either this stage-based care or the usual care based on traditional risk factors. The study is prospective, randomized, and pragmatic, designed to follow patients over an average of 3.5 years to compare cardiovascular event outcomes between these two care approaches. Participants will be monitored through cardiovascular event tracking throughout the study period. Data collected includes imaging results, risk scores, and treatment adherence to evaluate the impact of the care strategies. The primary outcome is the comparison of cardiovascular event risk between the Cleerly stage-based care and risk factor-based care groups. The study also includes ongoing safety monitoring and personalized management by a cardiologist-led team via digital communication devices.

Researchers are evaluating how well two new study drugs, CagriSema and cagrilintide, help children and adolescents with excess body weight lose weight. This trial includes participants aged 8 to less than 18 years who have overweight or obesity. The study is designed in two parts: a main study and an extension study. The main study compares CagriSema, cagrilintide, semaglutide (an already approved drug), and placebo, with treatments assigned randomly. Participants receiving semaglutide will not continue to the extension study. The total time in the main study is about 1 year and 6 months, while those in the extension study may participate for up to about 4 years and 10 months. Participants in the main study will receive one of the four treatments by subcutaneous injection. In the extension study, participants will receive either CagriSema or cagrilintide. The study drugs are monitored closely for safety, and participants may experience side effects. The study compares these new treatments to a placebo and an existing approved drug to better understand their effects on weight management in young people. During the study, researchers will measure changes in body mass index (BMI) from baseline to week 68 as the primary outcome. Participants will undergo various assessments including laboratory tests and physical evaluations. The study tracks adherence to treatment and monitors safety throughout the study period. This comprehensive approach aims to provide detailed information about the efficacy and safety of these medications for managing weight in children and adolescents.

Researchers are evaluating corneal endothelial cells in people aged 50 and older who have neovascular age-related macular degeneration (nAMD). The study focuses on participants treated with the Port Delivery System (PDS) refilled every 24 weeks. This Phase IV, open-label trial aims to understand changes in corneal endothelial cell density over time in the eye receiving treatment compared to the fellow eye. The study involves delivering ranibizumab 100 mg/mL via the PDS implant. Supplemental treatment with intravitreal injections of ranibizumab (0.5 mg of a 10 mg/mL formulation) in the study eye may be given if needed. If participants stop the study treatment, they may receive intravitreal ranibizumab injections based on the investigator's judgment. Treatment and monitoring occur over at least 48 weeks. Participants will undergo detailed eye examinations including specular microscopy to measure corneal endothelial cell density at baseline and week 48. Historical visual acuity and imaging data will be reviewed. Researchers will monitor safety, disease activity, and treatment response through visual acuity assessments, optical coherence tomography, and other imaging techniques. The main outcome is the percent change in corneal endothelial cell density in the treated eye compared to the fellow eye after 48 weeks.

Researchers are evaluating the effectiveness of pembrolizumab combined with sacituzumab govitecan-hziy compared to the standard chemotherapy treatments in patients with locally advanced or metastatic urothelial cancer. This Phase III trial focuses on cancers that have spread to nearby tissues, lymph nodes, or other parts of the body. The study aims to compare overall survival and other outcomes such as progression-free survival, response rates, clinical benefits, duration of response, and treatment toxicity between the two treatment approaches. Quality of life and fatigue are also assessed as secondary measures. Participants are randomly assigned to one of two treatment groups. One group receives standard of care chemotherapy, which may include carboplatin or cisplatin combined with gemcitabine, or alternatively docetaxel or paclitaxel, administered intravenously in cycles every 21 days for up to six cycles, unless the disease progresses or side effects become unacceptable. The other group receives sacituzumab govitecan-hziy intravenously on days 1 and 8, along with pembrolizumab intravenously on day 1 of each 21-day cycle, continuing for up to 35 cycles or two years, unless there is disease progression or unacceptable toxicity. Throughout the study, participants undergo regular blood sample collections and imaging scans using computed tomography or magnetic resonance imaging to monitor their condition. Quality of life questionnaires are also completed to assess symptoms and fatigue over time. After treatment ends, patients are followed up 30 days later and then annually for up to five years to evaluate long-term outcomes and safety. The main outcome measured is overall survival from the time of randomization up to five years.

Researchers are investigating the best way to combine chemotherapy and radiation therapy based on how patients with localized non-germinomatous germ cell tumors (NGGCT) in the brain respond to initial chemotherapy. This phase II study aims to optimize radiation treatment for those who respond well to induction chemotherapy to reduce spinal cord relapses, and to use higher dose chemotherapy followed by conventional radiation for patients who do not respond as well. The study evaluates various chemotherapy drugs that work to stop tumor growth in different ways and uses radiation therapy with high-energy x-rays or protons to kill tumor cells and shrink tumors. Participants receive induction chemotherapy with drugs including carboplatin, etoposide, ifosfamide, and thiotepa over multiple cycles. Based on their response, patients are assigned to one of two treatment plans: those with a good response receive whole ventricular plus spinal canal irradiation (WVSCI) radiation therapy, while those with less favorable responses may receive high-dose chemotherapy with peripheral blood stem cell transplantation followed by radiation therapy. Some patients may also undergo second-look surgery depending on their tumor response. Treatments are carefully scheduled and monitored for up to six weeks for radiation and multiple cycles for chemotherapy. During the study, participants undergo regular assessments including MRI scans, cerebrospinal fluid and blood sample collections, and neurocognitive and quality of life evaluations. Researchers monitor tumor response, progression-free survival, overall survival, and treatment side effects for up to 10 years after treatment. Additional evaluations compare outcomes based on radiation type and assess growth and blood counts in younger patients. Patient safety and treatment effectiveness are closely followed throughout the study period.