• DOI:10.3851/IMP1894
• Corpus ID: 12900406

Rapid Viral Response of Once-Daily Tmc435 plus Pegylated Interferon/Ribavirin in Hepatitis C Genotype-1 Patients: A Randomized Trial

@article{Manns2011RapidVR,
  title={Rapid Viral Response of Once-Daily Tmc435 plus Pegylated Interferon/Ribavirin in Hepatitis C Genotype-1 Patients: A Randomized Trial},
  author={Michael P. Manns and Hendrik W Reesink and Thomas Berg and Geoffrey Dusheiko and Robert Flisiak and Patrick Marcellin and Christophe Moreno and Oliver Lenz and Paul Meyvisch and Monika P Peeters and Vanitha J. Sekar and Kenneth Alan Simmen and Ren{\'e} Verloes},
  journal={Antiviral Therapy},
  year={2011},
  volume={16},
  pages={1021 - 1033}
}

• M. Manns, H. Reesink, +10 authors R. Verloes
• Published 1 October 2011
• Medicine
• Antiviral Therapy

Background Antiviral activity of TMC435, an oral, once-daily, HCV NS3/4A protease inhibitor, was evaluated with pegylated interferon-α2a/ribavirin (P/R) in HCV genotype-1 patients. Methods Optimal Protease inhibitor Enhancement of Response to TherApy (OPERA-1; TMC435-C201; NCT00561353) is a Phase IIa, randomized, placebo-controlled study. Treatment-naive patients (n=74) received 25, 75 or 200 mg TMC435 once daily, or placebo for 7 days followed by 21 days of triple therapy with P/R, or triple therapy for 28 days. Treatment-experienced patients (n=37; 56.8% with cirrhosis) received 75, 150 or 200 mg TMC435 once daily, or placebo with P/R for 28 days. Patients continued P/R up to week 48. Results Treatment-naive patients who received initial monotherapy had a rapid decline in HCV RNA by day 3. At day 7, HCV RNA reductions were greatest for the 75 and 200 mg doses (0.02, -2.63, -3.43 and -4.13 log10 IU/ml for placebo, and TMC435 25, 75 and 200 mg, respectively). At day 28, all patients who received triple therapy with TMC435 75 or 200 mg had HCV RNA<25 IU/ml versus 4/9 for placebo. In total, 18/28 treatment- experienced patients (9/9 prior relapsers, 9/19 non-responders) who received TMC435 had HCV RNA<25 IU/ml at day 28 versus 0/9 for placebo; similar results were observed for the 150 and 200 mg doses. Most adverse events were grade 1/2. No relevant changes in laboratory parameters occurred, except mild and reversible bilirubin elevations, mostly at the 200 mg dose. Conclusions Once-daily TMC435 with P/R showed potent, dose-dependent antiviral activity over 28 days, and had a favourable tolerability profile.