R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin.

R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa-2a +/- ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log(10) IU/mL. Synergy was observed between R1626 and peginterferon alfa-2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions.
A synergistic antiviral effect was observed when R1626 was combined with peginterferon alfa-2a +/- ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with peginterferon alfa-2a and ribavirin is underway.
AuthorsPaul J Pockros, David Nelson, Eliot Godofsky, Maribel Rodriguez-Torres, Gregory T Everson, Michael W Fried, Reem Ghalib, Stephen Harrison, Lisa Nyberg, Mitchell L Shiffman, Isabel Najera, Anna Chan, George Hill
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 48 Issue 2 Pg. 385-97 (Aug 2008) ISSN: 1527-3350 [Electronic] United States
PMID18570306 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
Chemical References
  • 4'-azidocytidine
  • Antiviral Agents
  • Interferon-alpha
  • Nucleosides
  • Prodrugs
  • RNA, Viral
  • Recombinant Proteins
  • peginterferon alfa-2a
  • Polyethylene Glycols
  • Ribavirin
  • Cytidine
  • interferon alfa-2a
  • Alanine Transaminase
  • balapiravir
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase (blood)
  • Antiviral Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
  • Cytidine (analogs & derivatives, blood)
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Resistance, Viral
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Hepacivirus (enzymology, genetics)
  • Humans
  • Interferon-alpha (adverse effects, therapeutic use)
  • Male
  • Middle Aged
  • Neutropenia (chemically induced)
  • Nucleosides (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
  • Polyethylene Glycols (adverse effects, therapeutic use)
  • Prodrugs (administration & dosage, adverse effects, metabolism, pharmacokinetics, therapeutic use)
  • RNA, Viral (antagonists & inhibitors, blood)
  • Recombinant Proteins
  • Ribavirin (adverse effects, therapeutic use)
  • Treatment Outcome
  • Viral Load

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: