103 results match your criteria: "Pinnacle Clinical Research[Affiliation]"
Clinical validation of an AI-based pathology tool for scoring of metabolic dysfunction-associated steatohepatitis.
Nat Med
November 2024
PathAI, Inc., Boston, MA, USA.
Article Synopsis
- Metabolic dysfunction-associated steatohepatitis (MASH) is a serious liver condition with limited treatment options and relies on manual biopsies for assessment, which often shows high variability among readers.
- A new artificial intelligence (AI) system, AIM-MASH, has been developed and validated across multiple sites to assist pathologists in scoring liver biopsies related to MASH, showing high reliability and consistency compared to traditional methods.
- AIM-MASH significantly improved the accuracy of assessing key factors like inflammation and MASH resolution when used by expert pathologists, suggesting it can reduce variability and enhance the evaluation of new treatments in MASH clinical trials.
Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial.
Lancet Gastroenterol Hepatol
December 2024
Pinnacle Clinical Research, San Antonio, TX, USA.
Background: Denifanstat, an oral fatty acid synthase (FASN) inhibitor, blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity, inflammation, and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). This study aimed to examine the safety and efficacy of denifanstat for improving liver histology in individuals with MASH and moderate to advanced fibrosis.
Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2b trial was conducted at 100 clinical sites in the USA, Canada, and Poland.
acFibroMASH Index for the Diagnosis of Fibrotic MASH and Prediction of Liver-related Events: An International Multicenter Study.
Clin Gastroenterol Hepatol
October 2024
MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, Zhejiang, China. Electronic address:
Article Synopsis
- Scientists studied a health problem called MASH, which affects people's livers, and worked on two tests to help doctors tell if someone has it.
- They looked at data from over 3,000 people to make sure their first test, called acMASH, worked well, and then created a new test called acFibroMASH to find more severe cases.
- The new acFibroMASH test was better at predicting who might have future liver problems compared to another test, showing it's a useful tool for doctors to keep patients healthy.
Letter to the Editor: Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF).
Hepatology
January 2025
Virginia Commonwealth University Medical Center, Richmond, Virginia, USA.
Use of Resmetirom in Patients With Metabolic Dysfunction-Associated Steatohepatitis.
Gastroenterol Hepatol (N Y)
August 2024
Visiting Professor of Hepatology Radcliffe Department of Medicine, University of Oxford Chairman and Founder, Pinnacle Clinical Research Chairman and Co-Founder, Summit Clinical Research Founder and CEO, Apex Mobile Clinical Research.
Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study.
J Hepatol
January 2025
Altimmune, Inc, Gaithersburg, MD, USA.
Article Synopsis
- A study was conducted to evaluate the impact of pemvidutide, a new medication targeting liver fat content, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) over 12 weeks in a randomized, double-blind, placebo-controlled setting.
- Participants were assigned different doses of pemvidutide (1.2 mg, 1.8 mg, or 2.4 mg) or a placebo, resulting in significant reductions in liver fat content by 46.6%, 68.5%, and 57.1% respectively compared to only 4.4% in the placebo group.
- The highest dose (1.8 mg) also led to
FGF21 agonists: An emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond.
J Hepatol
September 2024
Summit Clinical Research, San Antonio, Texas, USA. Electronic address:
The worldwide epidemics of obesity, hypertriglyceridemia, dyslipidaemia, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) represent a major economic burden on healthcare systems. Patients with at-risk MASH, defined as MASH with moderate or significant fibrosis, are at higher risk of comorbidity/mortality, with a significant risk of cardiovascular diseases and/or major adverse liver outcomes. Despite a high unmet medical need, there is only one drug approved for MASH.
View Article and Find Full Text PDFA Phase 3 Trial of Resmetirom in NASH with Liver Fibrosis. Reply.
N Engl J Med
May 2024
Madrigal Pharmaceuticals, West Conshohocken, PA.
Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease.
JAMA
April 2024
Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis.
Objective: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.
Guideline-based management of metabolic dysfunction-associated steatotic liver disease in the primary care setting.
Postgrad Med
April 2024
Department of Clinical Sciences and Community Health, Touro University California, Vallejo, CA, USA.
Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. Primary care providers play a critical role in the screening, diagnosis, and management of MASLD and/or metabolic dysfunction-associated steatohepatitis (MASH), though they can face challenges in this setting, particularly where healthcare resources are limited and barriers to care exist. To address these challenges, several guidelines have been developed to provide evidence-based recommendations for the clinical assessment and management of patients with MASLD/MASH.
View Article and Find Full Text PDFSafety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study.
Clin Gastroenterol Hepatol
January 2025
Akero Therapeutics Inc, South San Francisco, California.
Background & Aims: In phase 2 studies, efruxifermin, an Fc-FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with non-alcoholic steatohepatitis, now called metabolic dysfunction-associated steatohepatitis (MASH), for which there is no approved treatment. Type 2 diabetes (T2D) and obesity are prevalent among patients with MASH and increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety and efficacy of efruxifermin in patients with MASH, fibrosis, and T2D taking a GLP-1RA.
View Article and Find Full Text PDFThe Emerging Role of Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis.
Clin Gastroenterol Hepatol
August 2024
Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida. Electronic address:
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 1 in 3-4 adult individuals and can progress to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Insulin resistance plays a central role in MASLD/MASH pathophysiology with higher rates of MASLD (2 in 3) and MASH with fibrosis (1 in 5) in adults with obesity and diabetes. This review summarizes the role of glucagon-like peptide-1 receptor agonists in treating MASLD/MASH.
View Article and Find Full Text PDFA Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis.
N Engl J Med
February 2024
From the University of Oxford, Oxford (S.A.H.), the Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne (Q.M.A.), and the National Institute for Health Research, Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham (P.N.N.) - all in the United Kingdom; Pinnacle Clinical Research, San Antonio (S.A.H., M.R.), South Texas Research Institute, Edinburg (R.P.), and Houston Methodist Hospital, Houston Research Institute, Houston (M.N.) - all in Texas; Liverpat and University of Paris (P.B.), INSERM, Unité Mixte de Recherche Scientifique (UMRS) 1139, Centre de Recherche sur l'Inflammation (L.C.), and Sorbonne Université, ICAN Institute for Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris (APHP), INSERM, UMRS 1138, Centre de Recherche des Cordeliers (V.R.), Paris, and Université Paris-Cité, Department of Hepatology, Beaujon Hospital, APHP, Clichy (L.C.) - all in France; Duke University Health System, Durham, NC (C.D.G.); the Metabolic Liver Research Program, I. Department of Medicine, University Medical Center of Johannes Gutenburg University Mainz, Mainz (J.M.S.), the Department of Internal Medicine II, Saarland University Medical Center, Homburg (J.M.S.), and Klinikum St. Georg Leipzig, Leipzig (I.S.) - all in Germany; MASLD Research Center, the Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla (R.L.); Madrigal Pharmaceuticals, West Conshohocken, PA (R.T., D.L.); University of Arizona for Medical Sciences (S.E.M.) and Arizona Liver Health (N.A.) - both in Tucson; Covenant Metabolic Specialists, Sarasota (G.W.N.), and Flourish Research, Boca Raton (S.J.B.) - both in Florida; the Transplant Institute, Department of Medicine, University of Chicago Pritzker School of Medicine, and the Transplant Institute, Center for Liver Diseases, University of Chicago Biological Sciences - both in Chicago (M.E.R., M.R.C.); the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (M.F.A.); the Department of Medicine, Inova Fairfax Medical Campus, Falls Church (Z.Y.), and Virginia Commonwealth University, Richmond (A.J.S.) - both in Virginia; the Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem (S.F.), and Cliniques Universitaires Saint-Luc, Service d'Hépato-gastroentérologie, UCLouvain, Brussels (N.L.) - both in Belgium; the Liver Unit at the IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy (A.M.); the Liver Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona (J.M.P.); and the Division of Liver Diseases, Icahn School of Medicine at Mt. Sinai, New York (M.B.B.).
Article Synopsis
- * A phase 3 trial is underway, where adult participants with confirmed NASH are randomly assigned to receive either resmetirom (80 mg or 100 mg) or a placebo, with primary goals of NASH resolution and improvement in fibrosis after 52 weeks.
- * In the trial's results, a significantly higher percentage of patients taking resmetirom experienced NASH resolution and fibrosis improvement compared to those on placebo, along with notable reductions in cholesterol levels, although some participants did report diarrhea.
Utility of pathologist panels for achieving consensus in NASH histologic scoring in clinical trials: Data from a phase 3 study.
Hepatol Commun
January 2024
Inova Medicine, Inova Healthy System, Falls Church, Virginia, USA.
Background: Liver histopathologic assessment is the accepted surrogate endpoint in NASH trials; however, the scoring of NASH Clinical Research Network (CRN) histologic parameters is limited by intraobserver and interobserver variability. We designed a consensus panel approach to minimize variability when using this scoring system. We assessed agreement between readers, estimated linear weighted kappas between 2 panels, compared them with published pairwise kappa estimates, and addressed how agreement or disagreement might impact the precision and validity of the surrogate efficacy endpoint in NASH trials.
View Article and Find Full Text PDFHyperinsulinemia, an overlooked clue and potential way forward in metabolic dysfunction-associated steatotic liver disease.
Hepatology
December 2023
Research and Development, Cirius Therapeutics, Kalamazoo, Michigan, USA.
Metabolic dysfunction-associated steatotic liver disease is closely associated with other features of the metabolic syndrome such as type 2 diabetes. The progression of the disease may lead to liver fibrosis, which is the main predictor of major adverse liver outcomes. Insulin resistance plays a major role in the pathogenesis of the disease.
View Article and Find Full Text PDFArticle Synopsis
- Nonalcoholic steatohepatitis (NASH) is a serious liver disease that currently has no approved treatments; a recent trial called MAESTRO-NAFLD-1 tested a drug called resmetirom for safety and efficacy in adults with this condition.
- In the 52-week trial involving over 1,000 participants, patients were given different doses of resmetirom or a placebo, and researchers focused on side effects and various health markers like liver fat and cholesterol levels.
- The results showed that resmetirom was generally safe and well tolerated, with reported side effects like diarrhea and nausea, while also leading to significant reductions in liver fat and cholesterol levels compared to placebo, suggesting its potential for further development
Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial.
Lancet Gastroenterol Hepatol
December 2023
Akero Therapeutics, South San Francisco, CA, USA.
Article Synopsis
- The study investigates the safety and efficacy of efruxifermin, a drug that targets the FGF21 pathway, in patients with non-alcoholic steatohepatitis (NASH) and varying degrees of liver fibrosis during a 96-week phase 2b clinical trial.
- Conducted across 41 clinics in the USA, 128 eligible adult participants with confirmed NASH were randomly assigned to receive either efruxifermin (28 mg or 50 mg) or a placebo, with strict masking of group assignments.
- Primary outcomes focused on the proportion of patients experiencing at least a one-stage improvement in liver fibrosis without worsening NASH symptoms, with a total of 747
Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis.
Aliment Pharmacol Ther
January 2024
University of California, San Diego, La Jolla, California, USA.
Article Synopsis
- Non-alcoholic steatohepatitis (NASH) is a severe liver disease that can progress from non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation and liver damage.
- The MAESTRO clinical program includes multiple Phase 3 trials to evaluate the efficacy and safety of resmetirom, a targeted thyroid hormone receptor-β agonist, for treating NASH, with various study designs involving liver biopsies and patient-reported outcomes.
- The goal of these trials is to gather robust evidence to support the approval of resmetirom in treating NASH by assessing both immediate biopsy results and long-term liver health outcomes.
A randomized, double-blind, placebo-controlled trial of aldafermin in patients with NASH and compensated cirrhosis.
Hepatology
March 2024
Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Background And Aims: Aldafermin, an engineered analog of the human hormone FGF19, improves liver histology in patients with noncirrhotic NASH; however, its efficacy and safety in compensated cirrhosis is unknown. No drug has yet to demonstrate benefit in the compensated NASH population.
Approach And Results: In this multicenter, double-blind, placebo-controlled, phase 2b trial, 160 patients with compensated NASH cirrhosis were randomized to aldafermin 0.
Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis.
Aliment Pharmacol Ther
November 2023
Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Article Synopsis
- A clinical study evaluated the effects of pegozafermin, a new therapy, on patients with nonalcoholic steatohepatitis (NASH) and fibrosis to meet an important medical need.
- The study involved adults with specific criteria receiving weekly doses for 20 weeks, measuring improvements in liver condition and safety.
- Results showed significant improvements in liver health and metabolic factors, with most participants tolerating the treatment well, although some experienced mild adverse effects.
Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis.
J Hepatol
November 2023
Beatty Liver and Obesity Research Program, Center for Liver Diseases, Inova Medicine, Falls Church, VA, USA.
Background & Aims: Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from >8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for >4 years.
Methods: Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system.
Background: Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.
Methods: We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers.
Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH.
N Engl J Med
September 2023
From the NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla (R.L.), Velocity Clinical Research, Los Angeles (J.P.F.), and 89bio, San Francisco (M.D.G., S.F., G.D.A., C.L.H., H.M.); the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond (A.J.S.); Liver Institute Northwest, Seattle (K.V.K.); Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York (D.L.B.); Arizona Liver Health, Chandler (N.A.); Liverpat, Paris (P.B.); Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (S.A.H.); Pinnacle Clinical Research, San Antonio, TX (S.A.H.); ObjectiveHealth-Digestive Health Research, Nashville (D.L.); Ocala GI Research, Ocala, FL (R.B.); 89bio, Rehovot, Israel (M.M.); and the Division of Hepatobiliary Disease, Mayo Clinic, Rochester, MN (M.F.A.).
Background: Pegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. The efficacy and safety of pegozafermin in patients with biopsy-proven noncirrhotic NASH are not well established.
Methods: In this phase 2b, multicenter, double-blind, 24-week, randomized, placebo-controlled trial, we randomly assigned patients with biopsy-confirmed NASH and stage F2 or F3 (moderate or severe) fibrosis to receive subcutaneous pegozafermin at a dose of 15 mg or 30 mg weekly or 44 mg once every 2 weeks or placebo weekly or every 2 weeks.
Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study.
Clin Gastroenterol Hepatol
January 2024
Department of Medicine, University of California, San Diego, La Jolla, California.
Background & Aims: Pegbelfermin is a polyethylene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) with compensated cirrhosis.
Methods: FALCON 2 (NCT03486912) was a randomized (1:1:1:1), double-blind, placebo-controlled study.
Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study.
Clin Gastroenterol Hepatol
January 2024
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
Background & Aims: Pegbelfermin is a polyethlene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) and stage 3 (bridging) fibrosis.
Methods: The FALCON 1 study (NCT03486899) was a multicenter, randomized (1:1:1:1), double-blind, placebo-controlled study.