Treatment with telaprevir-based therapy after exposure to PEG-IFN/RBV in the realize study: Results from the phase IIIB C219 rollover study.

Background and Aims: C219 (NCT01054573) was an open-label, single-arm, rollover study that examined telaprevir (TVR)-based therapy in patients with chronic HCV genotype 1 infection who failed to achieve a sustained virologic response (SVR) following peginterferon/ribavirin (PR) alone in the REALIZE study, or with >=1 dose of TVR in Phase I studies. We present data from patients previously treated with PR alone in the REALIZE study. Method(s): Patients received TVR 750mg q8h plus PR at standard doses (180 mg once-weekly and 1000 or 1200 mg/day, respectively) for 12 weeks, followed by PR alone for 36 weeks. HCVRNA levels were evaluated using the COBAS TaqMan assay v2.0. The primary endpoint was SVR24, defined as having HCVRNA '<25 IU/mL, target not detected' 24 weeks after last medication intake. (Table presented) Results: Of the 81 patients who did not achieve SVR in the PR arm of the REALIZE study, 27 (33%) were relapsers, 22 (27%) partial responders, and 32 (40%) null responders. The study included 70% males, mostly Caucasian (93%) and median age 53 years. At baseline, an equal proportion of patients had genotype 1a/1b (50%/50%); 25% had cirrhosis. Median log10 HCVRNA was 6.62 IU/mL, with HCVRNA >=800,000 IU/mL in 83% of cases. 90% of patients completed TVR treatment, and 67% completed PR treatment. Overall, 81%, 73%, and 34% of prior relapsers, partial responders and null responders, respectively, achieved SVR (Table). Among patients with virologic failure, observed resistant variants were consistent with those previously described for TVR. The most frequent (>=30%) adverse events (AEs) occurring during TVR treatment phase were pruritus (42%), fatigue (41%), rash (36%), and anemia (32%), most of which were Grade 1/2. Serious AEs occurred in 5 (6%) patients in the TVR phase: anemia (4%), biliary colic and pyelonephritis (each 1%). TVR was permanently discontinued in 4 (5%) patients due to AEs. Conclusion(s): In this treatment-experienced population, the efficacy, s