Interferon-free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study.

Abstract

BACKGROUND & AIMS:

Setrobuvir is a direct-acting antiviral (DAA) non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study examined interferon-free combinations containing setrobuvir, a ritonavir-boosted protease inhibitor (danoprevir/r) and ribavirin, with/without the nucleoside inhibitor mericitabine in HCV genotype (G)1 patients.

METHODS:

Non-cirrhotic treatment-naïve patients (N = 110) were randomized to five groups. Three groups received a 14-day mericitabine/ribavirin lead-in followed by treatment with 3 DAAs (setrobuvir, danoprevir/r, mericitabine) plus ribavirin for 12 weeks (Group A: G1a; D: G1b) or 24 weeks (B: G1a), and two groups received 2 DAAs (setrobuvir, danoprevir/r) plus ribavirin for 12 weeks (E: G1b) or 24 weeks (C: G1a). Efficacy was defined as sustained virological response (HCV RNA <25 IU/ml after 12 weeks' follow-up, SVR12).

RESULTS:

Two groups met predefined futility criteria for breakthrough (C) or relapse (A) and were discontinued. SVR12 rates were 42.9% (3/7) and 74.1% (20/27) in G1a patients in Groups A and B, respectively, and 95.7% (22/23) and 68.2% (15/22) in G1b patients in Groups D and E respectively. All G1a patients assigned to 24 weeks of treatment who experienced a decrease in HCV RNA of ≥2.3 log10 IU by the end of the lead-in period (n = 28) achieved SVR12. Overall, treatment was well tolerated and most adverse events were mild to moderate. No major safety signals were identified.

CONCLUSIONS:

An interferon-free setrobuvir-based regimen (3 DAAs plus ribavirin) is safe and effective in treatment-naïve G1 patients.

• Authors: Donald M Jensen, Michael Brunda, Robert Elston, Edward J Gane, Jacob George, Katerina Glavini, Janet M Hammond, Sophie Le Pogam, Isabel Nájera, Sharon Passe, Anna Piekarska, Ignacio Rodriguez, Stefan Zeuzem, Tom Chu, ANNAPURNA study investigators
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 36 Issue 4 Pg. 505-14 (Apr 2016) ISSN: 1478-3231 [Electronic] United States
• PMID: 26519669 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• 2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine
• Antiviral Agents
• Benzothiadiazines
• Cyclopropanes
• Isoindoles
• Lactams
• Lactams, Macrocyclic
• Quinolones
• RNA, Viral
• Sulfonamides
• Deoxycytidine
• Ribavirin
• Interferons
• danoprevir
• Proline
• setrobuvir

Topics

• Adult
• Antiviral Agents (adverse effects, therapeutic use)
• Australia
• Benzothiadiazines (adverse effects, therapeutic use)
• Cyclopropanes
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Drug Therapy, Combination
• Europe
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (diagnosis, drug therapy)
• Humans
• Interferons (adverse effects, therapeutic use)
• Isoindoles
• Lactams (therapeutic use)
• Lactams, Macrocyclic
• Male
• Middle Aged
• New Zealand
• Phenotype
• Proline (analogs & derivatives)
• Quinolones (adverse effects, therapeutic use)
• RNA, Viral (blood)
• Remission Induction
• Ribavirin (therapeutic use)
• Sulfonamides (therapeutic use)
• Time Factors
• Treatment Outcome
• United States
• Viral Load