Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1

Kris V. Kowdley, Eric Lawitz, Fred Poordad, Daniel E. Cohen, David R. Nelson, Stefan Zeuzem, Gregory T. Everson, Paul Kwo, Graham R. Foster, Mark Sulkowski, Wangang Xie, Tami Pilot-Matias, George Liossis, Lois Larsen, Amit Khatri, Thomas Podsadecki, Barry Bernstein

Research output: Contribution to journalArticle

Abstract

BACKGROUND: An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients. This study was designed to evaluate multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection who had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin. METHODS: In this phase 2b, open-label study with 14 treatment subgroups, 571 patients without cirrhosis who had not received treatment previously or who had not had a response to prior therapy were randomly assigned to a regimen of ABT-450/r, combined with ABT-267 or ABT-333 or both, for 8, 12, or 24 weeks and received at least one dose of therapy. All the subgroups but 1 also received ribavirin (dose determined according to body weight). The primary end point was sustained virologic response at 24 weeks after the end of treatment. The primary efficacy analysis compared rates between previously untreated patients who received three direct-acting antiviral agents and ribavirin for 8 weeks and those who received the same therapy for 12 weeks. RESULTS: Among previously untreated patients who received three direct-acting antiviral agents (with the ABT-450/r dose administered as 150 mg of ABT-450 and 100 mg of ritonavir) plus ribavirin, the rate of sustained virologic response at 24 weeks after treatment was 88% among those who received the therapy for 8 weeks and 95% among those who received the therapy for 12 weeks (difference, -7 percentage points; 95% confidence interval, -19 to 5; P = 0.24). The rates of sustained virologic response across all treatment subgroups ranged from 83 to 100%. The most frequent adverse events were fatigue, headache, nausea, and insomnia. Eight patients (1%) discontinued treatment owing to adverse events. CONCLUSIONS In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy. (Funded by AbbVie; ClinicalTrials.gov number, NCT01464827.)

Original languageEnglish (US)
Pages (from-to)222-232
Number of pages11
JournalNew England Journal of Medicine
Volume370
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Hepacivirus
Interferons
Genotype
Ribavirin
Ritonavir
Therapeutics
Antiviral Agents
Infection
Sleep Initiation and Maintenance Disorders
Protease Inhibitors
Nausea
Fatigue
Headache
Fibrosis
Body Weight

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kowdley, K. V., Lawitz, E., Poordad, F., Cohen, D. E., Nelson, D. R., Zeuzem, S., ... Bernstein, B. (2014). Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. New England Journal of Medicine, 370(3), 222-232. https://doi.org/10.1056/NEJMoa1306227

Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. / Kowdley, Kris V.; Lawitz, Eric; Poordad, Fred; Cohen, Daniel E.; Nelson, David R.; Zeuzem, Stefan; Everson, Gregory T.; Kwo, Paul; Foster, Graham R.; Sulkowski, Mark; Xie, Wangang; Pilot-Matias, Tami; Liossis, George; Larsen, Lois; Khatri, Amit; Podsadecki, Thomas; Bernstein, Barry.

In: New England Journal of Medicine, Vol. 370, No. 3, 2014, p. 222-232.

Research output: Contribution to journalArticle

Kowdley, KV, Lawitz, E, Poordad, F, Cohen, DE, Nelson, DR, Zeuzem, S, Everson, GT, Kwo, P, Foster, GR, Sulkowski, M, Xie, W, Pilot-Matias, T, Liossis, G, Larsen, L, Khatri, A, Podsadecki, T & Bernstein, B 2014, 'Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1', New England Journal of Medicine, vol. 370, no. 3, pp. 222-232. https://doi.org/10.1056/NEJMoa1306227
Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. New England Journal of Medicine. 2014;370(3):222-232. https://doi.org/10.1056/NEJMoa1306227
Kowdley, Kris V. ; Lawitz, Eric ; Poordad, Fred ; Cohen, Daniel E. ; Nelson, David R. ; Zeuzem, Stefan ; Everson, Gregory T. ; Kwo, Paul ; Foster, Graham R. ; Sulkowski, Mark ; Xie, Wangang ; Pilot-Matias, Tami ; Liossis, George ; Larsen, Lois ; Khatri, Amit ; Podsadecki, Thomas ; Bernstein, Barry. / Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 3. pp. 222-232.
@article{d2876d32b1a249c88cccd46348994488,
title = "Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1",
abstract = "BACKGROUND: An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients. This study was designed to evaluate multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection who had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin. METHODS: In this phase 2b, open-label study with 14 treatment subgroups, 571 patients without cirrhosis who had not received treatment previously or who had not had a response to prior therapy were randomly assigned to a regimen of ABT-450/r, combined with ABT-267 or ABT-333 or both, for 8, 12, or 24 weeks and received at least one dose of therapy. All the subgroups but 1 also received ribavirin (dose determined according to body weight). The primary end point was sustained virologic response at 24 weeks after the end of treatment. The primary efficacy analysis compared rates between previously untreated patients who received three direct-acting antiviral agents and ribavirin for 8 weeks and those who received the same therapy for 12 weeks. RESULTS: Among previously untreated patients who received three direct-acting antiviral agents (with the ABT-450/r dose administered as 150 mg of ABT-450 and 100 mg of ritonavir) plus ribavirin, the rate of sustained virologic response at 24 weeks after treatment was 88{\%} among those who received the therapy for 8 weeks and 95{\%} among those who received the therapy for 12 weeks (difference, -7 percentage points; 95{\%} confidence interval, -19 to 5; P = 0.24). The rates of sustained virologic response across all treatment subgroups ranged from 83 to 100{\%}. The most frequent adverse events were fatigue, headache, nausea, and insomnia. Eight patients (1{\%}) discontinued treatment owing to adverse events. CONCLUSIONS In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy. (Funded by AbbVie; ClinicalTrials.gov number, NCT01464827.)",
author = "Kowdley, {Kris V.} and Eric Lawitz and Fred Poordad and Cohen, {Daniel E.} and Nelson, {David R.} and Stefan Zeuzem and Everson, {Gregory T.} and Paul Kwo and Foster, {Graham R.} and Mark Sulkowski and Wangang Xie and Tami Pilot-Matias and George Liossis and Lois Larsen and Amit Khatri and Thomas Podsadecki and Barry Bernstein",
year = "2014",
doi = "10.1056/NEJMoa1306227",
language = "English (US)",
volume = "370",
pages = "222--232",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "3",

}

TY - JOUR

T1 - Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1

AU - Kowdley, Kris V.

AU - Lawitz, Eric

AU - Poordad, Fred

AU - Cohen, Daniel E.

AU - Nelson, David R.

AU - Zeuzem, Stefan

AU - Everson, Gregory T.

AU - Kwo, Paul

AU - Foster, Graham R.

AU - Sulkowski, Mark

AU - Xie, Wangang

AU - Pilot-Matias, Tami

AU - Liossis, George

AU - Larsen, Lois

AU - Khatri, Amit

AU - Podsadecki, Thomas

AU - Bernstein, Barry

PY - 2014

Y1 - 2014

N2 - BACKGROUND: An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients. This study was designed to evaluate multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection who had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin. METHODS: In this phase 2b, open-label study with 14 treatment subgroups, 571 patients without cirrhosis who had not received treatment previously or who had not had a response to prior therapy were randomly assigned to a regimen of ABT-450/r, combined with ABT-267 or ABT-333 or both, for 8, 12, or 24 weeks and received at least one dose of therapy. All the subgroups but 1 also received ribavirin (dose determined according to body weight). The primary end point was sustained virologic response at 24 weeks after the end of treatment. The primary efficacy analysis compared rates between previously untreated patients who received three direct-acting antiviral agents and ribavirin for 8 weeks and those who received the same therapy for 12 weeks. RESULTS: Among previously untreated patients who received three direct-acting antiviral agents (with the ABT-450/r dose administered as 150 mg of ABT-450 and 100 mg of ritonavir) plus ribavirin, the rate of sustained virologic response at 24 weeks after treatment was 88% among those who received the therapy for 8 weeks and 95% among those who received the therapy for 12 weeks (difference, -7 percentage points; 95% confidence interval, -19 to 5; P = 0.24). The rates of sustained virologic response across all treatment subgroups ranged from 83 to 100%. The most frequent adverse events were fatigue, headache, nausea, and insomnia. Eight patients (1%) discontinued treatment owing to adverse events. CONCLUSIONS In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy. (Funded by AbbVie; ClinicalTrials.gov number, NCT01464827.)

AB - BACKGROUND: An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients. This study was designed to evaluate multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection who had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin. METHODS: In this phase 2b, open-label study with 14 treatment subgroups, 571 patients without cirrhosis who had not received treatment previously or who had not had a response to prior therapy were randomly assigned to a regimen of ABT-450/r, combined with ABT-267 or ABT-333 or both, for 8, 12, or 24 weeks and received at least one dose of therapy. All the subgroups but 1 also received ribavirin (dose determined according to body weight). The primary end point was sustained virologic response at 24 weeks after the end of treatment. The primary efficacy analysis compared rates between previously untreated patients who received three direct-acting antiviral agents and ribavirin for 8 weeks and those who received the same therapy for 12 weeks. RESULTS: Among previously untreated patients who received three direct-acting antiviral agents (with the ABT-450/r dose administered as 150 mg of ABT-450 and 100 mg of ritonavir) plus ribavirin, the rate of sustained virologic response at 24 weeks after treatment was 88% among those who received the therapy for 8 weeks and 95% among those who received the therapy for 12 weeks (difference, -7 percentage points; 95% confidence interval, -19 to 5; P = 0.24). The rates of sustained virologic response across all treatment subgroups ranged from 83 to 100%. The most frequent adverse events were fatigue, headache, nausea, and insomnia. Eight patients (1%) discontinued treatment owing to adverse events. CONCLUSIONS In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy. (Funded by AbbVie; ClinicalTrials.gov number, NCT01464827.)

UR - http://www.scopus.com/inward/record.url?scp=84892591928&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892591928&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1306227

DO - 10.1056/NEJMoa1306227

M3 - Article

C2 - 24428468

AN - SCOPUS:84892591928

VL - 370

SP - 222

EP - 232

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 3

ER -