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Design

Objective

• Primary endpoint : SVR₂₄ (HCV RNA < 12 IU/ml), by per-protocol analysis (patients with > 8 weeks of treatment)
• Modelling viral kinetics, pharmacokinetics and pharmacodynamics (20 patients)

Baseline characteristics and disposition, median or %

SVR₂₄ (HCV RNA < 25 IU /ml) in Part 2, % (95% CI)

Bivariate model of baseline characteristics associated with relapse

Viral kinetic model

• No differences in viral decay based on RBV dose or baseline characteristics
• Fully fitted PK-viral kinetics model (10 patients on weight-based RBV and 10 patients on low-dose RBV) : significantly slower loss rate of free virus (clearance) in relapsers than participants who achieved SVR (clearance : 3.57 vs 5.60 per day; p = 0.009)

Histologic response

• 29 paired liver biopsies
  • Improvement in inflammation in 27 (93%)

Adverse events and laboratory abnormalities, n (%)

Summary

• In a population of patients with chronic HCV infection with genotype 1 with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of SOF + weight-based or low-dose RBV resulted in SVR₂₄ rates of 68% and 48%, respectively
• The viral kinetics-pharmacodynamics model demonstrated a significantly slower loss rate of infectious virus in participants who subsequently relapsed.
  • the mechanism of incomplete clearance of HCV and relapse in these participants remains elusive
• Limitations
  • relatively small sample size
  • higher, though small, increase in the number of discontinuations with low-dose RBV