PMID- 25614962
OWN - NLM
STAT- MEDLINE
DCOM- 20150601
LR  - 20220408
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 61
IP  - 4
DP  - 2015 Apr
TI  - All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with 
      hepatitis C virus genotype 3 infection: ALLY-3 phase III study.
PG  - 1127-35
LID - 10.1002/hep.27726 [doi]
AB  - Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection 
      are limited, with the currently approved all-oral regimens requiring 24-week 
      treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3; 
      ClinicalTrials.gov: NCT02032901) evaluated the 12-week regimen of daclatasvir 
      (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF; 
      pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were 
      either treatment naive (n = 101) or treatment experienced (n = 51) and received 
      DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the 
      proportions of treatment-naive and treatment-experienced patients achieving a 
      sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12 
      rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naive and 
      treatment-experienced patients, respectively; no virological breakthrough was 
      observed, and >/=99% of patients had a virological response (VR) at the end of 
      treatment. SVR12 rates were higher in patients without cirrhosis (96%; 105 of 
      109) than in those with cirrhosis (63%; 20 of 32). Five of seven patients who 
      previously failed treatment with an SOF-containing regimen and 2 of 2 who 
      previously failed treatment with an alisporivir-containing regimen achieved 
      SVR12. Baseline characteristics, including gender, age, HCV-RNA levels, and 
      interleukin-28B genotype, did not impact virological outcome. DCV plus SOF was 
      well tolerated; there were no adverse events (AEs) leading to discontinuation and 
      only 1 serious AE on-treatment, which was unrelated to study medications. The few 
      treatment-emergent grade 3/4 laboratory abnormalities that were observed were 
      transient. CONCLUSION: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of 
      patients with genotype 3 infection without cirrhosis and was well tolerated. 
      Additional evaluation to optimize efficacy in genotype 3-infected patients with 
      cirrhosis is underway.
CI  - (c) 2015 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of 
      the American Association for the Study of Liver Diseases.
FAU - Nelson, David R
AU  - Nelson DR
AD  - University of Florida, Gainesville, FL.
FAU - Cooper, James N
AU  - Cooper JN
FAU - Lalezari, Jacob P
AU  - Lalezari JP
FAU - Lawitz, Eric
AU  - Lawitz E
FAU - Pockros, Paul J
AU  - Pockros PJ
FAU - Gitlin, Norman
AU  - Gitlin N
FAU - Freilich, Bradley F
AU  - Freilich BF
FAU - Younes, Ziad H
AU  - Younes ZH
FAU - Harlan, William
AU  - Harlan W
FAU - Ghalib, Reem
AU  - Ghalib R
FAU - Oguchi, Godson
AU  - Oguchi G
FAU - Thuluvath, Paul J
AU  - Thuluvath PJ
FAU - Ortiz-Lasanta, Grisell
AU  - Ortiz-Lasanta G
FAU - Rabinovitz, Mordechai
AU  - Rabinovitz M
FAU - Bernstein, David
AU  - Bernstein D
FAU - Bennett, Michael
AU  - Bennett M
FAU - Hawkins, Trevor
AU  - Hawkins T
FAU - Ravendhran, Natarajan
AU  - Ravendhran N
FAU - Sheikh, Aasim M
AU  - Sheikh AM
FAU - Varunok, Peter
AU  - Varunok P
FAU - Kowdley, Kris V
AU  - Kowdley KV
FAU - Hennicken, Delphine
AU  - Hennicken D
FAU - McPhee, Fiona
AU  - McPhee F
FAU - Rana, Khurram
AU  - Rana K
FAU - Hughes, Eric A
AU  - Hughes EA
CN  - ALLY-3 Study Team
LA  - eng
SI  - ClinicalTrials.gov/NCT02032901
GR  - UL1 TR001427/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150310
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  - E2OU15WN0N (Uridine Monophosphate)
RN  - HG18B9YRS7 (Valine)
RN  - LI2427F9CI (daclatasvir)
RN  - WJ6CA3ZU8B (Sofosbuvir)
SB  - IM
CIN - Turk J Gastroenterol. 2016 Jan;27(1):89-90. PMID: 26728866
CIN - Gastroenterology. 2016 May;150(5):1241-3. PMID: 27018182
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/*administration & dosage
MH  - Carbamates
MH  - Drug Therapy, Combination
MH  - Female
MH  - Genotype
MH  - Hepacivirus/*genetics
MH  - Hepatitis C/*drug therapy/*virology
MH  - Humans
MH  - Imidazoles/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Pyrrolidines
MH  - Sofosbuvir
MH  - Time Factors
MH  - Uridine Monophosphate/administration & dosage/*analogs & derivatives
MH  - Valine/analogs & derivatives
MH  - Young Adult
PMC - PMC4409820
EDAT- 2015/01/24 06:00
MHDA- 2015/06/02 06:00
PMCR- 2015/04/25
CRDT- 2015/01/24 06:00
PHST- 2014/12/10 00:00 [received]
PHST- 2015/01/21 00:00 [accepted]
PHST- 2015/01/24 06:00 [entrez]
PHST- 2015/01/24 06:00 [pubmed]
PHST- 2015/06/02 06:00 [medline]
PHST- 2015/04/25 00:00 [pmc-release]
AID - 10.1002/hep.27726 [doi]
PST - ppublish
SO  - Hepatology. 2015 Apr;61(4):1127-35. doi: 10.1002/hep.27726. Epub 2015 Mar 10.