Janssen R&D Ireland (Janssen) has started two Phase III trials to evaluate the efficacy and safety of the NS3/4A protease inhibitor simeprevir in combination with the nucleotide inhibitor sofosbuvir to treat chronic genotype 1 hepatitis C virus (HCV) infection in treatment-naive and treatment-experienced patients with and without cirrhosis.
The first trial, known as OPTIMIST-1 (Optimal Treatment with a simeprevir and sofosbuvir Therapy), is a Phase III, multicentre, open-label, randomised study investigating the efficacy and safety of simeprevir 150mg in combination with sofosbuvir 400mg.
In the OPTIMIST-1 trial, the combination drug will be given once daily for eight or 12 weeks in chronic HCV genotype 1 infected patients without cirrhosis who are HCV treatment naive or treatment experienced.
The second multicentre, open-label, single-arm Phase III trial called OPTIMIST-2 will also evaluate the efficacy and safety of simeprevir 150mg in combination with sofosbuvir 400 mg.
The combination will be given once daily for 12 weeks in HCV genotype 1 infected patients with cirrhosis who are HCV treatment naive or treatment experienced.
The company said that ribavirin will not be administered in the OPTIMIST trials, which is expected to enrol about 400 patients in the US and Canada.
Primary efficacy endpoint in each trial is the proportion of patients achieving sustained virologic response 12 weeks after the end of treatment (SVR12).
In the US, Canada, Japan and Russia, simeprevir is approved for the treatment of genotype 1 HCV as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin.
The European Medicines Agency (EMA’s) Committee for Medicinal Products for Human Use (CHMP) has earlier adopted a positive opinion, recommending marketing authorisation in the EU for the use of simeprevir in combination with other medicinal products for the treatment of chronic HCV.
The combination of simeprevir and sofosbuvir was previously assessed in the Phase II COSMOS trial.
Janssen Hepatitis Disease area leader Gaston Picchio said the combination of simeprevir and sofosbuvir with and without ribavirin showed efficacy and safety in treatment-naive and treatment-experienced patients, including those with cirrhosis, in the Phase II COSMOS study.
"The initiation of these Phase III clinical trials is the latest fulfillment of Janssen’s commitment to investigate the utility of simeprevir for patients with chronic hepatitis C infection," Picchio said.
Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir.
It is indicated for the treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 infected patients with compensated liver disease, including cirrhosis.
Image: Hepatitis C is a blood-borne infectious disease of the liver. Photo: courtesy of freedigitalphotos.net.