Boceprevir for untreated chronic HCV genotype 1 infection

SPRINT-2 Investigators

Research output: Contribution to journalArticle

2129 Citations (Scopus)

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 leadin 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.)

Original languageEnglish (US)
Pages (from-to)1195-1206
Number of pages12
JournalNew England Journal of Medicine
Volume364
Issue number13
DOIs
StatePublished - Mar 31 2011

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Chronic Hepatitis C
Hepacivirus
Ribavirin
Genotype
Infection
Placebos
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
Therapeutics
Standard of Care
Protease Inhibitors
Double-Blind Method
Anemia
RNA
Control Groups
Sustained Virologic Response

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Boceprevir for untreated chronic HCV genotype 1 infection. / SPRINT-2 Investigators.

In: New England Journal of Medicine, Vol. 364, No. 13, 31.03.2011, p. 1195-1206.

Research output: Contribution to journalArticle

SPRINT-2 Investigators. / Boceprevir for untreated chronic HCV genotype 1 infection. In: New England Journal of Medicine. 2011 ; Vol. 364, No. 13. pp. 1195-1206.
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title = "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 leadin 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.)",
author = "{SPRINT-2 Investigators} and Fred Poordad and Jonathan McCone and Bacon, {Bruce R.} and Savino Bruno and Manns, {Michael P.} and Sulkowski, {Mark S.} and Jacobson, {Ira M.} and Reddy, {K. Rajender} and Goodman, {Zachary D.} and Navdeep Boparai and DiNubile, {Mark J.} and Vilma Sniukiene and Brass, {Clifford A.} and Albrecht, {Janice K.} and Bronowicki, {Jean Pierre} and L. Colombato and J. Curciarello and M. Silva and H. Tanno and R. Terg and M. Adler and P. Langlet and L. Lasser and F. Nevens and F. Anderson and R. Bailey and M. Bilodeau and C. Cooper and Feinman, {S. V.} and J. Heathcote and M. Levstik and A. Ramji and M. Sherman and S. Shafran and E. Yoshida and A. Achim and {Ben Ali}, S. and Bigard, {M. A.} and C. Bonny and M. Bourliere and N. Boyer-Darrigrand and V. Canva and P. Couzigou and {De Ledinghen}, V. and D. Guyader and C. Hezode and D. Larrey and M. Latournerie and P. Marcellin and Louis Lambiase",
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T1 - Boceprevir for untreated chronic HCV genotype 1 infection

AU - SPRINT-2 Investigators

AU - Poordad, Fred

AU - McCone, Jonathan

AU - Bacon, Bruce R.

AU - Bruno, Savino

AU - Manns, Michael P.

AU - Sulkowski, Mark S.

AU - Jacobson, Ira M.

AU - Reddy, K. Rajender

AU - Goodman, Zachary D.

AU - Boparai, Navdeep

AU - DiNubile, Mark J.

AU - Sniukiene, Vilma

AU - Brass, Clifford A.

AU - Albrecht, Janice K.

AU - Bronowicki, Jean Pierre

AU - Colombato, L.

AU - Curciarello, J.

AU - Silva, M.

AU - Tanno, H.

AU - Terg, R.

AU - Adler, M.

AU - Langlet, P.

AU - Lasser, L.

AU - Nevens, F.

AU - Anderson, F.

AU - Bailey, R.

AU - Bilodeau, M.

AU - Cooper, C.

AU - Feinman, S. V.

AU - Heathcote, J.

AU - Levstik, M.

AU - Ramji, A.

AU - Sherman, M.

AU - Shafran, S.

AU - Yoshida, E.

AU - Achim, A.

AU - Ben Ali, S.

AU - Bigard, M. A.

AU - Bonny, C.

AU - Bourliere, M.

AU - Boyer-Darrigrand, N.

AU - Canva, V.

AU - Couzigou, P.

AU - De Ledinghen, V.

AU - Guyader, D.

AU - Hezode, C.

AU - Larrey, D.

AU - Latournerie, M.

AU - Marcellin, P.

AU - Lambiase, Louis

PY - 2011/3/31

Y1 - 2011/3/31

N2 - 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 leadin 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.)

AB - 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 leadin 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.)

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U2 - 10.1056/NEJMoa1010494

DO - 10.1056/NEJMoa1010494

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JF - New England Journal of Medicine

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