centre, open-label trial conducted exclusively in 380 genotype 1-infected subjects with compensated cirrhosis (Child-Pugh A) who were either treatment-naïve or did not achieve SVR with prior treatment with pegIFN/RBV. Exviera and ombitasvir/paritaprevir/ritonavir in combination with ribavirin were administered for either 12 or 24 weeks of treatment.
Treated subjects (N=380) had a median age of 58 years (range: 21 to 71); 42.1% were treatment-naïve, 36.1% were prior pegIFN/RBV null responders; 8.2% were prior pegIFN/RBV partial responders, 13.7% were prior pegIFN/RBV relapsers; 70.3% were male; 3.2% were Black; 28.4% had a body mass index of at least 30 kg/m2; 14.7% had platelet counts of less than 90 x 109/L; 49.7% had albumin less than 40 g/L; 86.1% had baseline HCV RNA levels of at least 800,000 IU/mL; 81.8% had IL28B non-CC genotype; 24.7% had a history of depression or bipolar disorder; 68.7% had HCV genotype 1a infection, 31.3% had HCV genotype 1b infection.
Table 12 shows the SVR12 rates for genotype 1-infected subjects with compensated cirrhosis who were treatment-naïve or previously treated with pegIFN/RBV.
Table 12. SVR12 for genotype 1-infected subjects with compensated cirrhosis who were treatment-naïve or previously treated with pegIFN/RBV
CI = confidence interval, VF = virologic failure
a. 97.5% confidence intervals are used for the primary efficacy endpoints (overall SVR12 rate); 95% confidence intervals are used for additional efficacy endpoints (SVR12 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 v
