Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection.
OBJECTIVE
The antiviral activity of all-oral, ribavirin-free, direct-acting antiviral regimens requires evaluation in patients with chronic hepatitis C virus (HCV) infection.


OBJECTIVE
To determine the rates of sustained virologic response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan-genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and beclabuvir (a nonnucleoside NS5B inhibitor).


METHODS
This was an open-label, single-group, uncontrolled international study (UNITY-1) conducted at 66 sites in the United States, Canada, France, and Australia between December 2013 and August 2014. Patients without cirrhosis who were either treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV genotype 1 infection were included.


METHODS
Patients received a twice-daily fixed-dose combination of daclatasvir, 30 mg; asunaprevir, 200 mg; and beclabuvir, 75 mg.


METHODS
The primary study outcome was SVR12 (HCV-RNA <25 IU/mL at posttreatment week 12) in patients naive to treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort.


RESULTS
Baseline characteristics were comparable between the treatment-naive and treatment-experienced cohorts. Patients were 58% male, 26% had IL28B (rs12979860) CC genotype, 73% were infected with genotype 1a, and 27% were infected with genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI, 88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%) and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%). Virologic failure occurred in 34 patients (8%) overall. One patient died at posttreatment week 3; this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (<1%) leading to treatment discontinuation, including 2 grade 4 alanine aminotransferase elevations. The most common adverse events (in ≥10% of patients) were headache, fatigue, diarrhea, and nausea.


CONCLUSIONS
In this open-label, nonrandomized, uncontrolled study, a high rate of SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic patients with chronic HCV genotype 1 infection who received 12 weeks of treatment with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir.


BACKGROUND
clinicaltrials.gov Identifier: NCT01979939.
Texas Liver Institute, University of Texas Health Science Center, San Antonio.
Fred
F
Poordad
Monash Health and Monash University, Melbourne, Australia.
William
W
Sievert
Fremantle Hepatitis Services, School of Medicine and Pharmacology, University of Western Australia, Fremantle, Australia.
Lindsay
L
Mollison
Medical Associates Research Group, San Diego, California.
Michael
M
Bennett
Royal Adelaide Hospital, Adelaide, Australia.
Edmund
E
Tse
James J. Peters Veterans Affairs Medical Center, Bronx, New York7Icahn School of Medicine at Mount Sinai, New York, New York.
Norbert
N
Bräu
Dean Foundation, Madison, Wisconsin.
James
J
Levin
University Gastroenterology, Providence, Rhode Island.
Thomas
T
Sepe
University of Calgary, Calgary, Alberta, Canada.
Samuel S
SS
Lee
Austin Hospital, Victoria, Australia.
Peter
P
Angus
Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada.
Brian
B
Conway
Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, INSERM UMS-20, Institut Pasteur, Paris, France.
Stanislas
S
Pol
Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
Nathalie
N
Boyer
INSERM U954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre les Nancy, France.
Jean-Pierre
JP
Bronowicki
Weill Cornell Medical College, New York, New York.
Ira
I
Jacobson
Duke University Medical Center, Durham, North Carolina.
Andrew J
AJ
Muir
University of Pennsylvania, Philadelphia.
K Rajender
KR
Reddy
LAIR Centre, Vancouver, British Columbia, Canada.
Edward
E
Tam
Fundacion de Investigacion, San Juan, Puerto Rico.
Grisell
G
Ortiz-Lasanta
Hôpital Du Haut-Leveque, Pessac, France.
Victor
V
de Lédinghen
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Mark
M
Sulkowski
Bristol-Myers Squibb, Princeton, New Jersey.
Navdeep
N
Boparai
Bristol-Myers Squibb, Wallingford, Connecticut.
Fiona
F
McPhee
Bristol-Myers Squibb, Princeton, New Jersey.
Eric
E
Hughes
Bristol-Myers Squibb, Wallingford, Connecticut.
E Scott
ES
Swenson
Bristol-Myers Squibb, Wallingford, Connecticut.
Philip D
PD
Yin
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001552:Benzazepines / Q000008:administration & dosage*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D013449:Sulfonamides / Q000008:administration & dosage*; D014633:Valine / Q000031:analogs & derivatives
C587012:8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide; D000998:Antiviral Agents; D001552:Benzazepines; D002219:Carbamates; D007093:Imidazoles; D007211:Indoles; D007546:Isoquinolines; D011759:Pyrrolidines; D013449:Sulfonamides; D000410:Alanine Transaminase; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir