The U.S. Food and Drug Administration (FDA) has granted investigational new drug (IND) status to GKT831, allowing French pharmaceutical company Genkyotex to advance its drug to a Phase 2 clinical trial in patients with primary biliary cholangitis. The trial will likely begin by September 2017, with full results expected in late 2018.
In preclinical studies with multiple rodent models of liver disease, treatment with GKT831 — which inhibits NOX1 and NOX4 enzymes — showed significant anti-inflammatory and anti-fibrotic effects. In addition, it significantly reduced markers of inflammation and liver injury in patients with type 2 diabetes.
The new Phase 2 multicenter, double-blind, placebo-controlled trial will enroll 102 primary biliary cholangitis patients who responded poorly to ursodeoxycholic acid. Over a 24-week period, they will be randomly assigned to either a placebo or one of two doses of GKT831 (400 mg once a day or 400 mg twice a day). Researchers will evaluate the drug’s safety and efficacy.
Primary biliary cholangitis, also known as primary biliary cirrhosis, is a chronic liver disease characterized by a progressive destruction of the liver’s intrahepatic bile ducts. Bile produced by the liver travels to the small intestine via the intrahepatic bile ducts, helping to digest of fat and fat-soluble vitamins (A, D, E and K). When those ducts are destroyed, bile builds up in the liver, causing inflammation and scarring, or fibrosis.
The study aims mainly to determine how well GKT831 reduces liver injury by using a marker called gamma glutamyl transpeptidase. Secondary endpoints include the drug’s effect on markers of liver inflammation and injury (ALT, CK-18, hs-CRP), and non-invasive markers of liver fibrosis such as the Enhanced Liver Fibrosis score, circulating collagen fragments and transient elastography.
“FDA clearance of our IND application is an important milestone for Genkyotex,” CEO Elias Papatheodorou said in a press release. “We are continuing with preparations aimed at initiating our Phase 2 trial at over 50 investigational centers in North America and Europe. Demonstrating the clinical efficacy of GKT831 in fibrotic liver disease is our primary objective in this study.”