A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis
| العنوان: | A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis |
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| المؤلفون: | Brian L. Wiens, Jeffrey Vest, Guruprasad P. Aithal, Arun J. Sanyal, Star Seyedkazemi, Vincent Wai-Sun Wong, Zachary Goodman, Laurent Fischer, Rohit Loomba, Eric Lefebvre, Vlad Ratziu, Frank Tacke, Kris V. Kowdley, Geoffrey C. Farrell, Manal F. Abdelmalek, Pamela Vig, Liza Melchor-Khan, Antonio Craxì, Scott L. Friedman, Krzysztof Simon, Juan Caballería, Stephen A. Harrison, Sven Francque |
| المساهمون: | Friedman, S., Ratziu, V., Harrison, S., Abdelmalek, M., Aithal, G., Caballeria, J., Francque, S., Farrell, G., Kowdley, K., Craxi, A., Simon, K., Fischer, L., Melchor-Khan, L., Vest, J., Wiens, B., Vig, P., Seyedkazemi, S., Goodman, Z., Wong, V., Loomba, R., Tacke, F., Sanyal, A., Lefebvre, E. |
| المصدر: | Hepatology (Baltimore, Md.), vol 67, iss 5 Hepatology Hepatology (Baltimore, Md.) |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Liver Cirrhosis, Male, Placebo-controlled study, Medical Biochemistry and Metabolomics, Gastroenterology, Oral and gastrointestinal, law.invention, Hepatitis, NASH, NAFLD, CVC, nonalcoholic fatty liver, inflammation, Steatohepatitis/Metabolic Liver Disease, 0302 clinical medicine, Randomized controlled trial, Fibrosis, law, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, education.field_of_study, CVC, Liver Disease, NASH, Imidazoles, Middle Aged, Treatment Outcome, Tolerability, Liver, Sulfoxides, 6.1 Pharmaceuticals, CCR5 Receptor Antagonists, 030211 gastroenterology & hepatology, Original Article, Female, Patient Safety, Adult, medicine.medical_specialty, Population, Chronic Liver Disease and Cirrhosis, Clinical Trials and Supportive Activities, Clinical Sciences, Immunology, Placebo, 03 medical and health sciences, Double-Blind Method, Clinical Research, Internal medicine, NAFLD, medicine, nonalcoholic fatty liver, Humans, education, Aged, Hepatology, Gastroenterology & Hepatology, business.industry, Evaluation of treatments and therapeutic interventions, Original Articles, medicine.disease, equipment and supplies, Surgery, inflammation, 030104 developmental biology, Human medicine, Steatohepatitis, business, Digestive Diseases, Biomarkers |
| الوصف: | The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis. A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score [NAS] ≥4, and liver fibrosis (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of steatohepatitis. Biomarkers of inflammation and adverse events were assessed. Full study recruitment was achieved. The primary end point of NAS improvement in the intent-to-treat population and resolution of steatohepatitis was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144) (16% vs 19%, P = 0.52 and 8% vs 6%, P = 0.49, respectively). However, the fibrosis end point was met in significantly more subjects on CVC than placebo (20% vs 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo. Conclusions: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of steatohepatitis compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation. ClinicalTrials.gov no: NCT02217475 (CENTAUR). This article is protected by copyright. All rights reserved. |
| وصف الملف: | PDF; application/pdf; pdf |
| اللغة: | English |
| تدمد: | 0270-9139 1527-3350 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd279267e63b246d0eb39c5941a3a85bTest https://nottingham-repository.worktribe.com/file/927093/1/Friedman_et_al-2018-Hepatology.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dd279267e63b246d0eb39c5941a3a85b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02709139 15273350 |
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