| Abstract
| - Introduction. This Phase 3 study evaluated telaprevir (T) in combination with pegylated-IFN alfa-2a (P) and ribavirin (R) in well-characterised G1 prior-PR treatment failure patients including prior PR non-responders (null and partial) and relapsers. Method. REALIZE was a randomised, international, multicentre, double-blind, placebo-controlled trial evaluating efficacy, safety and tolerability of T (750 mg q8 h) plus P (180μg/w) and R (1000-1200 mg/d) compared with PR alone. The treatment arms (randomised 2:2:1, stratified by viral load and prior response) were: 12-weeks T/PR, followed by 36-weeks PR (T12PR48); 4-weeks PR followed by 12 weeks T/PR (T delayed start, DS), then 32-weeks PR (T12(DS)/PR48); 48-weeks PR (Pbo/PR48). The primary objective was efficacy of the T/PR arms in non-responders and relapsers. Secondary objectives included evaluation of T DS and efficacy in prior-null and -partial responders. HCV RNA was quantified using COBAS TaqManÆ v2.0 assay (LLOQ=25 IU/ml). Results. 833 patients were screened, and 662 treated. 70% of patients were male, 93% Caucasian, 26% had cirrhosis, and 89% had baseline HCV RNA ≥800 000 IU/ml. AEs reported more frequently in T arms were rash, pruritus, diarrhoea, anorectal disorders and anaemia. 13% of T/PR patients had premature discontinuation (D/C) of T due to AEs: rash (4%) and anaemia (3%) were the most common AEs leading to T D/C. Conclusion. T/PR SVR was significantly superior to PR in all prior-treatment failure populations including null- and partial-responders. A telaprevir delayed start did not have a significant impact on SVR rates. Safety profile of T/PR was consistent with that observed in treatment naive subjects. Abstract OP03 Table 1 T12/PR48T12 (DS)/PR48Pbo/PR48%RelapsersN=145N=141N=68SVR** (p value*)83 (<0.001)88 (<0.001)24Prior PR Non-respondersN=121N=123N=64SVR** (p value*)41 (<0.001)42 (<0.001)9Partial-respondersN=49N=48N=27SVR** (p value*)59 (<0.001)54 (<0.001)15Prior PR null-responders (<2 log decline in HCV RNA at wk 12 of prior therapy)N=72N=75N=37SVR** (p value*)29 (<0.001)33 (<0.001)5 * In comparison to Pbo/PR48. ** Assessed 24 weeks after planned treatment completion.
|
