GS-9451/GS-9256 Failure Study

GS-9451/GS-9256 Failure Study: SOF + PEG-IFN + RBV for genotype 1 and prior failure to DAA
Sofosbuvir Plus Pegylated Interferon and Ribavirin in Patients With Genotype 1 Hepatitis C Virus in Whom Previous Therapy With Direct-Acting Antivirals Has Failed
Pol S. Hepatology 2015; 62:129-34

Anti-HCV
Sofosbuvir
Ribavirin
PEG-IFNα 2a
Genotype
Treatment history
IFN-Experienced
PI-experienced
Cirrhosis
No

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Design


* GS-9451 ( vedroprevir ) : 1st generation PI ; GS-9256 : 1st generation PI

  • SOF 400 mg : 1 pill qd
  • PEG-IFNα-2a 180 µg SC once weekly
  • 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

Outcome


Emergence of NS5B RAV at relapse : 1 patient with emergence of L159F and 1 with emergence of S282G ; no emergence of S282T

Adverse events

  • Serious adverse event : 1 (dysphagia , unrelated)
  • Discontinuation due to adverse event : 3 (PEG-IFN in 2, RBV in 1)
  • Most common adverse events :
    • Fatigue (43%)
    • Headache (35%)
    • Nausea (24%)
    • Neutropenia (23%)
    • Influenza-like illness (19%)
    • Myalgia (15%)
    • Pruritus (15%)
    • Rash (15%)
  • Grade 3 / grade 4 laboratory abnormalities : 41% / 10%
  • Mean decrease in hemoglobin : -2.8 g/dl

Summary

  • In this open-label study, 12 weeks of treatment with SOF + PEG- IFN + RBV resulted in a high rate of SVR12 in patients without cirrhosis who had not achieved SVR in previous trials involving PEG- IFN/RBV plus a protease inhibitor with and without other DAAs
    • Similar SVR12 by baseline patient characteristics
    • High efficacy regardless of baseline RAVs : benefit of using a different class (SOF)
  • Limitations
    • Small sample size
    • Uncontrolled design
    • Lack of patients with cirrhosis