| Abstract
| - Aim. The ADVANCE study is a 3-arm double-blind, randomised, placebo-controlled Phase 3 study assessing efficacy and safety of two telaprevir (TVR, T)-based response-guided regimens compared with peginterferon alfa-2a 180 _g/week and ribavirin 1000-1200 mg/day (PR) in treatment-naive patients with chronic genotype 1 HCV infection. Method. Treatment arms were (a) T 750 mg q8 h in combination with PR for 8 weeks, followed by additional weeks of PR; (b) T 750 mg q8 h in combination with PR for 12 weeks, followed by additional weeks of PR; (c) PR for 48 weeks (control arm). Patients in T arms achieving an extended rapid viral response (eRVR, undetectable HCV RNA at weeks 4 and 12) received a total of 24 weeks of therapy while those who did not received a total of 48 weeks of therapy. Randomisation was 1:1:1 and patients were stratified by HCV RNA (<800 000 IU/ml, ≥800 000 IU/ml), and genotype 1a vs. 1b. The primary endpoint was SVR (undetectable HCV RNA 24 weeks after last planned dose of treatment). The primary analysis was based on the Full Analysis (intention-to-treat) dataset. Safety is presented for TVR/Placebo duration phase. Results. Of 1088 patients, 839 (77%) had HCV RNA ≥800 000 IU/ml, 631 (58%) were genotype 1a, 636 (58%) male, 94 (9%) black, 117 (11%) Latino/Hispanic, 231 (21%) had bridging fibrosis or compensated cirrhosis. The most common (>25%) AEs in the T arms were fatigue, pruritus, nausea, headache, anaemia, rash, influenza-like illness, insomnia, fever, and diarrhoea. Discontinuation of treatment due to AEs occurred in 8% in T8PR, 7% in T12PR and 4% in PR48; due to rash occurred in 0.5%, 1.4% and 0.0% and due to anaemia occurred in 3.3%, 0.8% and 0.6% in T8PR, T12PR and control arms, respectively. Conclusion. A significantly greater proportion of patients achieved SVR with 12-week and 8-week telaprevir-based combination regimens (75% and 69%, respectively), compared with PR48 control arm (44%, p<0.0001). The safety and tolerability profile of telaprevir in the ADVANCE trial was consistent with the profile previously reported, with an improvement in treatment discontinuation rates due to adverse events, including rash and anaemia. These first Phase 3 results confirm the clinical benefit previously reported in Phase 2. Abstract P70 Table 1 Viral responseT8PR N=364T12PR N=363PR48 N=361Patients achieving RVR, n (%)242 (66)246 (68)34 (9)Patients with HCV RNA undetectable at end of treatment (EOT), n (%)295 (81)314 (87)229 (63)Patients achieving SVR, n (%)250 (69)*271 (75)*158 (44)Difference in SVR rates, TVR arms vs control, % (95% CI)25 (18 to 32)31 (24 to 38)NAPatients with relapse, n (%)28 (9)27 (9)64 (28) * p<0.0001, Denominator is number of patients with HCV RNA undetectable at EOT.
|
