The Phase 3 results from the ADVANCE study confirm the clinical benefits of telaprevir-based combination therapy regimens. The study reports an improvement in treatment discontinuation rates due to adverse events compared to Phase 2 studies, and demonstrates an increase in sustained viral response (SVR) in patients with hepatitis C virus (HCV). The primary endpoint for this study was SVR 24 weeks after last treatment.
The study was conducted on 1088 treatment-naive HCV patients, all of whom had genotype 1. For the three arms of the trial, one group of patients was treated with 750 mg of telaprevir every eight hours in combination with peginterferon alfa-2a 180 ug/week and ribavirin 1000-1200 mg/day for 12 weeks, while the second group was given the same treatment but for only 8 weeks. Patients in the first group (T12PR) were treated for an additional 12 weeks of peginterferon and ribavirin if HCV RNA was undetectable at weeks 4 and 12, for a total of 24 weeks of treatment, and an additional 36 weeks if HCV RNA was detectable at week 4 or week 12, for a total of 48 weeks' treatment. Patients in the second group (T8PR) were treated with peginterferon and ribavirin for an additional 16 weeks if HCV RNA was undetectable at weeks 4 and 12, and for an additional 40 weeks if HCV RNA was detectable at either week 4 or 12, for a total of 24 or 48 weeks of treatment, respectively. Patients in the control group were treated with peginterferon alfa-2a and ribavirin for 48 weeks.
SVR was 75 percent for those receiving telaprevir combination treatment for 12 weeks, 69 percent for those receiving telaprevir combination treatment for 8 weeks, and 44 percent for those receiving standard of care. Extended rapid virologic response (HCV RNA undetectable at weeks 4 and 12) was attained in 58 percent, 57 percent, and 8 percent, respectively. During the telaprevir/placebo treatment phase, adverse events leading to treatment discontinuation occurred in 7 percent of patients in the arm receiving telaprevir combination treatment for 12 weeks, 8 percent in telaprevir for 8 weeks, and 4 percent in the peginterferon alfa-2a and ribavirin arm.
American Association for the Study of Liver Diseases (AASLD)