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Design

* Liver biopsy with Metavir ≤ 3 or Ishak ≤ 4, or Fibrotest® ≤ 0.72 + APRI ≤ 2, or Fibroscan kPa < 9.6
** Randomisation stratified on prior PEG-IFN + RBV therapy response (null, partial, relapse) and on genotype subtype (1a or 1b)

Treatment regimens

• Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) : 25/150/100 mg qd = 2 tablets
• Dasabuvir (DSV) : 250 mg bid
• RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)

Objectives

• Non-inferiority and superiority of SVR₁₂ assessed vs estimated rate of SVR₁₂ with a telaprevir-based regimen in non-cirrhotic naïve patients : 78%; 95% CI : 75 to 80).
• A noninferiority margin of 10.5 % of the 95% CI for the SVR₁₂ of the new regimen established 70% as the noninferiority threshold; the superiority threshold was 80%.
• Analyses by mITT, power > 90%

Baseline characteristics and patient disposition

SVR₁₂ (HCV RNA < 25 IU /ml)

* 95% CI : 94.5 to 97.9 : noninferior and superior to the historical SVR₁₂ with TVR + PEG-IFN + RBV (78.0%)
** 95% CI : 93.0 to 97.6 : noninferior and superior to the historical SVR₁₂ with TVR + PEG-IFN + RBV (72.0%)
*** 95% CI : 95.8 to 100 : noninferior and superior to the historical SVR₁₂ with TVR + PEG-IFN + RBV (80.0%)

Virologic failure

• N = 1, at W12 (genotype 1a)

Relapse

• N = 7 (1.5%)
  • 5 by W4 post-treatment
  • 2 by W12

Resistance testing (population sequencing) of the 7 relapses + 1 failure

• All had ≥ 1 mutant resistant variants
  • Genotype 1a (N = 7) : D168V (N = 6) in NS3 ; M28T (N = 2) and Q30R(N = 3) in NS5A ; S556G (N = 3) in NS5B
  • Genotype 1b (N = 1) : Y56H + D168V (NS3), L31M + Y93H (NS5A) and S556G (NS5B)

Adverse events, N (%)

Summary

• Rates of response to a 12-week interferon-free combination regimen, of ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin, were more than 95% among previously untreated patients with HCV genotype 1 infection
• SVR₁₂ was non inferior and superior to the historical control rate with telaprevir plus PEG-IFN + RBV in a similar patient population
• SVR₁₂ was similar in patients with HCV genotype 1a or 1b infection, and in various subgroups (age, sex, fibrosis, IL28B)
• Tolerability was good, with
  • 0.6% of patients discontinuing for adverse event
  • Nausea, pruritus , insomnia, diarrhea, and asthenia more frequent in the active group
  • Low incidence of grade 3-4 bilirubin elevation
• In conclusion, a 12-week all-oral combination regimen of OBV/PTV/r + DSV + RBV resulted in SVR₁₂ > 95%, regardless of HCV genotype (1a or 1b) and with low rates of treatment discontinuation, in previously untreated patients with HCV genotype 1 infection and no cirrhosis