Biopharmaceutical company Tobira Therapeutics has reported positive results from a Phase l study of cenicriviroc (CVC) in patients with liver cirrhosis and mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.
Taken once a day, CVC is an oral, potent immunomodulator that blocks the CCR2 and CCR5 chemokine receptors, which are involved in the inflammatory and fibrogenic pathways in non-alcoholic steatohepatitis (NASH) disease, which causes liver damage and often lead to cirrhosis, liver cancer or liver failure.
The drug is currently being evaluated in Tobira's fully enrolled global Phase llb CENTAUR study and the company expects to announce the study's primary endpoint in the third quarter of this year.
CENTAUR is comparing CVC to placebo in 289 patients with NASH and liver fibrosis.
More than 600 subjects have so far been dosed in completed studies with CVC, including 115 HIV infected subjects on treatment for up to 48 weeks.
The open-label, non-randomised, single-centre Phase I study was conducted in the US and enrolled participants with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, as well as healthy participants with normal hepatic function were matched for age, body weight and gender.
Tobira noted that the study includes two cohorts, namely participants with mild hepatic impairment and their matched controls with normal hepatic function; and participants with moderate hepatic impairment and their matched controls with normal hepatic function.
Both cohorts were conducted in parallel.
The study evaluated the pharmacokinetics, pharmacodynamics and safety of CVC in patients with cirrhosis and mild or moderate hepatic impairment compared with healthy matched controls.
After once-daily administration of CVC 150mg over 14 days, participants with mild hepatic impairment did not have increased exposures whereas those with moderate hepatic impairment had higher exposures.
Exploratory analyses to evaluate pharmacodynamic effects of CVC on CCR2 and CCR5, proinflammatory cytokines and bacterial translocation biomarkers did not disclose any significant differences between participants with hepatic impairment and those with normal hepatic function.
Besides, CVC was generally well tolerated, with adverse events consistent with its known safety profile.
CVC treatment led to rapid and reciprocal increases in CCL2 and CCL5, consistent with potent and sustained CCR2/CCR5 blockade across all treatment groups.
Despite increases in CCL2 and CCL5, no significant effects on markers of hepatic inflammation or proinflammatory cytokines were seen over the 14-day treatment period of the trial.