US-based Conatus Pharmaceuticals has started a placebo-controlled, double-blind Phase IIb clinical trial of its drug candidate, emricasan for treatment of fibrosis in liver transplant recipients.
The trial is carried out in post-orthotopic liver transplant (POLT) recipients with re-established liver fibrosis post-transplant as a result of recurrent hepatitis C virus (HCV) infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy (POLT-HCV-SVR).
Around 60 patients will be enrolled in the trial at about 15 planned US clinical sites, which is expected to take about 12 months.
In the trial, patients will be randomised 2:1 to receive either 25mg of emricasan or placebo orally twice-daily for 24 months, when they will be followed for another month post-treatment.
The primary endpoint in this exploratory proof-of-concept trial is the change in the Ishak fibrosis score compared with placebo.
The trial will also evaluate histological markers of inflammation, key serum biomarkers, and the safety and tolerability of emricasan in the target patient population.
Conatus president and chief executive officer Steven Mento said the recent introduction of highly successful antiviral treatments has provided new hope for patients infected with HCV but clearance of the virus does not eliminate the damage already established in the liver.
"We believe emricasan may have the potential to accelerate the liver healing process, and this trial is designed to evaluate emricasan’s potential impact on fibrosis," Mento said.
"Proof-of-concept in this patient population could support expansion into additional liver fibrosis indications resulting from viral infections, obesity, chronic excessive alcohol use or autoimmune diseases."
In late-2013, the US Food and Drug Administration (FDA) granted orphan drug designation to emricasan for the treatment of liver transplant recipients with re-established fibrosis to delay the progression to cirrhosis and end-stage liver disease.
Emricasan is being developed to treat chronic liver disease and acute exacerbations of chronic liver disease, including acute-on-chronic liver failure (ACLF), chronic liver failure (CLF), nonalcoholic fatty liver disease (NAFLD), including the subset of NAFLD patients with inflammatory and fibrotic nonalcoholic steatohepatitis (NASH), as well as POLT-HCV-SVR.
The company said that in a completed Phase IIb clinical trial, emricasan consistently showed clinically meaningful, statistically significant, rapid and sustained reductions in elevated levels of two key biomarkers of inflammation and cell death that are implicated in the severity and progression of liver disease.