Nonalcoholic Steatohepatitis (NASH)

Researchers are studying chronic liver diseases and tumors, including non-alcoholic steatohepatitis NASH, non-alcoholic fatty liver disease NAFLD, cirrhosis, and hepatocellular carcinoma HCC. These conditions can be caused by viral infections like hepatitis B, C, and D or lifestyle factors such as overeating and lack of exercise. The goal is to develop better understanding and new treatments by analyzing liver tissues and tumors at the single-cell level to identify therapeutic targets and improve patient outcomes. The study involves creating patient-derived preclinical models, such as spheroid cultures and mouse xenograft models, to test new treatment strategies. Blood samples and tissue biopsies are collected during surgeries, biopsies, or diagnostic tests. Researchers use advanced molecular techniques like single-cell RNA sequencing to examine tumor heterogeneity and the liver environment, aiming to discover new biomarkers and treatment predictors. Participants will undergo procedures as part of their care, including hepato-bilio-pancreatic surgery, biopsies, or locoregional treatments. Blood samples are taken during these procedures to support research. Researchers will monitor surgery outcomes over an average of eight years. By studying patient samples and clinical data, the team aims to improve personalized medicine approaches and identify new preventive and therapeutic targets for chronic liver diseases and liver cancer.

Researchers are evaluating the safety and tolerability of Efimosfermin Alfa in adults with known or suspected metabolic dysfunction-associated steatohepatitis MASH with fibrosis at stages F2 or F3. This phase 3 clinical trial aims to understand how participants respond to this treatment compared to a placebo, focusing on managing this liver condition characterized by metabolic syndrome components and liver fibrosis. Participants will be randomly assigned to one of three groups two groups receiving different dose levels of Efimosfermin Alfa and one group receiving a placebo. The study involves administering the drug or placebo injections over a period of up to 52 weeks. Researchers will monitor participants throughout this time to assess the drugs effects and tolerability. During the study, participants will undergo regular assessments including laboratory tests for liver enzymes and fibrosis markers, imaging tests such as magnetic resonance elastography and MRI-derived fat fraction measurements, and evaluations of metabolic factors like blood sugar and cholesterol. Safety will be closely monitored by tracking adverse events and laboratory abnormalities. The total participation time is about one year, during which participants will have scheduled visits for treatment and evaluation.

Researchers are evaluating whether a new blood biomarker can help identify depression and schizophrenia in patients attending psychiatric clinics. The study aims to see if changes in this biomarker can distinguish depressed patients who respond to treatment from those who do not, and differentiate individuals having a first psychotic episode from those at risk of developing schizophrenia. This observational study involves up to 500 participants grouped by diagnosis into Depression DEP and PsychosisSchizophrenia PSY arms. Participants will attend three study visits over six months, during which blood samples and standard mental health assessments will be collected. These visits will help researchers analyze the relationship between the biomarker characteristics and the mental health conditions. The study does not involve any treatments but focuses on monitoring and measuring the biomarker and clinical factors over time. During the study, participants will complete standardized mental health questionnaires at each visit, and researchers will collect blood samples to study the biomarker changes. The main outcomes measured include the relationship between depression or psychotic disorders and biomarker characteristics over the six-month period. Researchers will also explore how clinical and demographic factors relate to these biomarker changes. The total participation time spans about six months with three scheduled visits.

Researchers are evaluating QX1206 in an open-label phase 1b trial involving adults with Type 2 Diabetes Mellitus T2DM and Non-Alcoholic Fatty Liver Disease NAFLD. The study aims to determine the recommended dose for future studies and examine the preliminary effects of QX1206 on blood sugar control and other metabolic factors. Participants will take QX1206 orally before bedtime. The trial will last up to 12 weeks, during which laboratory tests and measurements will be taken before the first dose and throughout the study to monitor effects and safety. The study focuses on finding the best dose and assessing changes in blood sugar and insulin resistance. During the study, participants will undergo regular assessments including blood tests for hemoglobin A1c, fasting glucose, insulin levels, and insulin resistance. Researchers will track the recommended phase 2 dose from day 1 through week 12. Patients must comply with study procedures and attend all visits. The total participation period is up to 12 weeks.

Researchers are evaluating the study drug ALN-PNP, with and without another drug called tirzepatide, to see if they can help treat Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD, also known as fatty liver disease. ALN-PNP works by reducing a protein called PNPLA3 that liver cells produce, which may decrease liver fat when this protein is abnormal. The goal is to understand the effects of ALN-PNP alone and combined with tirzepatide on reducing liver fat. Participants will receive ALN-PNP with or without tirzepatide, or a placebo matching ALN-PNP, following a randomized and double-blind design. The study includes different groups and is conducted in two parts. Treatments are administered according to the study protocol, and the effects of these drugs on liver fat and other health measures will be compared over time. During the study, participants will be monitored regularly with assessments including liver fat measurements by MRI, blood tests to track drug levels, and safety evaluations to record any side effects. The main outcomes measured are the percentage change in liver fat at 24 and 48 weeks. Additional monitoring of side effects will continue through week 72. The total study duration extends up to March 2030.

Researchers are evaluating efimosfermin alfa in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis MASH and stage F2 or F3 liver fibrosis. The study aims to assess the safety and effectiveness of efimosfermin alfa compared to a placebo in resolving steatohepatitis and improving liver-related clinical outcomes. This Phase 3 trial is randomized, double-blind, and placebo-controlled, focusing on participants with specific liver conditions and metabolic syndrome components. Participants are assigned to one of three groups two groups receive different dose levels of efimosfermin alfa, while the third group receives a placebo. Treatments are given under controlled conditions, and the study follows a parallel design. The trial monitors participants at set intervals over a course of 52 weeks, with some outcomes tracked up to 48 months to evaluate long-term effects on liver fibrosis and steatohepatitis. During the study, participants undergo liver biopsies to confirm diagnosis and assess changes. Researchers evaluate improvements in fibrosis stage, steatohepatitis resolution, and various liver function measurements using imaging and blood tests. Safety is monitored by tracking adverse events and laboratory abnormalities. Quality of life and other health indicators are also assessed throughout the study, which lasts several years to capture both short- and long-term outcomes.

Researchers are studying an investigational drug called ALN-HSD in adults with Metabolic Dysfunction-Associated SteatoHepatitis MASH, a liver condition caused by fat buildup that damages liver cells and causes inflammation and scarring. This condition can worsen to cirrhosis and liver failure. The study aims to evaluate how ALN-HSD affects liver scarring related to MASH and to understand its impact on liver function and inflammation, as well as potential side effects and how the drug is processed in the body. Participants will be randomly assigned to receive either ALN-HSD or a placebo in a double-blind setup. The study involves a 52-week treatment period during which the effects of ALN-HSD on liver fibrosis and other liver-related biomarkers will be assessed. The trial includes genetic risk factor screening for enrollment and collects data on drug levels and metabolites. Treatment is administered according to the study protocol, with monitoring continuing through week 84 for adverse events. Throughout the study, participants will undergo liver biopsies and various laboratory tests to measure liver fibrosis, enzyme levels, and other biomarkers related to MASH. Researchers will track changes from baseline to week 52 in liver fibrosis and inflammation, along with monitoring adverse events until week 84. Participants are involved in regular assessments to evaluate the study drugs impact on their liver health over the course of the trial.

This research aims to better understand metabolic dysfunction-associated fatty liver disease MAFLD, a condition defined by fatty liver with metabolic risks like obesity, diabetes, or metabolic problems. The study also seeks to compare MAFLD with non-alcoholic fatty liver disease NAFLD, including patients who have liver fat but no metabolic risk, and those with both MAFLD and other liver diseases. The goal is to clarify clinical features and improve diagnosis and outcomes for these patients. The study includes two parts first, a cross-sectional analysis collecting clinical data from patients with fatty liver to examine their characteristics second, a long-term follow-up involving collection of plasma, urine, and stool samples to identify biomarkers that help predict disease progression and patient stratification. The trial will observe patients over time to assess these factors. Participants will undergo clinical data collection and sample provision, with researchers monitoring for outcomes such as all-cause death over 10 years. They will also track liver-related complications and other important health issues like cardiovascular disease. The study aims to understand how different metabolic factors relate to disease progression. This long-term observational approach will provide insights to inform better management of MAFLD and NAFLD.

Researchers are evaluating the effectiveness of bariatric surgery compared to standard medical treatment in obese patients with nonalcoholic steatohepatitis NASH complicated by advanced liver fibrosis grades F3 and F4. This study aims to show whether bariatric surgery leads to the disappearance of NASH without worsening fibrosis in patients with a body mass index BMI between 30 and 35 kgm for F3 fibrosis, and between 30 and 50 kgm for F4 fibrosis. The trial is open-label and randomized, designed to compare surgical intervention with lifestyle therapy.

Researchers are evaluating the safety and tolerability of a new medicine called NNC4005-0001 in adults who have increased body weight and liver fat, specifically those with fatty liver disease. This early phase 1 clinical trial aims to understand how the medicine behaves in the body and whether it causes any side effects. The study is sponsored by Novo Nordisk AS and is designed as a randomized, double-blind, placebo-controlled trial to ensure reliable results. Participants will receive a single injection of either NNC4005-0001 or a matching placebo under the skin. The trial includes up to six groups with increasing doses of the medicine to assess its effects at different levels. Each participant will only receive one dose, and the study will monitor them closely for about 7 to 8 months. During the study, participants will have various assessments to track safety and how the medicine is processed in the body. Researchers will record any side effects from the day of dosing until the end of the study visit on day 169. Blood samples will be taken to measure the concentration of the medicine over time, including the highest level reached and how quickly it is cleared from the body. The study involves regular visits and evaluations to ensure participant safety and gather important information about the treatment.