C-ISLE

C-ISLE study: EBR/GZR + SOF ± RBV in genotype 3 and cirrhosis

Foster GR. AASLD 2016, Abs. 74

Anti-HCV
Grazoprevir
Elbasvir
Sofosbuvir
Ribavirin
Genotype
3
Treatment history
Naive
IFN-Experienced
Cirrhosis
Yes

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Design


* Randomisation of treatment-experienced patients was stratified on prior relapse vs non relapse (partial, null, interferon-intolerant)
** Liver biopsy or Fibroscan® > 12.5 kPa

Objective

  • Primary endpoint: SVR12 (HCV RNA < 15 IU/mL), full analysis set (patients who received = 1 dose of study drug)

Baseline characteristics

SVR12 (FAS), %


* SVR12 = 100% in mFAS analysis, excluding patients who discontinued treatment for reasons unrelated to study medication (* lost to follow-up, ** consent withdrawal, *** discontinuation at D7 for cellulitis)

Resistance data

  • SVR12 according to baseline NS5A RAVs (15% sensitivity threshold): NS5A polymorphisms at positions 24, 28, 30, 31, 32, 38, 58, 62, 92, or 93)
    • 98% (48/49) if RAVs
    • 98% (46/47) if no RAVs
    • If Y93H present (N = 4): SVR12 = 0/1 (relapse) if 8 weeks treatment ; 3/3 (100%) if > 8 weeks treatment

2 relapses

  • Both patients received EBR/GZR/SOF + RBV for 8 weeks
    • No NS5A RAVS at baseline or failure in 1 patient
    • In 1 patient : NS5A RAVs at baseline : Y93H, P58, S62T ; at failure : P58 and S62T

Adverse events


* Lung infection, creatinine increased, chest pain, opiate overdose, and cellulitis
** 1 patient discontinued treatment at Day 7 due to cellulitis

Summary

  • High efficacy was demonstrated in treatment-naive and treatment-experienced cirrhotic HCV genotype 3-infected patients
    • There were no virologic failures among patients receiving EBR/GZR + SOF ± RBV for 12 or 16 weeks
  • Treatment duration longer than 12 weeks is not needed
  • High efficacy was seen regardless of
    • presence of baseline NS5A RAVs
    • or patient characteristics
  • Generally safe and well tolerated