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Design

* Randomisation was stratified on genotype (1a or 1b)
** Liver biopsy with Metavir F4, or Fibrotest® > 0.75 + APRI > 2, or Fibroscan kPa > 14.6

• Co-formulated DCV/ASV/BCB 30/200/75 mg qd : 1 pill bid
• RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)

Objective

• Primary endpoint : SVR₁₂ (HCV RNA < 25 IU/ml), with 97.5% CI, significantly > 69%, rate of historical control (composite of SVR achieved in this population with approved direct-acting antivirals + PEG-IFN + RBV), 90% power

Baseline characteristics and patient disposition

SVR₁₂ (HCV RNA < 25 IU/ml), % (95% CI)

SVR₁₂ by sub-group

• Comparable according to age, sex, baseline HCV RNA level, and IL28B genotype
• Among the 35 prior null responders in the experienced cohort, 34 (97%) achieved SVR₁₂ 

Resistance analysis

• NS5A polymorphisms at positions 28, 30, 31, or 93 were detected at baseline in 15 of 149 patients (10%) with genotype 1a infection and 13 of 52 patients (25%) with genotype 1b infection
• 13/15 (87%) with genotype 1a and 13/13 with genotype 1b achieved SVR₁₂
• 2 patients, in the treatment-experienced group, relapsed : one had M28V at baseline and the other had Q30H and Y93H at baseline
• In genotype 1a, emergence of NS5A resistance variants in patients with virologic failure in 11/12 patients; of NS3 resistance variants in 10/12 patients (R155K) ; of NS5B resistance variants in 2 patients (P495)
• For the single relapse in genotype 1b, only NS5A-Y93H was detected at virologic failure, with no signature NS3 or NS5B resistance variants detected

Adverse events and laboratory abnormalities, n

Summary

• In this open-label, uncontrolled study, 12 weeks of the fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir, with or without RBV, achieved an overall SVR₁₂ rate of 93% in patients with genotype 1 infection and compensated cirrhosis
  • Among patients with genotype 1a infection
    • SVR₁₂ was achieved by 88% of those receiving the fixed-dose combination alone
    • and by 95% of those with RBV added to the regimen
  • However, the contribution of RBV to SVR₁₂ remains uncertain because of the small sample size
  • A 98% SVR₁₂ rate was achieved after 12 weeks of treatment in patients with genotype 1b infection and cirrhosis
• Overall, resistance variants at baseline were infrequent and did not appear to have an adverse effect on SVR₁₂ rates