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BROWSE SLIDES

Design

* Liver biopsy with Metavir F4 or Ishak = 5
** Randomisation was stratified on genotype (1a or 1b) in both cohorts, and in addition on presence or absence of decompensated cirrhosis in cohort B

• Co-formulated ledipasvir-sofosbuvir (LDV 90mg/SOF 400 mg) : 1 pill qd
• RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or = 75 kg)

Objective

• Primary endpoint : SVR₁₂ (HCV RNA < 25 IU/mL) by intention to treat, with 2-sided 95% CI, no statistical hypothesis

Baseline characteristics and patient disposition

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

Virologic failure

• Virologic breaktrough : None
• Post-treatment relapse
  • 1 in LDV/SOF 8W naïve group
  • 1 in LDV/SOF 12W experienced group
• NS5A resistant variants
  • Baseline resistance in 9
  • 1 relapse (naïve) with baseline L31M and emergence of additional Y93H + Q30L + L31V at relapse ; emergence also of S282T (SOF-resistance)
  • 1 relapse (experienced) with Q30H + Y93H at baseline and relapse. No detection of S282T

Adverse events

• Serious adverse events : 4 (4%) patients
• No discontinuation for adverse event
• Highest rates of adverse events in the RBV groups
• Most common adverse events :
  • Nausea,
  • Anemia (only in RBV groups),
  • Upper respiratory tract infection,
  • Headache
• Dose reduction of RBV in 8 patients, because of anemia
• No Grade 2-4 liver chemistry abnormalities detected

Summary

• In this pilot phase II randomised, open-label study, treatment with the fixed-dose combination of SOF and LDV with and without RBV was well tolerated and resulted in high rates of SVR₁₂ (95–100%) in both treatment-naive and previously treated patients with genotype-1 HCV
  • SVR₁₂ was similar with 8 and 12 weeks of LDV/SOF in naïve patients
• 2 relapses occurred in patients with baseline NS5A variants
• There was no clinically significant treatment-emergent safety issues
• Limitations
  • Small size
  • Study not powered