LONESTAR

LONESTAR Study: LDV/SOF ± RBV for genotype 1 - Phase II
Sofosbuvir and ledipasvir fi xed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial
Lawitz E. Lancet 2014;383:515-23

Anti-HCV
Ledipasvir
Sofosbuvir
Ribavirin
Genotype
1
1a
Treatment history
Naive
PI-experienced

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Design


* Liver biopsy with Metavir F4 or Ishak = 5
** Randomisation was stratified on genotype (1a or 1b) in both cohorts, and in addition on presence or absence of decompensated cirrhosis in cohort B

  • Co-formulated ledipasvir-sofosbuvir (LDV 90mg/SOF 400 mg) : 1 pill qd
  • 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 and patient disposition

SVR12 (HCV RNA < 25 IU/ mL ), % ( 95% CI)

Virologic failure

  • Virologic breaktrough : None
  • Post-treatment relapse
    • 1 in LDV/SOF 8W naïve group
    • 1 in LDV/SOF 12W experienced group
  • NS5A resistant variants
    • Baseline resistance in 9
    • 1 relapse (naïve) with baseline L31M and emergence of additional Y93H + Q30L + L31V at relapse ; emergence also of S282T (SOF-resistance)
    • 1 relapse (experienced) with Q30H + Y93H at baseline and relapse. No detection of S282T

Adverse events

  • Serious adverse events : 4 (4%) patients
  • No discontinuation for adverse event
  • Highest rates of adverse events in the RBV groups
  • Most common adverse events :
    • Nausea,
    • Anemia (only in RBV groups),
    • Upper respiratory tract infection,
    • Headache
  • Dose reduction of RBV in 8 patients, because of anemia
  • No Grade 2-4 liver chemistry abnormalities detected

Summary

  • In this pilot phase II randomised, open-label study, treatment with the fixed-dose combination of SOF and LDV with and without RBV was well tolerated and resulted in high rates of SVR12 (95–100%) in both treatment-naive and previously treated patients with genotype-1 HCV
    • SVR12 was similar with 8 and 12 weeks of LDV/SOF in naïve patients
  • 2 relapses occurred in patients with baseline NS5A variants
  • There was no clinically significant treatment-emergent safety issues
  • Limitations
    • Small size
    • Study not powered