Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin

Stefan Zeuzem, Ira M. Jacobson, Tolga Baykal, Rui T. Marinho, Fred Poordad, Marc Bourlier̀e, Mark Sulkowski, Heiner Wedemeyer, Edward Tam, Paul Desmond, Donald M. Jensen, Adrian M. Di Bisceglie, Peter Varunok, Tarek Hassanein, Junyuan Xiong, Tami Pilot-Matias, Barbara DaSilva-Tillmann, Lois Larsen, Thomas Podsadecki, Barry Bernstein

Research output: Contribution to journalArticle

Abstract

BACKGROUND: In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. METHODS: We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. RESULTS: A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P = 0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to

Original languageEnglish (US)
Pages (from-to)1604-1614
Number of pages11
JournalNew England Journal of Medicine
Volume370
Issue number17
DOIs
StatePublished - 2014

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Ritonavir
Retreatment
Ribavirin
ABT-450
ABT-333
ABT-267
Fibrosis
Genotype
Placebos
Recurrence
Pruritus
Infection

ASJC Scopus subject areas

  • Medicine(all)

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Zeuzem, S., Jacobson, I. M., Baykal, T., Marinho, R. T., Poordad, F., Bourlier̀e, M., ... Bernstein, B. (2014). Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. New England Journal of Medicine, 370(17), 1604-1614. https://doi.org/10.1056/NEJMoa1401561

Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. / Zeuzem, Stefan; Jacobson, Ira M.; Baykal, Tolga; Marinho, Rui T.; Poordad, Fred; Bourlier̀e, Marc; Sulkowski, Mark; Wedemeyer, Heiner; Tam, Edward; Desmond, Paul; Jensen, Donald M.; Di Bisceglie, Adrian M.; Varunok, Peter; Hassanein, Tarek; Xiong, Junyuan; Pilot-Matias, Tami; DaSilva-Tillmann, Barbara; Larsen, Lois; Podsadecki, Thomas; Bernstein, Barry.

In: New England Journal of Medicine, Vol. 370, No. 17, 2014, p. 1604-1614.

Research output: Contribution to journalArticle

Zeuzem, S, Jacobson, IM, Baykal, T, Marinho, RT, Poordad, F, Bourlier̀e, M, Sulkowski, M, Wedemeyer, H, Tam, E, Desmond, P, Jensen, DM, Di Bisceglie, AM, Varunok, P, Hassanein, T, Xiong, J, Pilot-Matias, T, DaSilva-Tillmann, B, Larsen, L, Podsadecki, T & Bernstein, B 2014, 'Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin', New England Journal of Medicine, vol. 370, no. 17, pp. 1604-1614. https://doi.org/10.1056/NEJMoa1401561
Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, Bourlier̀e M et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. New England Journal of Medicine. 2014;370(17):1604-1614. https://doi.org/10.1056/NEJMoa1401561
Zeuzem, Stefan ; Jacobson, Ira M. ; Baykal, Tolga ; Marinho, Rui T. ; Poordad, Fred ; Bourlier̀e, Marc ; Sulkowski, Mark ; Wedemeyer, Heiner ; Tam, Edward ; Desmond, Paul ; Jensen, Donald M. ; Di Bisceglie, Adrian M. ; Varunok, Peter ; Hassanein, Tarek ; Xiong, Junyuan ; Pilot-Matias, Tami ; DaSilva-Tillmann, Barbara ; Larsen, Lois ; Podsadecki, Thomas ; Bernstein, Barry. / Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 17. pp. 1604-1614.
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T1 - Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin

AU - Zeuzem, Stefan

AU - Jacobson, Ira M.

AU - Baykal, Tolga

AU - Marinho, Rui T.

AU - Poordad, Fred

AU - Bourlier̀e, Marc

AU - Sulkowski, Mark

AU - Wedemeyer, Heiner

AU - Tam, Edward

AU - Desmond, Paul

AU - Jensen, Donald M.

AU - Di Bisceglie, Adrian M.

AU - Varunok, Peter

AU - Hassanein, Tarek

AU - Xiong, Junyuan

AU - Pilot-Matias, Tami

AU - DaSilva-Tillmann, Barbara

AU - Larsen, Lois

AU - Podsadecki, Thomas

AU - Bernstein, Barry

PY - 2014

Y1 - 2014

N2 - BACKGROUND: In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. METHODS: We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. RESULTS: A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P = 0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to

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