Stefan Zeuzem1, Ira M Jacobson, Tolga Baykal, Rui T Marinho, Fred Poordad, Marc Bourlière, Mark S 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. 1. From Johann Wolfgang Goethe University, Frankfurt am Main (S.Z.), and Medizinische Hochschule Hannover, Hannover (H.W.) - both in Germany; Weill Cornell Medical College, New York (I.M.J.), and Premier Medical Group of the Hudson Valley, Poughkeepsie (P.V.) - both in New York; AbbVie, North Chicago (T.B., J.X., T.P.-M., B.D.-T., L.L., T.P., B.B.), and Center for Liver Diseases, University of Chicago Medical Center, Chicago (D.M.J.) - both in Illinois; Centro Hospitalar de Lisboa Norte and Medical School of Lisbon, Lisbon, Portugal (R.T.M.); Texas Liver Institute, University of Texas Health Science Center, San Antonio (F.P.); Hôpital Saint Joseph, Marseille, France (M.B.); Johns Hopkins University, Baltimore (M.S.S.); Liver and Intestinal Research Centre, Vancouver, BC, Canada (E.T.); St. Vincent's Hospital (Melbourne), Fitzroy, Australia (P.D.); Saint Louis University, St. Louis (A.M.D.); and Southern California Liver Centers and Southern California Research Center, Coronado (T.H.).
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 withpeginterferon-ribavirin. METHODS: We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated withpeginterferon-ribavirinand 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 <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. CONCLUSIONS: Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response. (Funded by AbbVie; SAPPHIRE-II ClinicalTrials.gov number, NCT01715415.).
RCT Entities:
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 <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. CONCLUSIONS: Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response. (Funded by AbbVie; SAPPHIRE-II ClinicalTrials.gov number, NCT01715415.).
Authors: Cindy J Bednasz; Joshua R Sawyer; Anthony Martinez; Patrick G Rose; Samantha S Sithole; Holly R Hamilton; Farzia S Kaufman; Charles S Venuto; Qing Ma; Andrew Talal; Gene D Morse Journal: Future Virol Date: 2015 Impact factor: 1.831