Efficacy of Ledipasvir and Sofosbuvir, With or Without Ribavirin, for 12 Weeks in Patients With HCV Genotype 3 or 6 Infection

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 149; no. 6; pp. 1454 - 1461.e1
• Main Authors: Gane, Edward J., Hyland, Robert H., An, Di, Svarovskaia, Evguenia, Pang, Phillip S., Brainard, Diana, Stedman, Catherine A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015
• Subjects: Adult; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Benzimidazoles - administration & dosage; Benzimidazoles - therapeutic use; Clinical Trial Result; DAA; Direct-Acting Antiviral Agents; Drug; Drug Therapy, Combination - methods; Female; Fluorenes - administration & dosage; Fluorenes - therapeutic use; Gastroenterology and Hepatology; Genotype; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - pathogenicity; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Male; Middle Aged; New Zealand; Random Allocation; Ribavirin - administration & dosage; Ribavirin - classification; Ribavirin - therapeutic use; RNA, Viral - drug effects; Sofosbuvir - administration & dosage; Sofosbuvir - therapeutic use; Time Factors; Treatment Outcome; Viral Load - drug effects; Viral Load - genetics; New Zealand; Drug; LLOQ; FDA; Direct-Acting Antiviral Agents; FDC; DAA; Clinical Trial Result; CI; EC50; HCV; SVR; BMI; body mass index; 50% effective concentration; fixed-dose combination; EC 50; hepatitis C virus; confidence interval; US Food and Drug Administration; lower limit of quantification; sustained virologic response
• DOI: 10.1053/j.gastro.2015.07.063
• ISSN: 0016-5085; 1528-0012

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. 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]). 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. 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.