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Hepatology. 2016 May;63(5):1430-41. doi: 10.1002/hep.28473. Epub 2016 Mar 4.

Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+).

Author information

  • 1Clinique Universitaire d'Hepato-Gastroentérologie, Pôle Digidune, CHU de Grenoble and Unité INSERM/Université Grenoble Alpes U823, IAPC Institut Albert Bonniot, Grenoble, France.
  • 2Austin Hospital, Heidelberg, Australia.
  • 3INSERM U954, CHU de Nancy, Université de Lorraine, Nancy, France.
  • 4St. Vincent's Hospital and Kirby Institute, UNSW Australia, Sydney, Australia.
  • 5CHU Henri Mondor, Créteil, France.
  • 6Monash Medical Centre, Clayton, Australia.
  • 7Hôpital Cochin, Paris, France.
  • 8Gallipoli Medical Research Foundation, Greenslopes, Australia.
  • 9South Australia Health, Adelaide, Australia.
  • 10Bristol-Myers Squibb Research & Development, Wallingford, CT.
  • 11Bristol-Myers Squibb Research & Development, Princeton, NJ.
  • 12St Vincent's Hospital and the University of Melbourne, Melbourne, Australia.

Abstract

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-naïve (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.

PMID:
26822022
PMCID:
PMC5069621
DOI:
10.1002/hep.28473
[PubMed - indexed for MEDLINE]
Free PMC Article
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