Treatment with Telaprevir/PEG-IFN/RBV after 14-day Telaprevir exposure in phase I studies: 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 infected with chronic genotype 1 HCV who failed to achieve a sustained virologic response (SVR) following peginterferon/ribavirin (PR) alone in the REALIZE study, or with ≥1 dose of TVR (alone or in combination with PR) in Phase I studies (101 and 103). Here we present the primary endpoint, SVR24actual, for patients who had prior exposure to TVR only from the Phase I studies.

Methods: In studies 101/103, all patients received 14 days TVR monotherapy. TVR-resistant variants had been detected by clonal sequence analysis after dosing in studies 101/103 for all patients. In the C219 study, patients received TVR 750 mg q8h plus PR at standard doses (180 µg once-weekly and 1000 or 1200 mg/day, respectively) for 12 weeks, followed by 36 weeks of PR. HCV RNA levels were determined using COBAS TaqMan assay v2.0. SVR24actual was defined as HCV RNA '< 25 IU/mL target not detected' at least 24 weeks after the last medication intake.

Results: Nine patients from trial 101 (n = 8) or 103 (n = 1): six subtype 1a; three subtype 1b, were enrolled. Baseline HCV RNA was ≥800,000 IU/mL for all patients; four patients had cirrhosis. Median time since last TVR exposure was 5.7 years (range 4.9 – 6.0). No TVR-resistant variants were detected by population sequencing or deep sequencing (Illumina assay) before entering study C219. Five patients achieved SVR (Table); two patients had on-treatment virologic failure; two patients relapsed. In three non-SVR patients with available sequence data at the time of failure, the most common known TVR-resistant variants V36 M + R155K were detected, similar to those found in the 101/103 studies. Observed adverse events were consistent with those reported for Phase III studies.

Conclusions: Among patients who had previously received 14 days of TVR monotherapy, 5/9 achieved SVR with TVR/PR. For treatment failures, ongoing deep sequencing analysis will further explore a possible phylogenetic relationship of isolates harbouring resistant variants observed during first and second TVR exposure.