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.).

• Authors: Fred Poordad, Jonathan McCone Jr, Bruce R Bacon, Savino Bruno, Michael P Manns, Mark S Sulkowski, Ira M Jacobson, K Rajender Reddy, Zachary D Goodman, Navdeep Boparai, Mark J DiNubile, Vilma Sniukiene, Clifford A Brass, Janice K Albrecht, Jean-Pierre Bronowicki, SPRINT-2 Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 364 Issue 13 Pg. 1195-206 (Mar 31 2011) ISSN: 1533-4406 [Electronic] United States
• PMID: 21449783 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• RNA, Viral
• Recombinant Proteins
• Serine Proteinase Inhibitors
• Polyethylene Glycols
• Ribavirin
• N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
• Proline
• peginterferon alfa-2b

Topics

• Adult
• Anemia (chemically induced)
• Antiviral Agents (adverse effects, therapeutic use)
• Black People
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (drug therapy, ethnology, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Proline (adverse effects, analogs & derivatives, therapeutic use)
• RNA, Viral (blood)
• Recombinant Proteins
• Ribavirin (therapeutic use)
• Serine Proteinase Inhibitors (adverse effects, therapeutic use)
• Treatment Outcome
• Viral Load