The Hill

Researchers are conducting a Phase 1 trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug INI-822 in healthy volunteers and participants with Metabolic Dysfunction-Associated Steatohepatitis MASH or presumed MASH. The study includes multiple parts involving different groups, including healthy adults and those diagnosed with MASH, to understand the drugs effects and behavior in the body. The trial consists of six parts, enrolling approximately 168 participants divided into cohorts. Participants will receive oral doses of INI-822 or matching placebo once daily. The study includes single ascending dose SAD and multiple ascending dose MAD phases, crossover assessments for food effects, and pharmacodynamic evaluations in participants with MASH or presumed MASH. Study durations for participants vary from 5 to 18 weeks depending on the part. Participants will attend screening visits and receive study drug or placebo as assigned. Researchers will monitor safety through adverse event tracking and laboratory tests, assess drug levels in the blood, and evaluate pharmacodynamic responses. The study is randomized and double-blinded, with close monitoring throughout each part. Total participation time depends on the cohort but may last up to 18 weeks including screening.

Researchers are evaluating the addition of Tersolisib LY4064809STX-478 to other anti-cancer drugs as a first treatment for adults with advanced hormone receptor-positive HRhuman epidermal growth factor receptor 2-negative HER2- breast cancer that has a PIK3CA mutation. This Phase 3 randomized, double-blind, placebo-controlled trial aims to understand the efficacy and safety of this combination compared to placebo, focusing on improving outcomes for patients with this specific genetic change. Participants receive LY4064809 orally in one of two doses combined with a CDK46 inhibitor such as Ribociclib, Palbociclib, or Abemaciclib and endocrine therapy ET administered orally or via intramuscular injection. The comparison group receives a placebo combined with the same CDK46 inhibitor and ET. The study includes two parts Part 1 explores dose optimization, and Part 2 evaluates the treatment combinations effectiveness and safety as a first-line therapy. During the study, participants will have regular assessments to monitor cancer response, progression, and safety over an estimated period of up to 5 years or more. Researchers will measure outcomes such as overall response rate, progression-free survival, duration of response, overall survival, and quality of life. Treatment continues as long as the cancer benefits without intolerable side effects. Safety monitoring, laboratory tests, and quality of life questionnaires are part of the participant involvement throughout the trial.

This research aims to evaluate how tirzepatide affects body weight and cardiovascular risk factors in adolescents aged 12 to 17 who have obesity along with multiple weight-related health conditions. The study is a Phase 3 clinical trial focusing on the safety and effectiveness of tirzepatide combined with healthy nutrition and physical activity. Participants will be randomly assigned to receive either tirzepatide or a placebo through weekly injections under the skin. The main study period lasts about 72 weeks with up to 23 visits, and participants who completed a prior related study and meet certain criteria may continue receiving tirzepatide for an additional 156 weeks while maintaining lifestyle interventions. During the study, participants will undergo various assessments including measurements of body mass index BMI, blood pressure, blood sugar HbA1c, triglycerides, body fat by DXA scan, and sleep apnea index. Researchers will monitor changes from baseline to week 72 in these areas to evaluate the treatments impact. Safety and adherence to the study schedule will also be closely observed throughout the trial.

Researchers are evaluating the efficacy, safety, and tolerability of BMS-986368 in adults with Multiple Sclerosis Spasticity. This Phase 2 randomized, double-blind, placebo-controlled study aims to assess three different doses of this oral FAAHMAGL inhibitor to better understand its impact on spasticity symptoms in participants diagnosed with MS who have experienced spasticity for at least six months. Participants will be randomly assigned to one of four groups receiving either one of three doses of BMS-986368 or a placebo. The medication is administered orally on specified days during the study period. The trial includes a treatment phase lasting six weeks, followed by safety monitoring up to 16 weeks to evaluate adverse events and treatment tolerability. During the study, participants will undergo assessments including the Total Numeric-transformed Modified Ashworth Scale for the most affected lower limb, Numeric Rating Scale for Spasticity, MS Spasticity Scale, Timed 25-Foot Walk, and Clinical Global Impression of Severity. Researchers will monitor plasma drug levels and adverse events, including suicidal ideation and withdrawal symptoms, throughout the trial. The study duration and follow-up span up to 16 weeks from treatment start.

Researchers are evaluating a combination treatment including stereotactic body radiotherapy and durvalumab added to a well-tolerated two-week chemotherapy and radiation regimen for adults with esophageal cancer that is locally advanced or has spread to other parts of the body. This Phase II trial aims to see if this combined approach can help the bodys immune system control cancer progression and improve swallowing difficulties. All participants will receive ten daily radiotherapy sessions to the primary esophageal tumor over two weeks alongside weekly intravenous chemotherapy with carboplatin and paclitaxel. Durvalumab, an immune therapy given intravenously, starts at the beginning of radiation and continues every four weeks for up to 24 months or until the cancer worsens. Participants with metastatic tumors will also receive three doses of stereotactic radiotherapy to metastases one month after initial treatment. Throughout the study, participants will undergo regular safety blood tests every two to four weeks and CT scans every six weeks up to week 24, then every 12 weeks until disease progression. They will also complete questionnaires about wellbeing and nutrition. Researchers will track progression-free survival, symptom relief, nutritional status, quality of life, response rates, toxicity, and survival over the study period, which may last up to two years.

Researchers are evaluating whether accelerated BEP chemotherapy is more effective than the standard BEP regimen for males aged 11 to 50 years with intermediate and poor-risk metastatic germ cell tumors. This phase 3 randomized trial aims to improve cure rates for these patients, as current treatments have limited success for higher-risk disease. The study is led by the University of Sydney and focuses on first-line chemotherapy outcomes for metastatic germ cell tumors. The study compares two treatment schedules standard BEP chemotherapy given every 3 weeks for 4 cycles, and accelerated BEP given every 2 weeks for 4 cycles followed by additional bleomycin doses. Both regimens include bleomycin, etoposide, cisplatin, and supportive growth factors like pegylated G-CSF or filgrastim, with dosing adjusted by age and weight. Treatment lasts about 12 weeks in both arms. Participants will undergo treatment cycles with regular intravenous chemotherapy infusions and weekly bleomycin doses. Researchers will assess progression-free survival up to 5 years after randomization, along with tumor response at the end of treatment and at 6 months. Safety will be monitored through adverse events, and quality of life will be measured up to 18 months. Overall survival and chemotherapy dose intensity are also tracked. The study involves multiple assessments and follow-up visits to monitor effects and outcomes.

Long bone defects LBD are focal losses of bone tissue in the long bones of the arms or legs, often caused by trauma, tumors, or infections. Post-traumatic defects make up the largest group and present complex treatment challenges. This international, multicenter registry aims to collect detailed information on the prevalence, treatment methods, complications, and outcomes of post-traumatic long bone defects to improve clinical knowledge and care. Patients with long bone defects will be included from multiple centers over a 3-year period, aiming to enroll at least 600 participants. The registry will record any surgical treatments used, without dictating specific therapies, allowing individualized clinical decisions. Data collection will cover preoperative, intraoperative, and follow-up details, including the bone defect characteristics and surgical findings. Participants will undergo assessments before and during surgery, with follow-up evaluations at 6 and 12 months, or 6 months after bone healing, up to 18 months. These include functional outcomes, patient quality of life, and radiological imaging. The study will monitor patient progress and outcomes to better understand treatment effects and challenges for those with post-traumatic long bone defects.

Fetal growth restriction FGR affects many pregnancies and is linked to serious risks including stillbirth, preterm birth, and long-term developmental challenges such as cerebral palsy. This trial evaluates whether giving pregnant women melatonin can protect the fetal brain and improve neurodevelopmental outcomes in babies affected by early-onset severe FGR. The study is a triple-blind, randomized, placebo-controlled trial aiming to address the lack of treatments to enhance fetal wellbeing before birth. Participants will receive either melatonin tablets 10 mg three times daily for a total of 30 mg per day or matching placebo tablets three times a day. The trial includes pregnancies diagnosed with severe FGR between 23 and 31 weeks gestation. Treatment continues until birth. The study is conducted across multiple centers, with participant groups randomized based on gestational age to allow sub-analysis of early and late onset FGR. Participants will be monitored throughout pregnancy with assessments of fetal growth and placental blood flow. After birth, childrens neurodevelopment will be evaluated at 2 years of age using the Bayley-IV Cognitive scale. Researchers will also track side effects, maternal organ function, and fetal wellbeing until birth. The total participation duration varies depending on gestational age at enrollment and follow-up visits extend to 2-3 years of the childs life for outcome measurement.

This research aims to compare the effects of oral anticoagulation versus no anticoagulation in patients aged 55 and older who have had recent episodes of transient atrial fibrillation triggered by stress and have additional factors that increase their risk of stroke. The study is a multinational, investigator-initiated, prospective, randomized, open-label trial evaluating the impact of non-vitamin K oral anticoagulants NOACs on preventing stroke and other serious cardiovascular events. Participants will be randomly assigned to either receive one of several NOACs, such as edoxaban, apixaban, dabigatran, or rivaroxaban, prescribed by their physician for the duration of the follow-up, or to a control group that will not receive anticoagulants unless medically indicated during the study. The choice of specific NOAC and dose adjustments are determined by the prescribing doctor. The study excludes patients with certain conditions like chronic atrial fibrillation, severe kidney or liver disease, recent cardiac surgery, or bleeding risks. During the study, participants will be monitored for up to 24 months to assess the occurrence of non-hemorrhagic stroke, systemic embolism, vascular mortality, myocardial infarction, peripheral arterial thrombosis, amputation, and venous thromboembolism. Regular follow-up will include evaluation of these outcomes to measure the effectiveness and safety of anticoagulation compared to no anticoagulation. Participants will provide informed consent and remain under medical supervision throughout the trial.

Researchers are establishing an Australian group of patients diagnosed with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy CADASIL. The study aims to understand the clinical features and how CADASIL progresses over time. It focuses on examining neuropsychological profiles, brain imaging, genetics, blood markers, and retinal imaging to gather comprehensive information about this condition. This observational study is conducted at multiple centers across Australia, including clinics, hospitals, and universities. Participants undergo clinical exams, questionnaires, neuropsychological tests, brain MRI scans, blood sample collection, and retinal imaging. The study includes both individuals with CADASIL and control participants without the genetic variant or cognitive complaints. Participants will complete assessments at the start and annually over four years, including medical questionnaires, cognitive tests, brain scans, blood tests, and eye exams. These evaluations measure cognitive function, physical health, brain changes, and quality of life. Researchers will monitor participants progress over time to better understand CADASIL and its impact.