re comparable to placebo.
14 CLINICAL STUDIES
14.1 Description of Adult Clinical Studies
The efficacy and safety of INCIVEK in subjects with genotype 1 chronic hepatitis C were eva luated in three adequate and well-controlled clinical trials: two in treatment-naïve subjects and one in previously treated subjects (relapsers, partial responders, and null responders). Subjects in these studies had compensated liver disease, detectable HCV-RNA, and liver histopathology consistent with chronic hepatitis C. In all three studies, INCIVEK was administered at a dosage of 750 mg every 8 hours; the peginterferon alfa-2a (Peg-IFN-alfa-2a) dose was 180 µg/week, and the ribavirin (RBV) dose was 1000 mg/day (subjects weighing less than 75 kg) or 1200 mg/day (subjects weighing greater than or equal to 75 kg). Plasma HCV-RNA values were measured during the clinical trials using the COBAS® TaqMan® HCV test (version 2.0), for use with the High Pure System. The assay had a lower limit of quantitation of 25 IU/mL. SVR in all studies was defined as HCV-RNA less than 25 IU/mL at 24 weeks after the planned end of treatment.
14.2 Treatment-Naïve Adults
Study 108 (ADVANCE)
Study 108 was a randomized, double-blind, parallel-group, placebo-controlled, trial conducted in treatment-naïve subjects (had received no prior therapy for HCV, including interferon or pegylated interferon monotherapy). INCIVEK was given for the first 8 weeks of treatment (T8/PR regimen) or the first 12 weeks of treatment (T12/PR regimen) in combination with Peg-IFN-alfa-2a/RBV for either 24 or 48 weeks. Subjects who had undetectable HCV-RNA at weeks 4 and 12 (extended Rapid Virologic Response [eRVR]) received 24 weeks of Peg-IFN-alfa-2a/RBV treatment, and subjects who did not have undetectable HCV-RNA at weeks 4 and 12 (no eRVR) received 48 weeks of Peg-IFN-alfa-2a/RBV treatment. The control regimen (Pbo/PR48) had a fixed treatment duration, with telaprevir-matching placebo for the first 12 weeks and Peg-IFN-alfa-2a/RBV for 48 weeks.
The 1088 enrolled subjects had a median age of 49 years (range: 18 to 69); 59% of the subjects were male; 23% had a body mass index greater than or equal to 30 kg/m2; 9% were Black; 11% were Hispanic or Latino; 77% had baseline HCV-RNA levels greater than 800,000 IU/mL; 15% had bridging fibrosis; 6% had cirrhosis; 59% had HCV genotype 1a; and 40% had HCV genotype 1b.
Table 10 shows the response rates for the T12/PR and Pbo/PR48 groups.
Table 10: Response Rates: Study 108 Treatment Outcome T12/PR
N = 363
n/N (%) Pbo/PR48
N = 361
n/N (%)
Overall SVR 79% (285/363) 46% (166/361)
eRVR 58% (212/363) 8% (29/361)
SVR in eRVR subjects 92% (195/212) 93% (27/29)
No eRVR 42% (151/363) 92% (332/361)
SVR in no eRVR subjects 60% (90/151) 42% (139/332)
Outcome for Subjects without SVR
On-treatment virologic failure* 7% (26/363) 29% (105/361)
Relapse† 4% (11/298) 24% (53/220)
Other‡ 11% (41/363) 10% (37/361)
*On-treatment failure includes subjects who met a protocol-defined virologic stopping rule or who had detectable HCV-RNA at the time of their last dose of INCIVEK and subjects who had viral breakthrough on peginterferon alfa/ribavirin.
†Relapse rates are calculated with a denominator of subjects with undetectable HCV-RNA at the end of treatment.
‡Other includes subjects with detectable HCV-RNA at the time of their last study dru |
