REALIZE was a randomized, double-blind, placebo-controlled trial in patients with genotype 1 chronic HCV and compensated liver disease who were previously treated with pegIFN-RBV (N=662). The trial enrolled prior relapsers and prior nonresponders (including partial responders and null responders). Patients received INCIVEK combination treatment for 12 weeks (with and without a 4-week lead-in of pegIFN-RBV alone) followed by treatment with pegIFN-RBV alone for a total of 48 weeks. The control regimen received a telaprevir-matching placebo for the first 16 weeks followed by pegIFN-RBV alone for a total of 48 weeks. The immediate-start and lead-in arms delivered comparable rates of SVR, relapse, and virologic failure; therefore, data were pooled.
INCIVEK was administered at a dosage of 750 mg every 8 hours; the peginterferon alfa-2a dose was 180 µg/week, and the ribavirin dose was 1000 mg/day (patients weighing <75 kg) or 1200 mg/day (patients weighing ≥75 kg). SVR in all trials was defined as HCV RNA <25 IU per mL at last observation within the SVR visit window (i.e., Weeks 32–78 for patients assigned to 24 weeks of treatment and Weeks 56–78 for patients assigned to 48 weeks of treatment).
Eligible patients were/had 1) 18 to 70 years of age, had chronic HCV genotype 1 infection, did not have a sustained virologic response to one previous course of pegIFN-RBV despite receiving at least 80% of the intended dose; 2) had well-characterized data on the previous treatment; 3) detectable HCV RNA; 4) undergone liver biopsy within 18 months before screening; 5) absolute neutrophil count of ≥1200/mm3; and 6) platelet count of ≥90,000/mm3, and a hemoglobin level of ≥12 g/dL in women and ≥13 g/dL in men.1
- Treatment arm 1 (n=266): INCIVEK + pegIFN-RBV for 12 weeks, followed by pegIFN-RBV alone for 36 weeks
- Treatment arm 2 (n=264): pegIFN-RBV for 4 weeks, followed by INCIVEK + pegIFN-RBV for 12 weeks, followed by pegIFN-RBV alone for 32 weeks
- Treatment arm 3 (n=132): pegIFN-RBV alone for 48 weeks
- Patients with HCV RNA >100 IU/mL at Weeks 4, 6, and 8 discontinued INCIVEK
- Patients with HCV RNA <2 log10 decrease from baseline at Week 12 (Week 16 for lead-in arm) discontinued pegIFN-RBV; INCIVEK is complete
- Discontinuation of all treatment if detectable at Week 24 or 36