Conatus Pharmaceuticals, a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease, has initiated active patient recruitment in a phase IIb clinical trial of emricasan in patients with acute-on-chronic liver failure (ACLF).
The placebo-controlled, double-blind, multi-centre clinical trial is designed to assess the pharmacokinetics and pharmacodynamics of emricasan in patients who have compensated or stable liver cirrhosis and who, at the time of study entry have been hospitalized for at least 24 hours due to acute deterioration of liver function.
"This study marks an important milestone in the development of emricasan and we are excited about the potential of emricasan to address this underserved population in high medical need of an efficacious and well-tolerated therapy to prevent progression to multi-organ failure and, ultimately, premature death," said Dr Gary C Burgess, chief medical officer of Conatus.
Conatus plans to use this trial to determine the dose of emricasan to be studied in the planned phase III trial in ACLF. Safety of emricasan in the patient population will be evaluated, and key biomarkers and clinical outcomes will also be explored. The phase IIb trial is being conducted at approximately 15 centres in the United Kingdom.
There are currently no approved therapies with a specific indication for the treatment of ACLF, which occurs in patients who have compensated or decompensated cirrhosis but are usually relatively stable. In these patients, some acute event sets off a rapid deterioration of liver function. The cause of this acute episode of decompensation may include toxins, such as alcohol, metabolic abnormalities and infections. The morbidity and mortality of the patient population Conatus plans to study is high, and up to 45 per cent of the patients may die, develop multi-organ failure, or require a liver transplant as a result of the decompensation episode within 28 days of hospitalization. The rapid deterioration in liver function, which may be exacerbated by an altered immune response, leads to life-threatening complications such as renal failure, increased susceptibility to infection, hepatic coma and systemic hemodynamic dysfunction. Liver transplantation is required in some subjects to improve survival and quality of life.
In addition to the phase IIb trial in patients with ACLF, Conatus expects to initiate its planned phase IIb/III clinical trial of emricasan in patients who have developed liver fibrosis post-orthotopic liver transplant due to Hepatitis C virus infection (HCV-POLT) in the second half of 2013.
Conatus is developing its lead compound, emricasan, for the treatment of patients in orphan populations with chronic liver disease and acute exacerbations of chronic liver disease.