Boceprevir for untreated chronic HCV genotype 1 infection

Abstract

Background: Peginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies.

Methods: We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately.

Results: A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively.

Conclusions: The addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.).

Figure 1. Study Design

Patients in each of the two study cohorts were randomly assigned to a treatment group in a 1:1:1 ratio. All patients received peginterferon alfa-2b–ribavirin during the 4-week lead-in period. Subsequently, patients assigned to group 1 received 44 weeks of peginterferon alfa-2b–ribavirin as well as a placebo capsule; patients assigned to group 3 received peginterferon–ribavirin as well as boceprevir for 44 weeks; and patients assigned to group 2 received peginterferon–ribavirin as well as boceprevir for 24 weeks, and those with a detectable hepatitis C virus (HCV) RNA level at any visit between weeks 8 and 24 received peginterferon–ribavirin plus placebo from week 28 to week 48. Treatment was discontinued for reasons of futility if the HCV RNA level was detectable at the week 24 visit. Boceprevir was given for a total of 24 weeks in group 2 (irrespective of the rapidity of the decrease in the viral load) and, unless futility had been shown, for a total of 44 weeks in group 3. The x-axis numbers are not to scale.