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

Jordan J. Feld, Kris V. Kowdley, Eoin Coakley, Samuel H. Sigal, David R. Nelson, Darrell Crawford, Ola Weiland, Humberto Aguilar, Junyuan Xiong, Tami Pilot-Matias, Barbara DaSilva-Tillmann, Lois Larsen, Thomas Podsadecki, Barry Bernstein

Research output: Contribution to journalArticle

650 Citations (Scopus)

Abstract

BACKGROUND: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the non-nucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of 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 (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78%) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B. RESULTS: A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A. The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6% in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B. CONCLUSIONS: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.

Original languageEnglish (US)
Pages (from-to)1594-1603
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number17
DOIs
StatePublished - 2014
Externally publishedYes

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Ritonavir
Ribavirin
Hepacivirus
Genotype
Therapeutics
Infection
Fibrosis
ABT-333
ABT-450
ABT-267
Placebos
Asthenia
Sleep Initiation and Maintenance Disorders
Pruritus
Protease Inhibitors
Treatment Failure
Nausea
Interferons
Tablets
Diarrhea

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Feld, J. J., Kowdley, K. V., Coakley, E., Sigal, S. H., Nelson, D. R., Crawford, D., ... Bernstein, B. (2014). Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. New England Journal of Medicine, 370(17), 1594-1603. https://doi.org/10.1056/NEJMoa1315722

Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. / Feld, Jordan J.; Kowdley, Kris V.; Coakley, Eoin; Sigal, Samuel H.; Nelson, David R.; Crawford, Darrell; Weiland, Ola; Aguilar, Humberto; 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. 1594-1603.

Research output: Contribution to journalArticle

Feld, JJ, Kowdley, KV, Coakley, E, Sigal, SH, Nelson, DR, Crawford, D, Weiland, O, Aguilar, H, Xiong, J, Pilot-Matias, T, DaSilva-Tillmann, B, Larsen, L, Podsadecki, T & Bernstein, B 2014, 'Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin', New England Journal of Medicine, vol. 370, no. 17, pp. 1594-1603. https://doi.org/10.1056/NEJMoa1315722
Feld, Jordan J. ; Kowdley, Kris V. ; Coakley, Eoin ; Sigal, Samuel H. ; Nelson, David R. ; Crawford, Darrell ; Weiland, Ola ; Aguilar, Humberto ; Xiong, Junyuan ; Pilot-Matias, Tami ; DaSilva-Tillmann, Barbara ; Larsen, Lois ; Podsadecki, Thomas ; Bernstein, Barry. / Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 17. pp. 1594-1603.
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abstract = "BACKGROUND: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the non-nucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of 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 (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78{\%}) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B. RESULTS: A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2{\%} (95{\%} confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2{\%} and 1.5{\%}, respectively, of the patients in group A. The response rates in group A were 95.3{\%} among patients with HCV genotype 1a infection and 98.0{\%} among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6{\%} in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5{\%} and 5.8{\%}, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5{\%} of the patients in group B. CONCLUSIONS: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.",
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TY - JOUR

T1 - Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin

AU - Feld, Jordan J.

AU - Kowdley, Kris V.

AU - Coakley, Eoin

AU - Sigal, Samuel H.

AU - Nelson, David R.

AU - Crawford, Darrell

AU - Weiland, Ola

AU - Aguilar, Humberto

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: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the non-nucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of 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 (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78%) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B. RESULTS: A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A. The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6% in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B. CONCLUSIONS: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.

AB - BACKGROUND: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the non-nucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-tablet coformulation of 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 (in doses determined according to body weight) (group A) or matching placebos (group B). The patients received the study treatment during a 12-week double-blind period. The primary end point was sustained virologic response at 12 weeks after the end of treatment. The primary analysis compared the response rate in group A with the response rate (78%) in a historical control group of previously untreated patients without cirrhosis who received telaprevir with peginterferon and ribavirin. Adverse events occurring during the double-blind period were compared between group A and group B. RESULTS: A total of 631 patients received at least one dose of the study drugs. The rate of sustained virologic response in group A was 96.2% (95% confidence interval, 94.5 to 97.9), which was superior to the historical control rate. Virologic failure during treatment and relapse after treatment occurred in 0.2% and 1.5%, respectively, of the patients in group A. The response rates in group A were 95.3% among patients with HCV genotype 1a infection and 98.0% among those with HCV genotype 1b infection. The rate of discontinuation due to adverse events was 0.6% in each study group. Nausea, pruritus, insomnia, diarrhea, and asthenia occurred in significantly more patients in group A than in group B (P<0.05 for all comparisons). Reductions in the hemoglobin level were all of grade 1 or 2; reductions of grade 1 and 2 occurred in 47.5% and 5.8%, respectively, of the patients in group A, whereas grade 1 reductions occurred in 2.5% of the patients in group B. CONCLUSIONS: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.

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