Below is corrected Abstract 1385. The original Abstract 1385 appeared in Volume 48, Number 4 (Supplement), October 2008.
Phase 2 Study of Telaprevir Administered q8h or q12h with Peginterferon-Alfa-2a or -Alfa-2b and Ribavirin in Treatment-Naïve Subjects with Genotype 1 Hepatitis C: Week 4 Interim Results
X. Forns1; P. Marcellin2; T. Goeser3; P. Ferenci4; F. Nevens5; G. Carosi6; J. P. Drenth7; K. De Backer8; R. van Heeswijk8; T. J. Vangeneugden8; G. Picchio9; M. Beumont-Mauviel8;
1. Liver Unit, University of Barcelona, Barcelona, Spain.
2. Hôpital Beaujon, Clichy, France.
3. Klinikum der Universität zu Köln, Köln, Germany.
4. Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria.
5. Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium.
6. Clinic of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
7. Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
8. Tibotec BVBA, Mechelen, Belgium.
9. Tibotec Inc., Yardley, PA, USA.
Background: Study C208 is an ongoing open-label, randomized Phase 2 study of telaprevir (TVR) administered q8h or q12h in combination with peginterferon-alfa-2a (Peg-IFN-alfa-2a) or Peg-IFN-alfa-2b and ribavirin (T/PR) in treatment-naïve subjects with HCV genotype 1 infection. We report the results of an interim analysis conducted at week 4 of treatment.
Methods: 161 subjects were randomized into 4 arms (table). Subjects in all arms received T/PR treatment for 12 weeks, and will subsequently receive either 12 or 36 additional weeks of PR based on rapid virologic response (RVR) criterion. Subjects who met the definition of viral breakthrough (≥1-log increase in HCV RNA above nadir) discontinued TVR dosing and will complete 48 weeks of PR. An intent-to-treat analysis was performed when all treated subjects had completed week 4 of treatment or had discontinued earlier than week 4. The analysis also assessed all treatment or TVR dosing discontinuations including subjects who discontinued beyond week 4, up to the time of data cutoff. The proportion of subjects with HCV RNA below the limit of detection (TaqMan assay LOD 10 IU/mL) at week 4 (RVR) is reported.
Results: Baseline characteristics were balanced across arms. Although differences did not reach statistical significance, a higher rate of HCV RNA clearance was observed at week 4 in arms A and C compared with arms B and D. The proportion of subjects with undetectable HCV RNA at week 4 was 82% and 85% for arms A and C, respectively; and 71% and 68% for arms B and D, respectively. Up to week 4, the number of subjects with viral breakthrough was 0 and 2 in arms A and C, respectively; and 2 and 1 in arms B and D, respectively. The overall proportion of TVR discontinuations for any reason was 12% (n=19). Similar discontinuation rates were observed in each of the arms.
Conclusions: In the context of the two currently available standard-of-care regimens, TVR 750 mg q8h or 1125 mg q12h in combination with PR yielded high rates of virological response and low viral breakthrough at week 4. Differences in the proportion of subjects with undetectable HCV RNA were observed between arms receiving different PR regimens. Future results from a week 12 interim analysis will further assess the therapeutic potential of TVR q12h dosing, as well as potential differences in efficacy related to the combination of TVR with either Peg-IFN-alfa-2a or Peg-IFN-alfa-2b and ribavirin.