title: A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1.
abstract: OBJECTIVE
  ABT-450 (combined with low-dose ritonavir, ABT-450/r) is a potent HCV NS3 protease inhibitor, and ABT-072 is a non-nucleoside NS5B polymerase inhibitor. The goal of this study was to evaluate the safety, tolerability, and efficacy of the peginterferon-free combination of ABT-450/r and ABT-072 with ribavirin in treatment-naïve patients with IL28B CC genotype, infected with HCV genotype 1.
  
  
  METHODS
  This was a phase 2a, multicenter, open-label, single-arm study in 11 treatment-naïve, non-cirrhotic HCV GT1-infected patients with IL28B rs12979860 genotype CC. Patients received ABT-450/r 150/100 mg once daily and ABT-072 400 mg once daily with weight-based ribavirin 1000-1200 mg/day dosed twice daily for 12 weeks.
  
  
  RESULTS
  Eight (73%) patients were male, 9 (82%) were Caucasian (including 3 who self-identified as Hispanic); mean baseline HCV RNA was 6.9 log₁₀ IU/ml (range 6.5-7.3 log₁₀ IU/ml). All 11 patients completed 12 weeks of treatment and maintained HCV RNA <25 IU/ml from weeks 4 through 12 of treatment. Ten patients (91%) achieved sustained virologic response 24 weeks post-treatment, with a second patient relapsing 36 weeks post-treatment. There were no deaths, serious or severe adverse events, or premature discontinuations. Adverse events were mostly mild and the most frequent were headache, fatigue, nausea, and dry skin.
  
  
  CONCLUSIONS
  A 12-week regimen of ABT-450/r and ABT-072 with ribavirin was well tolerated with 9/11 patients achieving sustained virologic response through 36 weeks of post-treatment observation. These findings suggest that peginterferon-free regimens may have the potential to cure a high proportion of HCV genotype 1-infected patients.
authors: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States.
authors: Eric
authors: E
authors: Lawitz
authors: Fred
authors: F
authors: Poordad
authors: Kris V
authors: KV
authors: Kowdley
authors: Daniel E
authors: DE
authors: Cohen
authors: Thomas
authors: T
authors: Podsadecki
authors: Sara
authors: S
authors: Siggelkow
authors: Lois
authors: L
authors: Larsen
authors: Rajeev
authors: R
authors: Menon
authors: Gennadiy
authors: G
authors: Koev
authors: Rakesh
authors: R
authors: Tripathi
authors: Tami
authors: T
authors: Pilot-Matias
authors: Barry
authors: B
authors: Bernstein
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D019438:Ritonavir / Q000008:administration & dosage*; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D000095022:Interferon Lambda; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D007372:Interferons; D007378:Interleukins; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011392:Proline; D011480:Protease Inhibitors; D012254:Ribavirin; D019438:Ritonavir; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C585405:paritaprevir