FISSION

FISSION Study: SOF + RBV vs PEG-IFN╬▒-2a + RBV for HCV genotype 2 and 3
Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection
Lawitz E. NEJM 2013;368:1878-87

Anti-HCV
Sofosbuvir
Ribavirin
Genotype
2
3
Treatment history
Naive
Cirrhosis
Yes
No

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Design


* Randomisation was stratified on cirrhosis ( presence or absence), genotype (2 or 3) and HCV RNA (< or = 6 log 10 IU/ml)

  • SOF : 400 mg qd
  • PEG-IFNα-2a : 180 m g SC once weekly
  • RBV weight based ( bid dosing ) : 1000 mg/ day if < 75 kg or 1200 mg/ day if = 75 kg
  • RBV fixed-dose : 400 mg bid

Objective

  • Non inferiority of SOF + RBV : SVR12 ( 2-sided significance level of 5%, lower margin of the 95% CI for the difference = -15%, 95% power)

Baseline characteristics and patient disposition


* Excluded from efficacy analysis

HCV RNA < 25 IU/ml

Virologic breakthrough during treatment

  • 1 in SOF + RBV group vs 18 (7%) in PEG-IFN + RBV group

Relapse in patients with HCV RNA < 25 IU/ml at end of completed treatment

  • 74 / 24 9 ( 30 %) in SOF + RBV group vs 46/217 (21%) in PEG-IFN + RBV group

Multivariate analysis of factors associated with SVR12 in SOF + RBV group

Resistance testing (sequencing) in SOF + RBV group

  • 74 relapses :
    • No SOF-associated mutation (S282T)
    • No change in susceptibility to SOF in patients with NS5B substitutions

Adverse events , n (%)

Summary

  • In this open-label, randomised trial of previously untreated patients with genotype 2 or 3 infection, the rate SVR12 was the same among patients who were assigned 12 weeks of SOF + RBV or 24 weeks of PEG-IFN + RBV (67% in each group)
    • In genotype 2, SVR12 was higher with SOF + RBV (97% vs 78%)
    • In genotype 2, SVR12 was similarly low in both groups (56% vs 63%)
  • SOF + RBV was associated with fewer adverse events than PEG-IFN + RBV
    • Influenza-like constitutional symptoms and neuropsychiatric events were less common among patients receiving SOF + RBV than among those receiving PEG-IFN + RBV.
    • Although the rates of anemia was similar in both groups, neutropenia and thrombocytopenia were not observed in the SOF + RBV group
  • No virologic resistance was detected in patients who did not have a sustained virologic response