title: Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial.
abstract: BACKGROUND
  Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed.
  
  
  OBJECTIVE
  To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6.
  
  
  METHODS
  Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766).
  
  
  METHODS
  48 U.S. sites.
  
  
  METHODS
  377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks.
  
  
  METHODS
  Sustained virologic response at 12 weeks (SVR12).
  
  
  RESULTS
  In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide.
  
  
  CONCLUSIONS
  The study was open-label, no inferential statistics were planned, and sample sizes were small.
  
  
  CONCLUSIONS
  Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6.
  
  
  BACKGROUND
  Gilead Sciences.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Mitchell N
authors.initials: MN
authors.lastname: Davis
authors.forename: David L
authors.initials: DL
authors.lastname: Wyles
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Nahass
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thuluvath
authors.forename: Kyle
authors.initials: K
authors.lastname: Etzkorn
authors.forename: Federico
authors.initials: F
authors.lastname: Hinestrosa
authors.forename: Myron
authors.initials: M
authors.lastname: Tong
authors.forename: Mordechai
authors.initials: M
authors.lastname: Rabinovitz
authors.forename: John
authors.initials: J
authors.lastname: McNally
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: Lingling
authors.initials: L
authors.lastname: Han
authors.forename: Brian
authors.initials: B
authors.lastname: Doehle
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Timothy
authors.initials: T
authors.lastname: Morgan
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.forename: Tram T
authors.initials: TT
authors.lastname: Tran
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D006576:Heterocyclic Compounds, 4 or More Rings; D000069474:Sofosbuvir; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans