ere 25 mg 150 mg, 100 mg once daily in PEARL-I, while the dose of paritaprevir was 100 mg or 150 mg in study M12-536. Treatment duration was 12 weeks for treatment naïve subjects, 12-24 weeks for treatment experienced subjects and 24 weeks for subjects with cirrhosis. Overall, 107 of 113 subjects without cirrhosis and 147 of 155 subjects with cirrhosis achieved SVR12 after 12-24 weeks of treatment.
Viekirax with ribavirin & without dasabuvir was eva luated for 12 weeks in genotype 1 treatment naive and treatment experienced non-cirrhotic subjects in a phase 2 study M11-652 (AVIATOR). The doses of paritaprevir were 100 mg and 200 mg and ombitasvir 25 mg. Ribavirin was dosed based on weight (1000 mg – 1200 mg per day). Overall, 72 of 79 treatment-naive subjects (45 of 52 GT1a and 27 of 27 GT1b) and 40 of 45 treatment-experienced subjects (21 of 26 GT1a and 19 of 19 GT1b) achieved SVR12 after 12 weeks of treatment.
Impact of ribavirin dose adjustment on probability of SVR
In Phase 3 clinical trials, 91.5% of subjects did not require ribavirin dose adjustments during therapy. In the 8.5% of subjects who had ribavirin dose adjustments during therapy, the SVR rate (98.5%) was comparable to subjects who maintained their starting ribavirin dose throughout treatment.
Clinical Trial in subjects with HCV genotype 1 infection/HIV-1 co-infection
In an open-label clinical trial (TURQUOISE-I) the safety and efficacy of 12 or 24 weeks of treatment with Viekirax and dasabuvir and ribavirin was eva luated in 63 subjects with genotype 1 chronic hepatitis C co-infected with HIV-1. See section 4.2 for dosing recommendations in HCV/HIV-1 co-infected patients. Subjects were on a stable HIV-1 antiretroviral therapy (ART) regimen that included ritonavir-boosted atazanavir or raltegravir, co-administered with a backbone of tenofovir plus emtricitabine or lamivudine.
Treated subjects (N = 63) had a median age of 51 years (range: 31 to 69); 24% of subjects were Black; 81% of subjects had IL28B non-CC genotype; 19% of subjects had compensated cirrhosis; 67% of subjects were HCV treatment-naïve; 33% of subjects had failed prior treatment with pegIFN/RBV; 89% of subjects had HCV genotype 1a infection.
Table 15 shows the SVR12 rates for subjects with HCV genotype 1 infection and HIV-1 co-infection in TURQUOISE-I.
Table 15. SVR12 for HIV-1 co-infected Subjects in TURQUOISE-I
a. On-treatment VF was defined as confirmed HCV ≥ 25 IU/mL after HCV RNA < 25 IU/mL during treatment, confirmed 1 log10 IU/mL increase in HCV RNA from nadir, or HCV RNA persistently ≥ 25 IU/mL with at least 6 weeks of treatment.
b. Relapse was defined as confirmed HCV RNA ≥ 25 IU/mL post-treatment before or during SVR12 window among subjects with HCV RNA < 25 IU/mL at last observation during at least 11 weeks of treatment.
c. These virologic failures appear to have resulted from reinfection based on analyses of baseline and virologic failure samples
d. Other includes subjects not achieving SVR12 but not experiencing on-treatment VF or relapse (e.g. missing HCV RNA values in the SVR12 window).
In TURQUOISE-I, the SVR12 rates in HCV/HIV-1 co-infected subjects were consistent with SVR12 rates in the phase 3 trials of HCV mono-infected subjects. 7 of 7 subjects with genotype 1b infection and 51 of 56 subjects with genotype 1a infection achieved SVR12. 5 of 6 subjects with compensated cirrhosis in each arm achieved SVR12.
Clini
