Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.

In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.
We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea.
Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).
AuthorsNezam Afdhal, Stefan Zeuzem, Paul Kwo, Mario Chojkier, Norman Gitlin, Massimo Puoti, Manuel Romero-Gomez, Jean-Pierre Zarski, Kosh Agarwal, Peter Buggisch, Graham R Foster, Norbert Bräu, Maria Buti, Ira M Jacobson, G Mani Subramanian, Xiao Ding, Hongmei Mo, Jenny C Yang, Phillip S Pang, William T Symonds, John G McHutchison, Andrew J Muir, Alessandra Mangia, Patrick Marcellin,
JournalThe New England journal of medicine (N Engl J Med) Vol. 370 Issue 20 Pg. 1889-98 (May 15 2014) ISSN: 1533-4406 [Electronic] United States
PMID24725239 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • RNA, Viral
  • ledipasvir
  • Ribavirin
  • Uridine Monophosphate
  • Sofosbuvir
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents (adverse effects, therapeutic use)
  • Benzimidazoles (adverse effects, therapeutic use)
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Fluorenes (adverse effects, therapeutic use)
  • Genotype
  • Hepacivirus (genetics)
  • Hepatitis C, Chronic (drug therapy, virology)
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral (blood)
  • Ribavirin (adverse effects, therapeutic use)
  • Sofosbuvir
  • Uridine Monophosphate (adverse effects, analogs & derivatives, therapeutic use)
  • Viral Load
  • Young Adult

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