Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection.
OBJECTIVE
We performed a phase 2 clinical trial to evaluate the efficacy and safety of ledipasvir and sofosbuvir, with or without ribavirin, in patients infected with hepatitis C virus (HCV) genotype 3 or 6.


METHODS
We performed an open-label study of 126 patients with HCV genotype 3 or 6 infections at 2 centers in New Zealand from April 2013 through October 2014. Subjects were assigned 1 of 4 groups that received 12 weeks of treatment. Previously untreated patients with HCV genotype 3 were randomly assigned to groups given fixed-dose combination tablet of ledipasvir and sofosbuvir (n = 25) or ledipasvir and sofosbuvir along with ribavirin (n = 26). Treatment-experienced patients with HCV genotype 3 (n = 50) received ledipasvir and sofosbuvir and ribavirin. Treatment-naïve or treatment-experienced patients with HCV genotype 6 (n = 25) received ledipasvir and sofosbuvir. The primary end point was the percentage of patients with HCV RNA ≤15 IU/mL 12 weeks after stopping therapy (sustained virologic response at 12 weeks [SVR12]).


RESULTS
Among treatment-naïve genotype 3 patients, 16 of 25 (64%) receiving ledipasvir and sofosbuvir alone achieved SVR12 compared with all 26 patients (100%) receiving ledipasvir and sofosbuvir and ribavirin. Among treatment-experienced patients with HCV genotype 3, forty-one of fifty achieved an SVR12 (82%). Among patients with HCV genotype 6, the rate of SVR12 was 96% (24 of 25 patients). The most common adverse events were headache, upper respiratory infection, and fatigue. One patient with HCV genotype 3 discontinued ledipasvir and sofosbuvir because of an adverse event (diverticular perforation), which was not considered treatment related.


CONCLUSIONS
In an uncontrolled, open-label trial, high rates of SVR12 were achieved by patients with HCV genotype 3 infection who received 12 weeks of ledipasvir and sofosbuvir plus ribavirin, and by patients with HCV genotype 6 infection who received 12 weeks of sofosbuvir and ledipasvir without ribavirin. Current guidelines do not recommend the use of ledipasvir and sofosbuvir, with or without ribavirin, in patients with HCV genotype 3 infection. ClinicalTrials.gov Number: NCT01826981.
Auckland Clinical Studies Ltd., Auckland, New Zealand. Electronic address: edgane@adhb.govt.nz.
Edward J
EJ
Gane
Gilead Sciences, Inc., Foster City, California.
Robert H
RH
Hyland
Gilead Sciences, Inc., Foster City, California.
Di
D
An
Gilead Sciences, Inc., Foster City, California.
Evguenia
E
Svarovskaia
Gilead Sciences, Inc., Foster City, California.
Phillip S
PS
Pang
Gilead Sciences, Inc., Foster City, California.
Diana
D
Brainard
Christchurch Hospital and University of Otago, Christchurch, New Zealand.
Catherine A
CA
Stedman
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D012367:RNA, Viral / Q000187:drug effects*; D011897:Random Allocation; D012254:Ribavirin / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000235:genetics
D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
Clinical Trial Result; DAA; Direct-Acting Antiviral Agents; Drug