Primary Biliary Cholangitis (PBC)

Researchers are evaluating the use of elafibranor in adults with Primary Biliary Cholangitis (PBC) who also have cirrhosis, a serious liver condition involving scarring. PBC is a slowly progressing disease that damages bile ducts, causing bile acids to build up and harm the liver further. This study aims to see if elafibranor can better prevent worsening of the disease, including the need for liver transplant or death, compared to a placebo. The safety of long-term use and effects on symptoms like itching and tiredness will also be assessed. Participants will be randomly assigned to take either one 80 mg tablet of elafibranor or a matching placebo tablet once daily, taken orally with or without food, at about the same time each morning. The treatment period can last up to 3.5 years in a double-blind setting, meaning neither participants nor researchers know who receives the drug or placebo. This design allows a direct comparison of elafibranor's impact on disease progression and safety over a long term. Throughout the study, participants will undergo regular assessments including blood tests, physical exams, vital signs, ECGs, and liver imaging to monitor liver function and stiffness. Researchers will track a range of outcomes such as survival without clinical events, changes in liver and blood markers, symptom severity, and quality of life measures. Safety monitoring will continue until 4 weeks after the last dose. Each participant may be involved for up to 3.5 years from baseline to final evaluation.

Researchers are investigating the use of 18F-DFA PET imaging to evaluate liver injury, a condition involving rapid liver function decline with symptoms like increased liver enzymes, jaundice, and abdominal discomfort. This observational study aims to assess how accurately this imaging method detects liver damage compared to standard clinical biochemical tests and liver biopsy, which is the current gold standard despite its sampling limitations. The study focuses on adults clinically diagnosed with liver damage or liver failure, exploring the correlation between 18F-DFA uptake in the liver and liver function indicators. Participants diagnosed with liver injury will undergo 18F-DFA PET imaging as part of the study. This radioactive tracer, based on vitamin C structure, is used to visualize liver function non-invasively. The imaging process involves a PET-CT scan lasting about 10 minutes, followed by a one-hour waiting period in the examination room before leaving. The study will compare imaging results with clinical liver function tests or liver biopsy findings to determine the sensitivity and specificity of this method. During the study, participants will have their liver function monitored using PET-CT scans and clinical biochemical markers. The primary outcomes include changes in liver uptake values on PET imaging at 6 months and the relationship between imaging results and standard liver function indicators. Participants will be followed up as needed, with assessments including liver enzyme levels and other blood tests. The total study duration depends on individual follow-up, and safety monitoring will address any issues related to PET imaging procedures.

Researchers are observing the real-world use of the drug elafibranor in people with Primary Biliary Cholangitis (PBC), a rare progressive liver disease where bile ducts are damaged. This damage can cause liver scarring and symptoms like itching and fatigue. The study aims to collect information on how effective, safe, and tolerable elafibranor is for PBC patients receiving ongoing treatment. Each participant will be part of the study for about 5 years. Participants will continue their treatment with elafibranor as prescribed by their doctors while researchers gather data without altering care. The study monitors participants over a 60-month period, collecting information during routine physician follow-up visits. There is no placebo or comparison group since this is an observational study focusing on real-world use of elafibranor. During the study, researchers will track treatment response at 6 months and follow liver function tests, symptom changes like itching and fatigue, quality of life, liver stiffness, and safety measures up to 5 years. They will also assess participant satisfaction and adherence to treatment. Data is collected during regular medical visits, making participation flexible and integrated with usual care.

Researchers are evaluating the effectiveness and safety of a drug called CS0159 in adults with Primary Biliary Cholangitis (PBC) who have an inadequate response or cannot tolerate ursodeoxycholic acid (UDCA). This Phase III trial is randomized, double-blind, and placebo-controlled, aiming to improve treatment options for PBC patients with limited success from existing therapies. Participants will be randomly assigned in a 2:1 ratio to receive either 4 mg of CS0159 or a placebo once daily for up to 52 weeks. Those already taking UDCA may continue their stable dose if applicable. The study compares CS0159 to placebo to assess its impact over this one-year period. During the trial, participants will undergo regular monitoring including laboratory tests to measure liver enzymes and other health markers. Researchers will track response to treatment, adverse events, and clinical outcomes up to 56 weeks. The main goal is to measure how many patients meet specific response criteria at week 52, with ongoing safety assessments throughout the study period.

Researchers are evaluating how nemtabrutinib, a drug given by mouth, behaves in the blood (pharmacokinetics) after a single dose in people with moderate liver impairment compared to healthy individuals. The study also aims to assess the safety and tolerability of nemtabrutinib in these participants. This is a Phase 1 clinical trial sponsored by Merck Sharp & Dohme LLC. Participants with moderate hepatic impairment and healthy matched controls each receive one oral dose of 25 mg nemtabrutinib on Day 1. The study groups include those with moderate liver impairment classified by specific medical criteria and healthy volunteers. Both groups receive the same dosage and form of the drug. Participants will have multiple blood samples taken before and at various times up to 336 hours after dosing to measure drug levels and related pharmacokinetic parameters. Safety is monitored through adverse event reports up to about 15 days. The total study duration includes dosing and follow-up assessments to evaluate how the drug is processed and tolerated in the body.

Researchers are evaluating the safety of siplizumab, an investigational anti-CD2 monoclonal antibody, as an induction immunosuppressive treatment in adult patients with autoimmune liver diseases (AILD) such as autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) undergoing liver transplantation. This pilot, open-label phase 1 study addresses the need for effective therapies to prevent immune-mediated graft injury and complications post-transplant. Siplizumab targets memory T cells involved in rejection and autoimmunity after liver transplantation in these patients. Participants will receive two intravenous doses of siplizumab at 0.6 mg/kg: one dose intraoperatively on the day of transplant (Day 0) and another on Day 4 post-transplant. Up to eight subjects will be enrolled. The study lasts about 15 months, including approximately three months waiting for transplant and 12 months of follow-up after transplantation. During the study, participants will be monitored for serious infections within the first month after transplant and for other outcomes such as immune-mediated liver injury, graft loss or death, rejection episodes, donor-specific antibodies, and disease recurrence over 12 months post-transplant. Assessments will include safety, tolerability, pharmacokinetics, and pharmacodynamics of siplizumab, with ongoing observation throughout the study period.

Researchers are investigating the relationship between the volume of normal liver tissue removed during surgery, called resected normal liver parenchymal volume (RNLV), and the risk of liver failure after liver surgery (post-hepatetotomy liver failure, or PHLF). This observational study focuses on patients diagnosed with hepatocellular carcinoma (HCC) or intracholangiocarcinoma (ICC) who have undergone liver resection. The goal is to build and assess a personalized predictive model using RNLV to better estimate the risk of PHLF before surgery. The study collects data retrospectively from over a thousand patients treated at the investigator’s center. Patients are grouped based on whether they developed liver failure after surgery, defined by two sets of criteria known as the 50-50 criteria and ISGLS criteria. The research evaluates how well the RNLV-based model predicts PHLF and compares its usefulness to other methods, especially for patients with large or multiple liver tumors. Participants' medical records and surgical details are reviewed to calculate RNLV and assess liver failure outcomes within 30 days after surgery. The main outcome is the predicted probability of PHLF using the newly developed model. This approach aims to improve preoperative risk assessment to support safer liver surgeries. The study is sponsored by the National Natural Science Foundation of China and runs through the end of 2026.

Researchers are studying EDG-7500 to understand how it behaves in the blood after a single dose in adults with different levels of liver function, including those with normal liver function and those with mild or moderate hepatic impairment. This Phase 1 trial also evaluates the safety of EDG-7500 in these groups to see how liver impairment affects the drug's presence and tolerability. Participants receive one oral dose of EDG-7500. The study includes three groups: healthy adults with normal liver function, adults with mild hepatic impairment, and adults with moderate hepatic impairment. The trial is open-label, meaning all participants know they are receiving EDG-7500. There are no placebo groups or blinding methods used. During the study, researchers monitor the amount of EDG-7500 in the blood over time, up to 10 days after dosing, measuring key levels such as maximum concentration and overall exposure. Safety is also tracked by observing any treatment-related side effects for up to 14 days. Participants undergo health assessments including blood tests, vital signs, and heart monitoring to ensure safety throughout the study timeline, which starts with screening and continues through follow-up.

Researchers are evaluating the investigational drug volixibat for treating itching (pruritus) caused by Primary Biliary Cholangitis (PBC), a liver disease. This Phase 2 clinical trial aims to learn more about volixibat's effects on itching and its potential impact on PBC disease progression. The study is sponsored by Mirum Pharmaceuticals, Inc. Participants are randomly assigned to one of several groups receiving either volixibat capsules at doses of 20mg or 80mg twice daily, or placebo capsules without the active drug, also taken twice daily. The trial includes two parts, with some participants receiving volixibat 20mg twice daily and others receiving matching placebo capsules. The study is double-blind, meaning neither participants nor researchers know which treatment is given. During the study, participants' itching levels are monitored using the Adult Itch Reported Outcome questionnaire over 28 weeks. Researchers also assess quality of life, fatigue, sleep disturbance, liver function tests, bile acid levels, and adverse events. Participants will attend regular visits for assessments, and the main outcome measured is the change in daily itch scores from baseline to week 28. The study excludes healthy volunteers and focuses on adults aged 18 years and older with confirmed PBC.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and preliminary effectiveness of two dose levels of golexanolone compared with placebo in adults with Primary Biliary Cholangitis (PBC) who experience significant fatigue and cognitive symptoms. This study includes subjects with non-cirrhotic or Child-Pugh class A cirrhotic PBC who are on stable standard of care medication. The study is conducted in two parts, a phase 1b/2 randomized, double-blind, placebo-controlled trial designed to explore these outcomes.