Telaprevir in Combination with Peginterferon Alfa2a and Ribavirin for 24 or 48 weeks in Treatment-Naïve Genotype 1 HCV Patients who Achieved an Extended Rapid Viral Response: Final Results of Phase 3 ILLUMINATE Study
K. E. Sherman; S. L. Flamm; N. H. Afdhal; D. R. Nelson; M. S. Sulkowski; G. T. Everson; M. W. Fried; K. Kleber; M. Martin; A. J. Sankoh; R. S. Kauffman; S. George; C. I. Wright; F. Poordad
Background: The Phase 3 open-label study, ILLUMINATE, evaluated patients randomized to two durations of therapy among those who achieved extended rapid viral response (eRVR).
Methods: HCV genotype 1 treatment-naïve patients (pts) were treated with telaprevir (T; 12 weeks (wk), 750 mg po q8h) with peginterferon alfa2a (P; 180 μg/week) and ribavirin (R; 1000-1200 mg/day). Pts who achieved eRVR (undetectable HCV RNA at Wks 4 and 12) were randomized at Wk 20 to continue receiving PR for 24 or 48 wks of total treatment. Pts not achieving eRVR were assigned 48 wks of treatment. Pts who failed to achieve a 2log10 drop at 12 wks or had detectable HCV RNA by 24 wks were discontinued as virologic failures. The primary endpoint was the proportion of randomized pts achieving SVR 24 wks after planned treatment completion. The study was powered to rule out non-inferiority (NI) of 24-wk to 48-wk treatment among randomized pts with an NI of -10.5%. Analyses were based on the intent-to-treat (ITT) randomized population.
Results: 540 pts were treated at 74 sites: 60.2% male, 79.1% Caucasian, 13.5% Black, median HCV RNA log10 6.5 IU/ml, 11.3% cirrhosis. Efficacy: 72% (n=389) of pts achieved RVR; 65.2% (n=352) of pts achieved eRVR. 322 (59.6%) pts were randomized (1:1) to either a 24-wk or 48-wk arm. SVR was 92% among pts randomized to 24 wks (n=162). SVR was 87.5% (Δ4.5%, 2-sided 95% C.I. = -2.1% to +11.1%) among pts randomized to 48 wks (n=160). Overall, SVR was 71.9% (ITT analysis). 36 pts (6.7%) discontinued treatment due to virologic failure. Safety: 94 pts (17.4%) had permanent discontinuation of all study drugs (D/C) for AEs. Fatigue (n=22) and anemia (n=12) were the most common AEs leading to D/C. AEs led to treatment D/C after Wk 20 in 1 (0.6%) and 20 (12.5%) of eRVR+ pts randomized to 24 wks and 48 wks of treatment, respectively. Treatment D/C due to anemia and rash were 3 (0.6%) and 6 (1.1%) pts, respectively, during the telaprevir treatment phase.
Conclusions: Among patients who achieved eRVR, a 24-week telaprevir-based regimen was non-inferior to 48-week telaprevir-based regimen (92% SVR compared to 87.5%). Response-guided treatment led to 71.9% SVR overall and nearly two-thirds of the patients were eligible for shorter duration of treatment. Permanent discontinuation of all study drugs due to adverse events occurred in 17.4% of patients. Among eRVR randomized patients, there were more adverse events and adverse event-related treatment discontinuations in the 48-week versus 24-week arm. These results support response-guided therapy for telaprevir-based regimens in treatment-naïve patients.