Primary Biliary Cholangitis (PBC)

This research aims to evaluate elafibranor, a study drug, compared to a placebo in adults with Primary Biliary Cholangitis PBC and cirrhosis, a liver disease causing bile duct damage and scarring. The trial focuses on whether elafibranor can better prevent worsening of the disease, including progression leading to liver transplant or death, and also assesses long-term safety and symptom impact such as itching and tiredness. Participants will be randomly assigned to take either an 80 mg tablet of elafibranor or a matching placebo tablet once daily, orally, with or without food. This double-blind treatment period can last up to 3.5 years for each participant, with tablets taken at approximately the same time each morning. The study is designed to compare these two groups over the long term. During the study, participants will undergo regular assessments including physical exams, vital signs, electrocardiograms, laboratory tests, and symptom questionnaires at intervals up to 3.5 years. Researchers will measure liver function tests, symptom scales, liver stiffness, and clinical outcomes related to disease progression. Safety is monitored through adverse event tracking and laboratory parameters, with follow-up extending to four weeks after the last dose. Overall participation may last up to 3.5 years.

Researchers are studying how the drug D-2570 is processed in the body and its safety in adults who have liver problems compared to those with normal liver function. This single-center, non-randomized, open-label study evaluates the pharmacokinetic profile of D-2570, focusing on how the drug moves through the body in different participants. The study includes adults aged 18 to 70 years, both with hepatic impairment and healthy liver function. Participants receive a single oral dose of D-2570 during the study. The study is organized into parallel groups, with participants with liver impairment enrolled first, followed by those with normal liver function. Researchers will monitor how the drug is absorbed, distributed, metabolized, and cleared, using blood samples collected up to 192 hours after dosing. During participation, individuals will undergo assessments to measure drug levels and safety, including monitoring for adverse events up to 9 days after dosing. The study tracks several key pharmacokinetic parameters such as time to maximum plasma concentration, maximum concentration, half-life, area under the curve, clearance, and volume of distribution. The entire study is expected to conclude by November 2026, with a primary completion date in October 2026.

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 use of the drug elafibranor in people with Primary Biliary Cholangitis PBC, a rare progressive liver disease that damages bile ducts and can lead to liver scarring. The study aims to collect real-world information on how effective, safe, and tolerable elafibranor is for participants receiving this treatment. The total participation lasts about 5 years for each person. Participants in the study are those who have been diagnosed with PBC and are either starting or currently receiving treatment with the commercialized drug elafibranor. The study does not intervene with treatment but monitors participants as they use the drug in routine care. Data is collected during regular physician follow-up visits over the 60-month period. During the study, researchers will assess response to treatment at 6 months and continue monitoring various health measures such as liver function tests, symptom scales for itching and fatigue, quality of life questionnaires, and liver stiffness. They will also track adverse events, treatment satisfaction, and adherence throughout the study. Follow-up is based on routine medical visits, with no extra visits required specifically for the study.

Researchers are evaluating the drug CS0159 in a Phase III clinical trial for patients with Primary Biliary Cholangitis PBC who have an inadequate response or intolerance to ursodeoxycholic acid UDCA. This randomized, double-blind, placebo-controlled study aims to assess the efficacy and safety of CS0159 in this population. The study involves approximately 135 participants and is sponsored by Cascade Pharmaceuticals, Inc. Participants will be randomly assigned in a 21 ratio to receive either 4 mg of CS0159 or a placebo once daily for up to 52 weeks. Participants who are already taking UDCA should continue their stable dose during the study if applicable. The study compares the effects of CS0159 against placebo while monitoring participants over one year. During the study, participants will undergo various assessments including laboratory tests to monitor liver function and safety. Researchers will measure the proportion of patients achieving a composite response at 52 weeks as the primary outcome. Secondary outcomes include normalization of liver enzymes and monitoring of adverse events. The total participation period lasts up to 52 weeks, with ongoing safety monitoring throughout the trial.

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 mgkg 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 investigators 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 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 volixibats 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, and initial effects of two dosages of golexanolone compared to placebo in adults with Primary Biliary Cholangitis PBC who experience significant fatigue and cognitive symptoms. This phase 1b2 randomized, double-blind, placebo-controlled study focuses on patients with non-cirrhotic or mild cirrhotic PBC Child-Pugh class A who are on stable standard care medication. The study aims to understand how golexanolone affects fatigue, daytime sleepiness, cognitive function, and overall quality of life. The study has two parts Part A assesses safety, tolerability, and pharmacokinetics of golexanolone 40 mg taken twice daily for 5 days. Part B evaluates safety, tolerability, and effects of two dose levels 40 mg and 80 mg, twice daily compared to placebo over 28 days. Participants receive soft gelatin capsules orally twice daily during these periods. The study uses a parallel design with randomized allocation and quadruple masking to compare golexanolone doses and placebo. Participants will be monitored from enrollment through 5 days in Part A and 28 days in Part B, with assessments including adverse event tracking, quality of life questionnaires PBC-40, EQ-5D-3L, sleepiness scales, cognitive tests, and investigator impressions of treatment effect. Pharmacokinetic sampling occurs on days 1, 14, and 28 in Part B. Safety and tolerability are closely observed, with the total participation lasting up to 28 days depending on the part enrolled.

Chronic liver diseases affect over 800 million people worldwide and cause about 2 million deaths each year. Early diagnosis and prediction of disease progression remain major challenges, as current blood markers and panel tests lack sensitivity and specificity. This research focuses on albumin post-translational modifications PTM as potential early biomarkers that may indicate future liver damage and help predict disease progression in patients with chronic liver disease. The study will recruit 756 patients with compensated fibrosis from six university hospitals and follow them for up to three years. Blood samples will be taken at the start and during follow-up visits at one, two, and three years, either through additional tubes added to routine samples or using leftover samples. These will be analyzed centrally to assess albumin isoform profiles and ligand-binding capacities using the Serum Enhanced Binding SEB test. Participants will have no extra visits beyond their usual care appointments. Data including blood results and medical records will be collected at each visit. Researchers will evaluate the ability of albumin modifications and the SEB test to predict liver disease progression, monitor changes over time, and confirm characteristic albumin patterns related to liver injury. The study aims to improve liver disease diagnostics and patient care by validating these novel biomarkers.