In:
American Journal of Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 114, No. 1 ( 2019-10), p. S1601-S1602
Abstract:
CVC, a novel, oral, and potent inhibitor of C-C chemokine receptor types 2 and 5, was well tolerated and demonstrated clinically meaningful antifibrotic activity in a 2-year Phase 2b study. The AURORA Phase 3 study will assess the efficacy and safety of CVC for the treatment of liver fibrosis in adults with NASH. METHODS: AURORA is a global, multicenter, randomized, double-blind, placebo-controlled study (NCT03028740) which will enroll 2000 subjects to evaluate a surrogate histology endpoint in the first 1200 subjects and clinical outcomes in the totality of enrolled subjects (∼2000 subjects) (Figure 1). Subjects will be randomized 2:1 to receive CVC 150 mg or placebo orally once daily with food. Adults aged 18–75 years with histologic diagnosis of NASH and Stage 2 or 3 liver fibrosis per NASH Clinical Research Network classification will be enrolled (≥60% with Stage 3). Subjects with cirrhosis or other known causes of chronic liver disease will be excluded. Liver biopsies will be performed at screening and Months 12 and 60 and will be evaluated by a central pathologist. An online tool (AURORA Toolbox) was developed to help assess the individual risk of fibrotic NASH (low, intermediate, or high) to inform pre-screening and whether to conduct a new liver biopsy during screening. RESULTS: The primary endpoint of improvement in fibrosis by ≥1 stage (NASH Clinical Research Network) AND no worsening of NASH (lobular inflammation or hepatocellular ballooning) on liver histology at Month 12 relative to screening biopsy will be evaluated in the first 1200 enrolled subjects. The key secondary endpoint will be improvement in fibrosis by ≥2 stages AND no worsening of NASH. Another primary endpoint to be evaluated in all 2000 enrolled subjects will be time to first occurrence of any adjudicated events of mortality (all causes), progression to cirrhosis (defined by NASH fibrosis Stage 4), liver transplant, Model for End-Stage Liver Disease score ≥15, ascites, or liver decompensation. The study will be terminated when adjudicated events have been accrued in 367 unique subjects overall. Safety, patient-reported outcome measures, serum hepatic fibrosis indices, liver stiffness measure, and biomarkers of systemic inflammation will also be evaluated. CONCLUSION: The AURORA Phase 3 study aims to confirm the efficacy and safety of CVC for the treatment of liver fibrosis in adults with NASH.
Type of Medium:
Online Resource
ISSN:
0002-9270
,
1572-0241
DOI:
10.14309/01.ajg.0000601300.34038.4b
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2019
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