Source Department of Gastroenterology and Hepatopancreatology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
BACKGROUND & AIMS: TMC435 is an investigational, once-daily, oral NS3/4A protease inhibitor currently in phase III development for the treatment of hepatitis C virus (HCV) infection. Phase I and II studies in patients infected with HCV genotype 1 have demonstrated that TMC435 is generally well tolerated, has a pharmacokinetic profile that supports once daily dosing, and demonstrates potent antiviral activity. This phase IIa study (TMC435-C202; NCT00812331) was conducted to investigate the antiviral activity, safety, tolerability, and pharmacokinetics of TMC435 in treatment-naїve patients infected with HCV genotypes 2 to 6.
METHODS: The study consisted of 7 days of monotherapy with TMC435 (200 mg once daily). Patients could begin treatment with pegylated interferon/ribavirin from Day 8 with a follow-up period up to Days 37-42.
RESULTS: Thirty-seven patients were enrolled in Germany, Belgium and Thailand. For the primary endpoint at Day 8, the mean (±standard error) change in plasma HCV ribonucleic acid (log(10) IU/mL) from baseline was greatest for genotypes 6 (-4.35±0.29) and 4 (-3.52±0.43), followed by genotypes 2 (-2.73±0.71) and 5 (-2.19±0.39). No antiviral activity was evident for genotype 3. Viral breakthrough occurred in six patients during the monotherapy phase and in six additional patients during PegIFN/RBV-only period. All adverse events were mild or moderate and there were no discontinuations during the TMC435 monotherapy period.
CONCLUSIONS: The results of this phase IIa proof-of-concept trial provide evidence that TMC435 has a spectrum of activity against multiple HCV genotypes, except for genotype 3. In this study, TMC435 was generally safe and well tolerated.