title: Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial.
abstract: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients.
  
  
  
  We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12).
  
  
  
  After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events.
  
  
  
  In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.
authors.affiliation: Auckland Clinical Studies, Auckland, New Zealand. Electronic address: edgane@adhb.govt.nz.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.affiliation: Swedish Medical Center, Seattle, Washington.
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.affiliation: Indianapolis Gastroenterology Research Foundation, Indianapolis, Indiana.
authors.forename: David
authors.initials: D
authors.lastname: Pound
authors.affiliation: Christchurch Hospital and University of Otago, Christchurch, New Zealand.
authors.forename: Catherine A M
authors.initials: CA
authors.lastname: Stedman
authors.affiliation: Digestive CARE-South Florida Center of Gastroenterology, Wellington, Florida.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Davis
authors.affiliation: Borland-Groover Clinic, Jacksonville, Mississippi.
authors.forename: Kyle
authors.initials: K
authors.lastname: Etzkorn
authors.affiliation: Henry Ford Hospital and Health System, Detroit, Michigan.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: North Shore/Long Island Jewish PRIME, Manhasset, New York.
authors.forename: David
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: University of Colorado, Aurora, Colorado.
authors.forename: Gregory
authors.initials: G
authors.lastname: Everson
authors.affiliation: Fundación De Investigación De Diego, San Juan, Puerto Rico.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.affiliation: Queens Liver Center, Honolulu, Hawaii.
authors.forename: Naoky
authors.initials: N
authors.lastname: Tsai
authors.affiliation: Digestive Health Specialists, Winston-Salem, North Carolina.
authors.forename: Omer
authors.initials: O
authors.lastname: Khalid
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Sophia
authors.initials: S
authors.lastname: Lu
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Hadas
authors.initials: H
authors.lastname: Dvory-Sobol
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Stamm
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Huntington Medical Research Institutes Liver Center, Pasadena, California.
authors.forename: Myron
authors.initials: M
authors.lastname: Tong
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Beavers
authors.affiliation: Cumberland Research Associates, LLC, Fayetteville, Georgia.
authors.forename: John E
authors.initials: JE
authors.lastname: Poulos
authors.affiliation: Indiana University School of Medicine, Indiana.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Kwo
authors.affiliation: Stanford University Medical Center, Palo Alto, California.
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use*; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D047029:Lactams, Macrocyclic; D007930:Leucine / Q000031:analogs & derivatives; D047028:Macrocyclic Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D011810:Quinoxalines; D057057:Serine Proteases; D000069474:Sofosbuvir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins; D055815:Young Adult; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D006576:Heterocyclic Compounds, 4 or More Rings; D047029:Lactams, Macrocyclic; D007930:Leucine; D047028:Macrocyclic Compounds; D011392:Proline; D011810:Quinoxalines; D057057:Serine Proteases; D000069474:Sofosbuvir; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C000619503:voxilaprevir; C000614516:NS3-4A serine protease, Hepatitis C virus; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans
keywords: Clinical Trial; DAA; Direct-Acting Antiviral; Non-Genotype 1 HCV