AGATE-I

AGATE-I Study: OBV/PTV/r + RBV in genotype 4 with cirrhosis
AGATE-I Study – Part I: OBV/PTV/r + RBV in genotype 4 with cirrhosis
Asselah T. Lancet Gastroenterol Hepatol 2016;1:25-35 ; Asselah T. EASL 2016, Abs. SAT-278, J Hepatol 2016;64:S827

Anti-HCV
Paritaprevir/ritonavir
Ombitasvir
Ribavirin
Genotype
4
Treatment history
IFN-Experienced
Cirrhosis
Yes

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Design


* Randomisation was stratified by treatment history (experienced vs naive) and for treatment-experienced on prior non-response (null, partial, relapse)
** Metavir > 3 or Ishak > 4, or Fibrotest > 0.72 + APRI > 2 or Fibroscan = 14.6 kPa ; Child-Pugh score = 6

Treatment regimens

  • Co-formulated ombitasvir (OBV)/ paritaprevir (PTV)/ rironavir (r): 25/150/100 mg QD = 2 tablets
  • RBV: 1000 mg/day if < 75 kg, 1200 mg/day if = 75 kg (bid dosing)

Objective

  • SVR12, (HCV RNA < 25 IU/ml) > 95% power to detect superiority with a 2 sided 97.5% lower confidence bound > 67% (historical SVR 12 with PEG-IFN + RBV in genotype 4)

Baseline characteristics

SRV12 rates by treatment arm, ITT, % (97.5% CI)


Sensitivity analysis: SVR 12 excluding patients with premature discontinuation of study drug with no on-treatment failure or with missing follow-up data in SVR 12 window:

  • 98% (57/58) for 12 weeks group
  • 100% (60/60) for 16 weeks group

NS5A RAVs and impact on SVR12

  • At baseline, NS5A RAV in 36/116 (31%) patients
  • SRV12
    • 100% (80/80) if no baseline RAV
    • 97% (35/36) if baseline RAV
  • 1 patient in Arm A (12 weeks of therapy) did not achieve SVR 12
    • Genotype 4a
    • IL28B CT genotype
    • Fibroscan : 15.6 kPa
    • Prior relapse to PEG-IFN + RBV
    • At baseline: P58L NS5A RAV, no NS3 RAV
    • At failure: emergence of L28M + Y93H NS5A RAVs

Reasons for not achieving SVR12

Treatment-emergent adverse events

Summary

  • High SVR rates were achieved in patients with HCV genotype 4 infection and compensated cirrhosis with OBV/PTV/r + RBV administered for 12 weeks or 16 weeks: SVR 12 was 97% and 98%, respectively
    • Superiority to the historical control (PEG-IFN + RBV)
    • 16-week treatment seems to provide no added benefit for patients with HCV genotype 4 infection and compensated cirrhosis
  • No post-treatment relapses
  • OBV/PTV/r + RBV was well tolerated with no discontinuations due to adverse events
  • All serious adverse events were deemed not related to study drugs