1Duke Clinical Research Institute, Duke University, Durham, North Carolina.
2Texas Liver Institute-University of Texas Health Science Center, San Antonio.
3Quest Clinical Research, San Francisco, California.
4University of Colorado School of Medicine, Denver.
5Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia6St Vincent's Hospital, Sydney, New South Wales, Australia.
6Quality Medical Research, Nashville, Tennessee.
7Gastrointestinal Specialists Of Georgia, Marietta.
8Indiana University School of Medicine, Indianapolis.
9Hôpital Henri Mondor, AP-HP, INSERM U955, Université Paris-Est, Créteil, France.
10Scripps Clinic, La Jolla, California.
11INSERM U1065, Team 8, Hepatic Complications in Obesity, Nice, France13Centre Hospitalier Universitaire of Nice, Digestive Center, Nice, France.
12Lehigh Valley Health Network, Allentown, Pennsylvania.
13University of Chicago Medical Center, Chicago, Illinois.
14University of British Columbia, Vancouver, British Columbia, Canada.
15Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, Australia.
16St Vincent's Hospital, Melbourne, Victoria, Australia19University of Melbourne, Melbourne, Victoria, Australia.
17Baylor College of Medicine, Houston, Texas.
18Kansas City Research Institute, Kansas City, Missouri.
19Inova Fairfax Hospital, Falls Church, Virginia.
20University of British Columbia, Victoria, British Columbia, Canada.
21Bristol-Myers Squibb, Princeton, New Jersey.
22Bristol-Myers Squibb, Wallingford, Connecticut.
Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis.
All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis.
DESIGN, SETTING, AND PARTICIPANTS:
The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses were based on historical controls; there were no internal controls.
All patients received twice-daily treatment with the fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg). In addition, patients within each cohort were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double-blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo.
MAIN OUTCOMES AND MEASURES:
Sustained virologic response at posttreatment week 12 (SVR12).
One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. Enrolled patients were 88% white with a median age of 58 years (treatment-naive group) or 60 years (treatment-experienced group); 74% had genotype 1a infection. SVR12 rates were 98% (97.5% CI, 88.9%-100%) for patients in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the treatment-experienced group when ribavirin was included in the regimen. With the fixed-dose combination alone, response rates were 93% (97.5% CI, 85.4%-100.0%) for patients in the treatment-naive group and 87% (97.5% CI, 75.3%-98.0%) for those in the treatment-experienced group. Three serious adverse events were considered to be treatment related and there were 4 adverse event-related discontinuations. Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation.
CONCLUSIONS AND RELEVANCE:
In this open-label uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12.
Continued progress against hepatitis C infection. [JAMA. 2015]