Six and eight-week regimens of simeprevir, daclatasvir, and sofosbuvir proved highly effective for treatment-naive patients with hepatitis C virus (HCV) genotype 1 (GT1) and early-stage liver fibrosis or compensated cirrhosis, according to a study published in the Journal of Viral Hepatitis.
ACCORDION (ClinicalTrials.gov Identifier: NCT02349048) was a phase 2, open-label, multicenter study conducted at 8 sites in the United States and Canada between January 21, 2015, and May 5, 2016. Participant eligibility was based on the following criteria: confirmed chronic HCV GT1 infection with early-stage liver fibrosis or compensated cirrhosis, a body mass index of 18 kg/m2 to 35 kg/m2, plasma HCV RNA >10 000 IU/mL at screening, naive to treatment for HCV, and eligible for treatment with pegylated interferon and ribavirin. Study participants with early-stage fibrosis were given simeprevir 150 mg, daclatasvir 60 mg, and sofosbuvir 400 mg once daily for 6 weeks, and participants with compensated cirrhosis were given the same regimen for 8 weeks.
The study aimed for a sample size of 60 participants in the 6-week group and 30 in the 8-week group, but only 68 patients met the stipulated FibroSURE™ and APRI [aspartate aminotransferase to platelet ratio index] score cut-offs in the study protocol. As a result, there were 59 patients included in the 6-week group and 9 patients in the 8-week group.
The primary study end point was sustained virologic response 12 weeks following treatment (SVR12) as evidenced by HCV RNA <15 IU/mL detected or not detected at that time point. The majority of patients with early-stage liver fibrosis (51/59, 86.4% [95% CI, 75-94]) and all patients with compensated cirrhosis (9/9, 100%) achieved SVR12. Of the 8 patients with early-stage fibrosis who did not achieve SVR12, 7 experienced posttreatment relapse and 1 discontinued the study prematurely due to incarceration.
Triple direct-acting antiviral treatment with simeprevir, daclatasvir, and sofosbuvir proved generally safe and well tolerated, and there were no treatment discontinuations due to an adverse event. Study limitations include the open-label design and the small number of participants, particularly the number of patients with compensated cirrhosis.
The study investigators conclude by stating that both treatment durations were associated with high SVR rates. “By combining three DAAs with different mechanisms of action into one treatment regimen, it is possible to elicit an early and sustained virologic response, allowing durations of treatment as short as 6 weeks in patients without cirrhosis which could be associated with improved medication adherence and patient quality of life.”
Disclosure: This study was funded by Janssen Research & Development. The writing of this paper was funded in part by Janssen Research & Development.
Sulkowski MS, Feld JJ, Lawitz E, et al. Efficacy and safety of 6 or 8 weeks of simeprevir, daclatasvir, sofosbuvir for HCV genotype 1 infection [published online December 23, 2017]. J Viral Hepat. doi:10.1111/jvh.12853