iTherX, a pharmaceutical company dedicated to discovering and developing a new class of therapies for hepatitis C, announced that it has commenced patient recruitment in an open-label, proof-of-concept phase I b study of its lead compound ITX-5061 in liver transplant patients with Hepatitis C Virus infection (HCV). ITX-5061 represents a first-in-class compound that inhibits entry of the hepatitis C virus into liver cells.

“ITX-5061 possesses a unique mechanism of action that prevents the hepatitis C virus from entering liver cells and has demonstrated potent preclinical antiviral activity against all HCV genotypes. In addition, it has already demonstrated safety in more than 280 subjects,” said Jeffrey McKelvy, MD, PhD, president and chief executive officer of iTherX. “We hope ITX-5061 will significantly improve long-term transplant outcomes.”

The primary objective of the phase 1b clinical trial will be to assess the safety and tolerability of ITX-5061 in liver transplant patients. The study will also assess HCV viral load for three months after liver transplantation to determine if ITX-5061 has any immediate and/or sustained impact on viral kinetics in treated patients. Approximately 20 patients will be enrolled into one of two cohorts: one group will receive supportive care only, while the second cohort will also receive ITX-5061 at a 150 mg daily dose for seven days. The trial is being conducted at the University of Birmingham, UK under the direction of David Mutimer, MBBS, MD, FRACP, FRCP, Reader in Hepatology at Birmingham University and Consultant Hepatologist to the Birmingham QE Hospital Liver and Hepatobiliary Unit.

Preclinical studies have shown ITX-5061 to be a potent and selective inhibitor of HCV entry into hepatocytes, capable of preventing virus binding/fusion and cell to cell spread, suggesting ITX-5061 may reduce re-infection rates following liver transplant.

“Recurrence of HCV infection among liver transplant patients is universal and immediate. Clinicians have long sought ways to prevent re-infection by HCV, improve transplant patient outcomes and extend survival,” said Dr Mutimer. “The potential of ITX-5061 to prevent or reduce viral infection of the new liver by halting viral-entry into healthy cells represents an extraordinarily novel approach, and we are excited to advance the clinical development of this promising antiviral compound.”

The phase I b trial of ITX-5061 in liver transplant recipients is funded through an educational grant from iTherX with the National Institute of Health Research Biomedical Research Unit (NIH-BRU Birmingham).

This is a second clinical study for ITX-5061 in hepatitis C. The first study, a single agent placebo-controlled dose response study commenced in August 2010, is being conducted in treatment naïve chronic HCV patients by the AIDS Clinical Trial Group of the National Institute of Allergy and Infectious Diseases.

Hepatitis C Virus (HCV) infection, a disease that attacks the liver, affects 170 million people worldwide. The majority of individuals develop chronic infection and up to 20 percent of infected individuals will develop cirrhosis with the attendant risks of liver failure and liver cell cancer. The current standard of care is combination antiviral treatment with pegylated interferon-alpha and ribavirin, which results in a cure for approximately half of all patients.

Unfortunately, many patients present with clinically silent infection or advanced disease, at which time antiviral treatment is generally ineffective. For these patients, liver transplantation may be the only option. End-stage liver disease due to chronic HCV infection has become the leading indication for liver transplantation in the United States. Recurrence of hepatitis C virus after liver transplantation is inevitable and disease progression is rapid when compared with disease in the non-transplanted liver.

iTherX is a pharmaceutical company focused on the discovery and development of a novel class of antiviral therapeutics that act by blocking entry of the hepatitis C virus into liver cells to halt the spread of infection.