Interferon-based treatment is not suitable for many patients with hepatitis C virus ( HCV ) infection because of contraindications such as psychiatric illness, and a high burden of adverse events.
LONESTAR, an open-label, randomised, phase 2 trial, has assessed the efficacy and safety of an Interferon-free regimen, a fixed-dose combination of the nucleotide polymerase inhibitor Sofosbuvir ( 400 mg ) and the HCV NS5A inhibitor Ledipasvir ( 90 mg ), with and without Ribavirin, in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen.
For this study, 100 adult patients ( 18 years or more ) with HCV infection at a Centre in the USA during the year 2012 were enrolled.
In cohort A, researchers have used a computer-generated sequence to randomly assign ( 1:1:1; stratified by HCV genotype [ 1a vs 1b ]) 60 non-cirrhotic, treatment-naive patients to receive Sofosbuvir plus Ledipasvir for 8 weeks ( group 1 ), Sofosbuvir plus Ledipasvir and Ribavirin for 8 weeks ( group 2 ), or Sofosbuvir plus Ledipasvir for 12 weeks ( group 3 ).
In cohort B, researchers randomly allocated ( 1:1; stratified by genotype and presence or absence of cirrhosis ) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive Sofosbuvir plus Ledipasvir for 12 weeks ( group 4 ) or Sofosbuvir plus Ledipasvir and Ribavirin for 12 weeks ( group 5 ). 22 ( 55% ) of 40 patients in cohort B had compensated cirrhosis.
The primary endpoint was sustained virological response 12 weeks after treatment ( SVR12 ), analysed by intention to treat.
In cohort A, SVR12 was achieved by 19 ( 95% ) of 20 patients in group 1, by 21 ( 100% ) of 21 patients in group 2, and by 18 ( 95% ) of 19 patients in group 3.
In cohort B, SVR12 was achieved by 18 ( 95% ) of 19 patients in group 4 and by all 21 ( 100% ) of 21 patients in group 5. Two patients had viral relapse; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment.
The most common adverse events were nausea, anaemia, upper respiratory tract infection, and headache. One patient in group five had a serious adverse event of anaemia, thought to be related to Ribavirin treatment.
These findings suggest that the fixed-dose combination of Sofosbuvir and Ledipasvir alone or with Ribavirin has the potential to cure most patients with genotype-1 HCV, irrespective of treatment history or the presence of compensated cirrhosis.
Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of Ribavirin. ( Xagena )
Lawitz E et al, The Lancet 2014; 383: 515-523