rates in HCV genotype 1a and 1b-infected subjects).
b. 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.
c. Relapse was defined as confirmed HCV RNA ≥ 25 IU/mL post-treatment before or during SVR12 window among subjects with HCV RNA less than 25 IU/mL at last observation during at least 11 or 22 weeks of treatment, for subjects assigned to 12 or 24 weeks of treatment, respectively.
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).
Relapse rates in GT1a cirrhotic subjects by baseline laboratory values are presented in Table 13.
Table 13. TURQUOISE-II: relapse rates by baseline laboratory values after 12 and 24 weeks of treatment in subjects with genotype 1a infection and compensated cirrhosis
In subjects with all three favourable baseline laboratory values (AFP < 20 ng/mL, platelets ≥ 90 x 109/L, and albumin ≥ 35 g/L), relapse rates were similar in subjects treated for 12 or 24 weeks.
Pooled analyses of clinical trials
Durability of response
Overall, 660 subjects in Phase 2 and 3 clinical trials had HCV RNA results for both the SVR12 and SVR24 time points. Among these subjects, the positive predictive value of SVR12 on SVR24 was 99.8%.
Pooled efficacy analysis
In Phase 3 clinical trials, 1083 subjects (including 189 with compensated cirrhosis) received the recommended regimen for their HCV genotype 1 subtype, cirrhosis status and relevant baseline characteristics. Table 14 shows SVR rates for these subjects.
In subjects who received the recommended regimen, 97% achieved SVR overall (among which 189 subjects with compensated cirrhosis achieved 96% SVR), while 0.5% experienced virologic breakthrough and 1.3% experienced post-treatment relapse.
Table 14. SVR12 rates for recommended treatment regimens by patient population
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 Exviera and ombitasvir/paritaprevir/ritonavir 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-infe |
