Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt

Abstract

Objective: We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens.

Design: In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12).

Results: We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin.

Conclusion: Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir.

Trial registration number: NCT02487030.

Keywords: chronic hepatitis; cirrhosis; genotype.

Conflict of interest statement

Competing interests: GS has served as a principal investigator for AbbVie and Gilead. GE has served as a principal investigator for AbbVie, Gilead, BMS and Pharco Pharmaceuticals, and has served as a speaker for Gilead and BMS, and has served on advisory boards for Gilead and MSD. MH has served as an investigator for AbbVie, Janssen and Gilead, and has served as a speaker for AbbVie. RS has served as an investigator for AbbVie and Gilead. ME has served as an investigator for Gilead. RF has served as an investigator for Gilead, Abbie and Pharco Pharmaceuticals. AE has served as an investigator for Gilead, Abbvie and Janssen. RH declares no conflicts of interest. WA-R has served as a co-investigator for Gilead, Janssen and AbbVie. TZ has served as a co-investigator for Janssen and AbbVie. IW has served as an investigator, speaker and on advisory boards for AbbVie, Eva Pharma, Gilead, Janssen, Marcyrl, Onxio, Pharco and Roche. WD has served as an investigator for AbbVie, Janssen and Gilead. The following coauthors are employees of and hold stock interest in Gilead Sciences: KK, BM, AO, SL, DMB and JGMcH.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Patient disposition. OT, on-treatment.

Figure 2

Proportion of patients achieving SVR12. Error bars represent 95% CIs. All patients who did not achieve SVR12 experienced virological relapse except one treatment-naive patient who received LDV/SOF+RBV for 8 weeks (on-treatment virological failure), one treatment-naive patient who received LDV/SOF+RBV for 12 weeks (relapse after early discontinuation due to a serious adverse event) and one IFN experienced patient who received LDV/SOF for 12 weeks (achieved SVR4, but died prior to post-treatment follow-up week 12). IFN, interferon; LDV, ledipasvir; RBV, ribavirin; SOF, sofosbuvir; SVR12, sustained virological response at 12 weeks post-treatment.

Figure 3

Proportion of treatment-naive patients (A) and treatment-experienced patients (B) achieving SVR12 according to cirrhosis status. Error bars represent 95% CIs. All patients who did not achieve SVR12 experienced virological relapse except: one treatment-naive patient who received LDV/SOF+RBV for 8 weeks (on-treatment virological failure), one treatment-naive patient who received LDV/SOF+RBV for 12 weeks (relapse after early discontinuation due to a serious adverse event) and one IFN-experienced patient who received LDV/SOF for 12 weeks (achieved SVR4, but died prior to post-treatment follow-up week 12). EXP, experienced; IFN, interferon; LDV, ledipasvir; RBV, ribavirin; SOF, sofosbuvir; SVR12, sustained virological response at 12 weeks post-treatment.