http://www.kenes.com/easl2009/Orals/153.htm
Session Title: Parallel Session 1: HEPATITIS C VIRUS DRUG DEVELOPMENT I
Presentation Date: Apr 23, 2009
RESULTS OF A PROOF OF CONCEPT STUDY (C210) OF TELAPREVIR MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAÏVE GENOTYPE 4 HCV PATIENTS
Y. Benhamou1, J. Moussalli1, V. Ratziu2, P. Lebray1, V. Gysen3, K. de Backer3, A. Ghys3, R. van Heeswijk3, T. Vangeneugden3, G. Picchio4, M. Beumont-Mauviel3
1Hôpital Pitié-Salpêtrière, 2Université Pierre et Marie Curie, Paris VI, Paris, France, 3Tibotec BVBA, Mechelen, Belgium, 4Tibotec Inc., Yardley, PA, USA
Background: C210 is an ongoing, partially blinded, randomized, Phase 2a study of telaprevir (TVR), administered as monotherapy and in combination with peginterferon alfa 2a (Peg-IFN) and ribavirin (RBV), investigating early viral kinetics of HCV-RNA decay in treatment-naïve subjects with genotype 4 infection. We report results of the primary analysis conducted at day 15 of treatment.
Methods: HCV genotype 4 subjects were randomized to receive
TVR 750mg q8h alone (arm A; n=8),
TVR with Peg-IFN 180µg/week and RBV 1000-1200mg/day (arm B; n=8),
or Peg-IFN and RBV plus placebo (arm C; n=8) for 15 days.
Viral load was measured using Taqman assay (limit of detection 1-log increase in HCV-RNA above nadir or >100 IU/mL HCV-RNA after previously undetectable HCV-RNA. An ITT analysis was performed when all treated subjects had completed 15 days of dosing or had discontinued earlier.
Results: 38% of enrolled patients were Egyptian and 25% were Caucasian; none had cirrhosis and 58% had HCV-RNA >800,000 IU/mL. Genotype 4a was the most prevalent subtype (50%).
The mean (SE) log10 changes in HCV-RNA at days 3/15 were -1.2(0.28)/-0.9(0.46), -2.1(0.29)/-3.4(0.65), and -1.0(0.26)/-2.0(0.40), while the mean (SE) log10 maximum HCV-RNA change was -1.4(0.30), -3.5(0.48) and -2.0(0.40) for arms A, B and C, respectively.
By day 15, 0%, 13%, and 0% of subjects had undetectable (< 10 IU/mL) HCV-RNA in arms A, B and C, respectively; vBT during the dosing period was observed in 5, 1 and 0 patients, respectively. The overall incidence of adverse events (AEs) was similar across arms and in line with previous reports. One patient in arm A had a serious AE that was considered unrelated to TVR but led to treatment discontinuation.
Conclusions: TVR in combination with Peg-IFN and RBV had greater activity against HCV genotype 4 than Peg-IFN and RBV alone or TVR monotherapy. The potential role of TVR in combination with Peg-IFN and RBV in the treatment of HCV genotype 4-infected patients remains under investigation.
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(I think I'll try to decipher the above results-Willy)
Arm A Day 3 -1.2 log Day 15 -0.9 log drop % UND- 0% Max log delta -1.4
(TVR monotherapy)
Arm b Day 3 -2.1 Day 15 -3.4 % Und- 13% Max log delta -3.5
(TVR TID plus SOC)
Arm c Day 3 -1.0 Day 15 -2.0 % UND- 0% Max log delta -2.0
(tvr PLACEBO plus SOC)
Jim or anyone; at some point we will see this on a nice graph or chart but in the meanwhile this is how I decipher the results. I believe that the genotype 2 and 3 results may follow this pattern but of course it is even more jumbled since there are 2 different genotypes. Better charts will follow I'm sure. (by the way delta = change)
Willy