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Design

*Randomisation was stratified on genotype subtype (1a or 1b) and IL28 (CC or non-CC)

• Co-formulated paritaprevir / rironavir (PTV/r) : 100/100 or 150/100 or 200/100 mg qd
• Ombitasvir (OBV) : 25 mg qd
• Dasabuvir (DSV) : 400 mg bid
• RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or = 75 kg)

Design

*Randomisation was stratified on genotype subtype (1a or 1b) and IL28 (CC or non-CC)

• Co-formulated paritaprevir / rironavir (PTV/r) : 100/100 or 150/100 or 200/100 mg qd
• Ombitasvir (OBV) : 25 mg qd ; Dasabuvir (DSV) : 400 mg bid
• RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or = 75 kg)

Objective

• Primary analysis : SVR₂₄ with two-sided 95% CI, of naïve patients PTV150/r + OBV + DSV + RBV 8 weeks vs 12 weeks, 80% power to detect a 24% difference between groups ( mITT analysis)

Baseline characteristics and patient disposition

SVR₂₄ (HCV RNA < 25 IU/ml)

• SVR₂₄ in naïve cohort genotype 1a (76-94%) vs 1b (96-100%); odds ratio : 0.087 [p = 0.0008])

Comparison of SVR₂₄ in Treatment -Naïve Patients, according to treatment Regimens

Resistance emergence

• No variants at relapse in 7/10 patients in the 8-week groups
• In the 12-week and 24-week groups, 31/32 samples at breakthrough or relapse showed emergence of resistant variants.
  Most common :
  • NS3 : position 168
  • NS5A : positions 28 and 30
  • NS5B : position 556

Adverse events

P/r : co-formulated paritaprevir / rironavir : 100/100 or 150/100 or 200/100 mg qd
O : ombitasvir ; D : dasabuvir ; R : ribavirin ; 8 : 8 weeks ; 12 : 12 weeks ; 24 : 24 weeks

Grade 3-4 laboratory abnormalities

• Grade 3 elevation of bilirubin , n = 11 (2%) with no concomitant AST/ALT elevation
• Grade 3 ALT elevation, n = 5 (1%), Grade 3-4 Triglycerides, n = 7 (1%), Anemia : 5%

Summary

• In this phase IIb study, all-oral regimens of antiviral agents and RBV were effective both in non-cirrhotic patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy
• Rates of SVR₂₄ ranged from 83% to 100%
• Among previously untreated patients, the rate of treatment failure was lower among those receiving the triple combination of paritaprevir /ritonavir + ombitasvir + dasabuvir + RBV for 12 weeks than among those who received the same regimen for 8 weeks and among those who received fewer agents; extending the treatment to 24 weeks offered no further benefit
  • Higher number of relapses in 3D + RBV 8 weeks vs 12 weeks
• Paritaprevir /ritonavir + ombitasvir + dasabuvir + RBV for 12 weeks was associated with SVR₂₄ of 93% in null responders to prior therapy
• For genotype 1b, all regimens led to SVR₂₄ of 94%-100% with only 1/24 relapse in the 8-week group