Cenicriviroc for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis: AURORA Phase 3 study design

• Published in: Contemporary clinical trials Vol. 89; p. 105922
• Main Authors: Anstee, Quentin M., Neuschwander-Tetri, Brent A., Wong, Vincent Wai-Sun, Abdelmalek, Manal F., Younossi, Zobair M., Yuan, Jiacheng, Pecoraro, Maria Lucia, Seyedkazemi, Star, Fischer, Laurent, Bedossa, Pierre, Goodman, Zachary, Alkhouri, Naim, Tacke, Frank, Sanyal, Arun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• Subjects: Adolescent; Adult; Aged; Cenicriviroc; Clinical Trials, Phase III as Topic; Disease Progression; Double-Blind Method; Female; Humans; Imidazoles - therapeutic use; Liver Cirrhosis - drug therapy; Liver Cirrhosis - etiology; Liver Cirrhosis - pathology; Liver fibrosis; Male; Middle Aged; Multicenter Studies as Topic; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - pathology; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Randomized Controlled Trials as Topic; Receptors, CCR - antagonists & inhibitors; Research Design; Severity of Illness Index; Sulfoxides - therapeutic use; Young Adult; NAS; T2DM; NAFLD; Cenicriviroc; ITT; ALT; Liver fibrosis; mITT; WPAI-NASH; Nonalcoholic steatohepatitis; ULN; Nonalcoholic fatty liver disease; NASH CRN; AST; AE; CI; NASH; CLDQ-NAFLD-NASH; SF-36; CVC; CCR; HIV; MELD; NCI; APRI; FIB-4
• ISSN: 1551-7144; 1559-2030; 1559-2030
• DOI: 10.1016/j.cct.2019.105922

Nonalcoholic steatohepatitis (NASH) is a sub-classification of nonalcoholic fatty liver disease (NAFLD) characterized by increased risk of progressive liver fibrosis. Cenicriviroc (CVC) is a novel, orally administered, potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with NASH. Efficacy and safety of CVC will be comprehensively evaluated in a global, Phase 3, multicenter, randomized, double-blind, placebo-controlled study (AURORA, NCT03028740) of subjects with NASH and Stage F2 or F3 fibrosis. Approximately 2000 adults (Part 1, 1200 subjects; Part 2, 800 additional subjects) aged 18–75 years with histological evidence of NASH with Stage F2 or F3 fibrosis (NASH Clinical Research Network classification system) will be randomized 2:1 to CVC 150 mg or placebo orally once daily. Primary efficacy endpoints will include the proportion of subjects with ≥1-stage improvement in liver fibrosis and no worsening of steatohepatitis at Month 12 relative to screening (Part 1), and time to first occurrence of any adjudicated event: death; histopathologic progression to cirrhosis; liver transplant; Model of End-Stage Liver Disease score ≥ 15; ascites; hospitalization due to liver decompensation (Part 2). Patient-reported outcomes will assess changes in health outcomes from baseline (Chronic Liver Disease Questionnaire - NAFLD; Work Productivity and Activity Impairment in NASH; 36-Item Short Form Health Survey version 2). Adverse events will be assessed throughout the study. As there are currently no approved treatments indicated for NASH, the AURORA CVC Phase 3 study addresses an unmet medical need.