Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naïve hepatitis C genotype 1-infected patients in Japan: the DRAGON study.

Abstract

BACKGROUND:

Efficacy, safety and pharmacokinetics of simeprevir (TMC435), a once-daily, noncovalent, oral hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in combination with peginterferon α-2a/ribavirin (PegIFNα-2a/RBV) for treatment-naïve, HCV genotype 1-infected patients in Japan.

METHODS:

In a multicenter, randomized clinical trial in Japan, ninety-two patients received either simeprevir (50 or 100 mg QD) for 12 or 24 weeks with PegIFNα-2a/RBV for 24 or 48 weeks (according to response-guided therapy [RGT] criteria), or PegIFNα-2a/RBV for 48 weeks (PR48 group).

RESULTS:

Compared with the PR48 group, plasma HCV RNA reductions in the simeprevir groups were rapid and more substantial (Week 4: -5.2, -5.2 and -2.9 log10IU/mL for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively). High rapid virologic response rates (83, 90, and 8 % for simeprevir 50 mg combined, 100 mg combined, and PR48 groups, respectively) led to high sustained virologic response rates (77-92 %, compared with 46 % for PR48). All but one of the simeprevir-treated patients were eligible to complete treatment after 24 weeks (RGT). Relapse rates in simeprevir-treated patients were low (8-17 %, compared with 36 % for the PR48 group). There were no notable differences in the safety profile between the simeprevir and PR48 groups.

CONCLUSIONS:

The addition of simeprevir QD to PegIFNα-2a/RBV, as compared with PegIFNα-2a/RBV alone, demonstrated potent antiviral activity and significantly improved the rates of sustained virologic response, with a shortened 24-week treatment duration, in treatment-naive patients infected with HCV genotype 1 in Japan. Simeprevir was generally safe and well tolerated. (ClinicalTrials.gov number, NCT00996476).

• Authors: Norio Hayashi, Chiharu Seto, Mai Kato, Yuji Komada, Shoichiro Goto
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 49 Issue 1 Pg. 138-47 (Jan 2014) ISSN: 1435-5922 [Electronic] Japan
• PMID: 24005956 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Heterocyclic Compounds, 3-Ring
• Interferon-alpha
• RNA, Viral
• Recombinant Proteins
• Sulfonamides
• Polyethylene Glycols
• Ribavirin
• Simeprevir
• peginterferon alfa-2a

Topics

• Administration, Oral
• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Hepacivirus (isolation & purification)
• Hepatitis C, Chronic (drug therapy, virology)
• Heterocyclic Compounds, 3-Ring (administration & dosage, adverse effects, therapeutic use)
• Humans
• Interferon-alpha (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, adverse effects, therapeutic use)
• RNA, Viral (blood)
• Recombinant Proteins (administration & dosage, adverse effects, therapeutic use)
• Recurrence
• Ribavirin (administration & dosage, adverse effects, therapeutic use)
• Simeprevir
• Sulfonamides (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Viral Load
• Young Adult