cts were randomized in a 1:1:1 ratio within two separate cohorts (Cohort 1/non-Black and Cohort 2/Black) and were stratified by HCV genotype (1a or 1b) and by HCV-RNA viral load (≤400,000 IU/mL vs. >400,000 IU/mL) to one of the following three treatment arms:
•PegIntron + REBETOL for 48 weeks (PR48).
•PegIntron + REBETOL for four weeks followed by VICTRELIS 800 mg three times daily + PegIntron + REBETOL for 24 weeks. The subjects were then continued on different regimens based on Treatment Week (TW) 8 through TW 24 response-guided therapy (VICTRELIS-RGT). All subjects in this treatment arm were limited to 24 weeks of therapy with VICTRELIS.
•Subjects with undetectable HCV-RNA at TW 8 (early responders) and who were also negative through TW24 discontinued therapy and entered follow-up at the TW 28 visit.
•Subjects with detectable HCV-RNA at TW 8 or any subsequent treatment week but subsequently negative at TW 24 (late responders) were changed in a blinded fashion to placebo at the TW 28 visit and continued therapy with PegIntron + REBETOL for an additional 20 weeks, for a total treatment duration of 48 weeks.
•PegIntron + REBETOL for four 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 TW24 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 49 years. The racial distribution of subjects was as follows: 82% White, 14% Black, and 4% others. The distribution of subjects by gender was 60% men and 40% women.
The addition of VICTRELIS to PegIntron and REBETOL significantly increased the SVR rates compared to PegIntron and REBETOL alone in the combined cohort (63% to 66% VICTRELIS-containing arms vs. 38% PR48 control) for randomized subjects who received at least one dose of any study medication (Full-Analysis-Set population). SVR rates for Blacks in a predefined analysis who received the combination of VICTRELIS with PegIntron and REBETOL were 42% to 53% (see Table 10).
Table 10 Sustained Virologic Response (SVR)* , † and Relapse Rates‡ for Previously Untreated Subjects Study Cohorts VICTRELIS-RGT VICTRELIS-PR48 PR48
Cohort 1 Plus Cohort 2 (all subjects) n=368 n=366 n=363
SVR† % 63 66 38
Relapse‡ % 9 9 22
(n/N) (24/257) (24/265) (39/176)
Cohort 1 Plus Cohort 2 (subjects without cirrhosis)
SVR† , § % 65 68 38
(n/N) (228/352) (232/342) (132/350)
Cohort 1 (non-Black) n=316 n=311 n=311
SVR† % 67 68 40
Relapse‡ % 9 8 23
(n/N) (21/232) (18/230) (37/162)
Cohort 2 (Black) n=52 n=55 n=52
SVR† % 42 53 23
Relapse‡ % 12 17 14
(n/N) (3/25) (6/35) (2/14)
*The Full Analysis Set (FAS) consisted of all randomized subjects (N=1097) who received at least one dose of any study medication (PegIntron, REBETOL, or VICTRELIS).
†Sustained Virologic Response (SVR): reported as plasma HCV-RNA < 25 IU/mL at follow-up week (FW) 24. The last available HCV-RNA value in the period at or after FW24 was used. If HCV-RNA value at FW24 was missing, the FW12 value was carried forward.
‡Relapse rate was the proportion of sub |
