The role of directly acting antiviral agents in an interferon-free regimen for the treatment of chronic Hepatitis C infections needs to be evaluated in different populations.
To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin in a population with unfavorable traditional treatment predictors.
Design, Setting, and Patients
Single center, randomized, two-part, open-label phase 2a trial of 60 HCV genotype-1, treatment naive participants were enrolled at the National Institutes of Health, between October 2011 and April 2012.
In part 1, ten participants with early-moderate liver fibrosis were treated with 400mg daily of sofosbuvir and weight-based ribavirin (1000mg/daily if ≤ 75kg or 1200mg/daily if >75kg) for 24 weeks. In part 2, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive sofosbuvir with either weight-based or low-dose 600mg daily ribavirin for 24 weeks.
Main Outcome Measures
The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (SVR24).
In part 1, 9 (90%, 95% CI, 55% - 100%) achieved SVR24. In part 2, seven (28%) participants on weight-based ribavirin and ten (40%) participants on low-dose ribavirin relapsed leading to SVR24 rates of 68% (95% CI: 46%-85%) and 48%(95% CI 28%-69%) respectively (p=0.251) A fitted pharmacokinetic-viral kinetic model demonstrated a slower loss rate of infectious virus in relapsers. In bivariable analysis, male gender, advanced liver fibrosis and high baseline HCV RNA were associated with relapse. The regimen was safe and well tolerated with no discontinuations due to adverse events.
Conclusion and Relevance
A combination of sofosbuvir and weight-based ribavirin resulted in a high rate of sustained virologic response in a population traditionally considered difficult to treat. Male gender, advanced liver fibrosis and high baseline HCV RNA were identified as predictors of relapse to this interferon-free, HCV treatment.
clinicaltrials.gov identifier: NCT01441180.