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Prove2 Study: Treatment of Chronic Hepatitis C with Telaprevir (TVR)in Combination with Peginterferon-Alfa-2a with or Without Ribavirin, Interim Analysis Results Christophe Hezode1, Peter Ferenci2, Geoffrey M Dusheiko3, Albert Tran4, Jean-Didier Grange5, Philippe Mathurin6, Wolfgang E Schmidt7, Helmut Diepolder8, Patrick Marcellin9, Heiner Wedemeyer10, Nicole Forestier11, Wendy Mangels12, Shahin Gharakhanian12, Robert S Kauffman12, John Alam12, Jean-Michel Pawlotsky1, Stefan Zeuzem11
1. AP-HP Henri Mondor Hospital, University Paris 12, Creteil, France, 2. Medical University of Vienna, Vienna, Austria, 3. Royal Free Hospital, London, United Kingdom, 4. University Hospital (CHU),University of Nice, Nice, France, 5. AP-HP Tenon Hospital, Paris, France, 6. University Hospital (CHU), University of Lille, Lille, France, 7. St Josef Hospital, University of Bochum, Bochum, Germany, 8. LMU, Munich, Germany, 9. AP HP Beaujon Hospital, Clichy, France, 10. Hannover Medical School, Hannover, Germany, 11. J.W. Goethe University Hospital, Frankfurt, Germany, 12. Medicinal Development Group, Vertex Pharmaceuticals, Inc., Cambridge, MA, USA
Background: Telaprevir is an inhibitor of NS3.4A protease that demonstrates rapid and consistent reductions of HCV RNA. PROVE2 is a phase 2 assessment of safety, efficacy and shorter durations in chronic genotype 1 HCV treatment-naïve patients without cirrhosis. Methods: 323 patients were randomized in 4 arms. Control arm received current treatment Peg-IFN (P) 180 mcg/weekly + Ribavirin (R) 1000-1200 mg, TVR-placebo for 48 weeks. 24-w arm: TVR 750 mg q8h with P/R for 12-w, followed by P/R for a further 12 weeks. 12-w arm: TVR 750 q8h with P+R for 12 weeks. No R arm: TVR/P for 12 weeks. Plasma HCV RNA was quantified by the Roche Taqman™ assay (LOD 10 IU/mL). Results: Patients had a median weight of 71kg (45-115), 59% were male, 94% were Caucasian, 7.5 % had stage F3 fibrosis. Median baseline HCV RNA was 6.4 Log10IU/ml (3.3-7.7) and 83% of patients had HCV RNA >800,000 IU/mL. 10% of patients within the TVR/P±R arms discontinued due to AEs in the first 12-weeks. Pruritus, nausea, rash and anemia were the most common AEs with an incidence of ≥ 10% in the TVR arms versus controls. Rash was classified as grade III in 6% and the other AEs were grade III in ≤ 2% of patients. In those patients experiencing rash, 7% discontinued in the 12 and 24-week arms, 3% in the no R arm, none in control arm. Table summarizes ITT viral outcomes at week 4 and 12 with 12-week follow up for the 24-week arm and 24-week follow up results for 12-week/No R arms. Total relapse rates, in patients completing 12-week and 24-weeks, were 28% and 14%, respectively, but lower with 22% and 11%, respectively, in those with Rapid Viral Response RVR. Conclusion: Telaprevir combined with Pegylated-interferon and ribavirin produced a significantly greater anti-viral effect compared to Pegylated-interferon and ribavirin alone in patients with chronic genotype 1 HCV within a shorter treatment duration. Telaprevir and Pegylated-interferon had lower antiviral activity than the triple combination of telaprevir, Pegylated-interferon and ribavirin. Skin events, and anemia were more common and rash more severe in the TVR/PR arms. PROVE2 supports the use of Rapid Viral Response (RVR) for clinical monitoring and management.