Twelve-week ravidasvir plus ritonavir-boosted danoprevir and ribavirin for non-cirrhotic HCV genotype 1 patients: A phase 2 study.

Abstract

BACKGROUND AND AIM:

The need for all-oral hepatitis C virus (HCV) treatments with higher response rates, improved tolerability, and lower pill burden compared with interferon-inclusive regimen has led to the development of new direct-acting antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment-naïve Asian HCV genotype 1 (GT1) patients without cirrhosis.

METHODS:

A total of 38 treatment-naïve, non-cirrhotic adult HCV GT1 patients were enrolled in this multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight < 75/≥ 75 kg) for 12 weeks. The primary endpoint was the rate of sustained virologic response 12 weeks after the end of treatment (SVR12).

RESULTS:

Of 38 patients, all (100%) achieved SVR12. During the study, no treatment-related serious adverse events, no patients discontinued treatment due to adverse events, and no deaths were reported. Six of 37 (16%) patients with available sequences had HCV NS5A resistance-associated variants at baseline. All patients (6/6) with baseline NS5A resistance-associated variants achieved SVR12.

CONCLUSIONS:

Twelve-week RDV and DNVr in combination with RBV for 12 weeks achieves the SVR12 rate of 100% in treatment-naïve non-cirrhotic Asian patients with HCV GT1 infection. This interferon-free regimen is also safe and well tolerated.

• Authors: Jia-Horng Kao, Min-Lung Yu, Chi-Yi Chen, Cheng-Yuan Peng, Ming-Yao Chen, Huoling Tang, Qiaoqiao Chen, Jinzi J Wu
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 33 Issue 8 Pg. 1507-1510 (Aug 2018) ISSN: 1440-1746 [Electronic] Australia
• PMID: 29346834 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Antiviral Agents
• Cyclopropanes
• Isoindoles
• Lactams
• Lactams, Macrocyclic
• Sulfonamides
• Ribavirin
• danoprevir
• Proline
• Ritonavir

Topics

• Administration, Ophthalmic
• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents
• Asian People
• Cyclopropanes
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Isoindoles
• Lactams (administration & dosage)
• Lactams, Macrocyclic
• Liver Cirrhosis
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Ribavirin (administration & dosage)
• Ritonavir (administration & dosage)
• Sulfonamides (administration & dosage)
• Time Factors
• Treatment Outcome