og10 by Week 12, but never achieved SVR [partial responders] or undetectable HCV-RNA at end of prior treatment with a subsequent detectable HCV-RNA in plasma [relapsers]). Subjects with less than 2-log10 decrease in HCV-RNA by week 12 of previous treatment (prior null responders) were not eligible for enrollment in this trial. Subjects were randomized in a 1:2:2 ratio and stratified based on response to their previous qualifying regimen (relapsers vs. partial responders) and by HCV subtype (1a vs. 1b) to one of the following treatment arms:
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PegIntron + REBETOL for 48 weeks (PR48)
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PegIntron + REBETOL for 4 weeks followed by VICTRELIS 800 mg three times daily + PegIntron + REBETOL for 32 weeks. The subjects were then continued on different treatment regimens based on TW8 and TW12 response-guided therapy (VICTRELIS-RGT). All subjects in this treatment arm were limited to 32 weeks of VICTRELIS.
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Subjects with undetectable HCV-RNA at TW 8 (early responders) and TW 12 completed therapy at TW36 visit.
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Subjects with a detectable HCV-RNA at TW 8 but subsequently undetectable at TW 12 (late responders) were changed in a blinded fashion to placebo at the TW 36 visit and continued treatment with PegIntron + REBETOL for an additional 12 weeks, for a total treatment duration of 48 weeks.
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PegIntron + REBETOL for 4 weeks followed by VICTRELIS 800 mg three times daily + PegIntron + REBETOL for 44 weeks (VICTRELIS-PR48).
All subjects with detectable HCV-RNA in plasma at TW 12 were discontinued from treatment. Sustained Virologic Response (SVR) was defined as plasma HCV-RNA undetectable at Follow-up Week 24. Plasma HCV-RNA results at Follow-up Week 12 were used if plasma HCV-RNA results at Follow-up Week 24 were missing.
Mean age of subjects randomized was 53 years. The racial distribution of subjects was as follows: 85% White, 12% Black, and 3% others. The distribution of subjects by gender was 67% men and 33% women.
The addition of VICTRELIS to the PegIntron and REBETOL therapy significantly increased the SVR rates compared to PegIntron/REBETOL alone (59% to 66% VICTRELIS-containing arms vs. 23% PR48 control) for randomized subjects who received at least one dose of any study medication (Full-Analysis-Set population) (see Table 12).
Table 12 Sustained Virologic Response (SVR)*, † and Relapse‡ Rates for Subjects Who have Failed Previous Therapy with Peginterferon Alfa and Ribavirin
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VICTRELIS-RGT |
VICTRELIS-PR48 |
PR48 |
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Previous Partial Responder = subject who failed to achieve SVR after at least 12 weeks of previous treatment with peginterferon alfa and ribavirin, but demonstrated a ≥2-log10 reduction in HCV-RNA by Week 12. |
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Previous Relapser = subject who failed to achieve SVR after at least 12 weeks of previous treatment with peginterferon alfa and ribavirin, but had undetectable HCV-RNA at the end of treatment. |
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