CENTAUR identifies characteristics of patients with NASH, demonstrates efficacy of cenicriviroc

SAN DIEGO – Data from year 2 of the CENTAUR study demonstrated that cenicriviroc, or CVC, reduced certain biomarkers associated with fibrosis progression compared with placebo, according to findings presented at Digestive Disease Week.

These results build on findings from year 1 of the CENTAUR study that highlighted characteristics of patients with non-alcoholic steatohepatitis who are more likely to experience progression of fibrosis.

“CVC is an oral C-C chemokine receptor type 2/5 antagonist currently being evaluated for the treatment of liver fibrosis in adults with NASH,” the researchers wrote. “In the Phase 2b CENTAUR study, CVC treatment resulted in a significant, durable antifibrotic benefit compared with placebo. The aims of this CENTAUR analysis were to characterize the subpopulation of fibrosis progressors initially treated with placebo during Year 1 compared to fibrosis non-progressors and to evaluate the effect of CVC in fibrosis progressors on histology and biomarkers of fibrosis during Year 2.”

All participants in the study, which was conducted by Nicolas Lanthier, MD, PhD, of the Service d'Hépato-Gastroentérologie at the Cliniques universitaires Saint-Luc, Université catholique de Louvain, in Brussels, and colleagues, were adults with histologically confirmed cases of NASH (nonalcoholic fatty liver disease activity score 4; liver fibrosis stages 1–3 per the NASH Clinical Research Network). Patients in arm A were assigned to receive 150 mg CVC once per day for 2 years; patients in arm C received placebo for 2 years. Patients in arm B were treated with placebo in year 1 and switched to CVC in year 2.

“Fibrosis progressors,” who were categorized as patients who experienced a decline in fibrosis status by one or more stages from baseline to year 1, were identified from the placebo-treated, modified intent-to-treat group (n = 126) in year 1 (arms B and C).

The researchers examined clinical features and serum biomarkers at baseline and over the course of the study. A central pathologist who was blinded to patients’ assigned treatment evaluated histology. The impact of CVC (arm B) vs. placebo (arm C) on patients who experienced fibrosis progression was examined during year 2 of the study.

Among placebo-treated patients in arms B and C from year 1 (n = 126), more than a quarter (29%; n = 37) experienced fibrosis progression. The mean age of these patients was 52.1 years and mean BMI was 34.1 kg/m². Most of these patients (89%) had a NAFLD activity score greater than or equal to 5. Type 2 diabetes was noted in 46% of patients in this group.

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Fibrosis progression occurred more frequently in women (62% vs. 49%) and Hispanic/Latino patients (89% vs. 78%). These patients also had greater disease activity (NAFLD activity score 5, 89% vs. 71%; hepatocellular ballooning grade 2, 65% vs. 51%).

Stage 1 fibrosis at baseline was “considerably” more common among patients who experienced fibrosis progression than in those who did not (65% vs. 20%). Aspartate aminotransferase levels greater than 30 U/L were also more common in “fibrosis progressors” at baseline (89% vs. 74%).

In year 1, increases in serum-transforming growth factor beta and tissue inhibitor of metalloproteinase-1, as well as liver biopsy alpha-smooth muscle actin staining, were more common among patients who experienced fibrosis progression. In year two, CVC treatment correlated with greater levels of tissue inhibitor of metalloproteinase-1. CVC treatment was also associated with decreased alpha-smooth muscle actin staining and decreased serum-transforming growth factor beta concentrations compared with placebo.

“The unique study design of CENTAUR enabled characterization of NASH fibrosis progressors during year 1 and evaluation of the antifibrotic effect of CVC in year 2,” the researchers wrote. “Female sex, ethnicity and inflammatory disease activity are key characteristics of fibrosis progressors. In those [patients], CVC treatment was associated with a reduction of some biomarkers of fibrosis (serum-transforming growth factor beta and alpha-smooth muscle actin staining) vs. placebo in Year 2.”

The findings “warrant further investigation,” the researchers concluded. - by Julia Ernst, MS

Reference:

Lanthier N, et al. Abstract Sa1561. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Lantheir reports consulting roles with Gilead and Promethera Biosciences; grant/research support from AbbVie, MSD and Norgine and speaking and teaching roles with Dr. Falk Pharma and Fresenius Kabi. The abstract was written with assistance from Complete HealthVizion. Please see the abstract for all other authors’ relevant financial disclosures.