OPTIMIZE trial: Non-inferiority of twice-daily telaprevir versus administration every 8 hours in treatment-naïve, genotype 1 HCV infected patients
Aims: The ADVANCE study showed that telaprevir (TVR, T) every 8 hours (q8h) combined with peginterferon alfa-2a (P) and ribavirin (R) had superior efficacy to PR alone. Reported here are results from OPTIMIZE, a Phase III, randomized, open-label, international, non-inferiority study comparing twice daily (bid) vs. q8h TVR (NCT01241760).
Methods: Treatment-naive patients with genotype 1 (G1) HCV infection were randomized (stratified by fibrosis stage and IL28B genotype) to 750 mg q8h or 1125 mg bid TVR plus P 180 µg/week and R 1000 or 1200 mg/day for 12 weeks (TVR phase), then PR alone for 12 weeks if Week 4 HCV RNA was < 25 IU/mL target not detected (RVR) or 36 weeks if detectable. The primary endpoint was SVR12 (HCV RNA < 25 IU/mL 12 weeks after the last planned dose of PR). The pre-specified non-inferiority margin was –11%. Secondary objectives included additional efficacy outcomes, safety and tolerability.
Results: 744 patients were randomized and 740 treated. 60% of patients were male, 92% were Caucasian, 15% had bridging fibrosis,14% had compensated cirrhosis, 85% had baseline HCV RNA ≥800,000 IU/mL, 57% had G1a and 29% had IL28B CC. Outcomes were similar between regimens [Table]. TVR bid vs. q8h was non-inferior: difference 1.5% (95% CI: –4.9%, 12.0%). 69% for TVR bid vs. 67% for q8h achieved RVR and were eligible for 24 week treatment duration.
The adverse event (AE) profile was generally similar between arms. The most frequent AEs during the TVR phase were fatigue (47.3%), pruritus (42.7%), anemia (41.6%), nausea (36.5%) and rash (35.3%). AEs leading to discontinuation of TVR included rash (5.3%), anemia (4.6%), pruritus (2.6%), fatigue (1.2%) and maculopapular rash (1.1%). SAEs were reported in 8.5% of patients (TVR phase).
Conclusions: In this study, with a high proportion of patients with bridging fibrosis or compensated cirrhosis, the efficacy of 1125 mg bid TVR was non-inferior to 750 mg q8h offering the potential of simplified dosing to G1 HCV-infected patients. Safety and tolerability were generally similar between regimens and consistent with the known profile of TVR.