PMID- 26822022
OWN - NLM
STAT- MEDLINE
DCOM- 20160908
LR  - 20231104
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 63
IP  - 5
DP  - 2016 May
TI  - Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and 
      advanced liver disease: A randomized phase III study (ALLY-3+).
PG  - 1430-41
LID - 10.1002/hep.28473 [doi]
AB  - Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with 
      advanced liver disease, are a challenging population in urgent need of optimally 
      effective therapies. The combination of daclatasvir (DCV; pangenotypic 
      nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural 
      protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in 
      noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated 
      DCV-SOF with ribavirin (RBV) in treatment-naive (n = 13) or treatment-experienced 
      (n = 37) genotype 3-infected patients with advanced fibrosis (n = 14) or 
      compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive 
      open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. 
      The primary endpoint was sustained virological response at post-treatment week 12 
      (SVR12). SVR12 (intention-to-treat) was 90% overall (45 of 50): 88% (21 of 24) in 
      the 12-week (91% observed) and 92% (24 of 26) in the 16-week group. All patients 
      with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% 
      overall (31 of 36): 83% (15 of 18) in the 12-week (88% observed) and 89% (16 of 
      18) in the 16-week group; for treatment-experienced patients with cirrhosis, 
      these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 
      14), respectively. One patient (12-week group) did not enter post-treatment 
      follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and 
      no virological breakthroughs. The most common adverse events (AEs) were insomnia, 
      fatigue, and headache. There were no discontinuations for AEs and no 
      treatment-related serious AEs. CONCLUSION: The all-oral regimen of DCV-SOF-RBV 
      was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of 
      treatment among genotype 3-infected patients with advanced liver disease, 
      irrespective of past HCV treatment experience.
CI  - (c) 2016 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of 
      the American Association for the Study of Liver Diseases.
FAU - Leroy, Vincent
AU  - Leroy V
AD  - Clinique Universitaire d'Hepato-Gastroenterologie, Pole Digidune, CHU de Grenoble 
      and Unite INSERM/Universite Grenoble Alpes U823, IAPC Institut Albert Bonniot, 
      Grenoble, France.
FAU - Angus, Peter
AU  - Angus P
AD  - Austin Hospital, Heidelberg, Australia.
FAU - Bronowicki, Jean-Pierre
AU  - Bronowicki JP
AD  - INSERM U954, CHU de Nancy, Universite de Lorraine, Nancy, France.
FAU - Dore, Gregory J
AU  - Dore GJ
AD  - St. Vincent's Hospital and Kirby Institute, UNSW Australia, Sydney, Australia.
FAU - Hezode, Christophe
AU  - Hezode C
AD  - CHU Henri Mondor, Creteil, France.
FAU - Pianko, Stephen
AU  - Pianko S
AD  - Monash Medical Centre, Clayton, Australia.
FAU - Pol, Stanislas
AU  - Pol S
AD  - Hopital Cochin, Paris, France.
FAU - Stuart, Katherine
AU  - Stuart K
AD  - Gallipoli Medical Research Foundation, Greenslopes, Australia.
FAU - Tse, Edmund
AU  - Tse E
AD  - South Australia Health, Adelaide, Australia.
FAU - McPhee, Fiona
AU  - McPhee F
AD  - Bristol-Myers Squibb Research & Development, Wallingford, CT.
FAU - Bhore, Rafia
AU  - Bhore R
AD  - Bristol-Myers Squibb Research & Development, Princeton, NJ.
FAU - Jimenez-Exposito, Maria Jesus
AU  - Jimenez-Exposito MJ
AD  - Bristol-Myers Squibb Research & Development, Princeton, NJ.
FAU - Thompson, Alexander J
AU  - Thompson AJ
AD  - St Vincent's Hospital and the University of Melbourne, Melbourne, Australia.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20160304
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antiviral Agents)
RN  - 0 (Carbamates)
RN  - 0 (Imidazoles)
RN  - 0 (Pyrrolidines)
RN  - 49717AWG6K (Ribavirin)
RN  - HG18B9YRS7 (Valine)
RN  - LI2427F9CI (daclatasvir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/*administration & dosage
MH  - Carbamates
MH  - Drug Resistance, Viral
MH  - Drug Therapy, Combination
MH  - Female
MH  - Genotype
MH  - Hepacivirus/*classification/genetics
MH  - Hepatitis C, Chronic/complications/*drug therapy/virology
MH  - Humans
MH  - Imidazoles/*administration & dosage/adverse effects
MH  - Liver Cirrhosis/*etiology
MH  - Male
MH  - Middle Aged
MH  - Pyrrolidines
MH  - Ribavirin/*administration & dosage/adverse effects
MH  - Sofosbuvir/*administration & dosage/adverse effects
MH  - Valine/analogs & derivatives
PMC - PMC5069621
EDAT- 2016/01/30 06:00
MHDA- 2016/09/09 06:00
PMCR- 2016/10/19
CRDT- 2016/01/30 06:00
PHST- 2015/12/22 00:00 [received]
PHST- 2016/01/20 00:00 [revised]
PHST- 2016/01/24 00:00 [accepted]
PHST- 2016/01/30 06:00 [entrez]
PHST- 2016/01/30 06:00 [pubmed]
PHST- 2016/09/09 06:00 [medline]
PHST- 2016/10/19 00:00 [pmc-release]
AID - HEP28473 [pii]
AID - 10.1002/hep.28473 [doi]
PST - ppublish
SO  - Hepatology. 2016 May;63(5):1430-41. doi: 10.1002/hep.28473. Epub 2016 Mar 4.