JNJ-4178 (adafosbuvir, odalasvir, and simeprevir) in Japanese patients with chronic hepatitis C virus genotype 1 or 2 infection with or without compensated cirrhosis: the Phase IIa OMEGA-3 study.

Abstract

BACKGROUND:

The efficacy, safety, and pharmacokinetics of the combination of three direct-acting antiviral (DAA) agents (adafosbuvir [also known as AL-335], odalasvir, and simeprevir) were investigated in DAA treatment-naïve Japanese patients with genotype (GT)1 or GT2 chronic hepatitis C virus (HCV) infection, with or without compensated cirrhosis.

METHODS:

In this Phase IIa, open-label, multicenter study-OMEGA-3 (NCT02993250)-patients received JNJ-4178 (adafosbuvir 800 mg once daily [QD], odalasvir 25 mg QD, and simeprevir 75 mg QD) for 8 (non-cirrhotic patients; Cohort 1) or 12 (cirrhotic patients; Cohort 2) weeks. Patients were followed-up to 24 weeks following the end of treatment (EOT). The primary endpoint was safety, including adverse events (AEs).

RESULTS:

Overall, 33 patients were enrolled into Cohort 1 (N = 22) or 2 (N = 11) and received combined treatment with JNJ-4178. During the treatment and follow-up phases, a higher percentage of patients in Cohort 2 (81.8%) experienced AEs compared with Cohort 1 (68.2%), but the incidence of treatment-related AEs was similar. Most AEs were mild-to-moderate in severity and no patients discontinued due to an AE. There was one serious AE (cataract) in a patient in Cohort 2, which was not considered related to treatment. All patients achieved sustained virologic response 12 weeks after EOT (SVR12). No incidences of viral relapse were observed during follow-up.

CONCLUSIONS:

In HCV GT1- and GT2-infected Japanese patients, treatment with JNJ-4178 was well tolerated and resulted in 100% of patients achieving SVR12.

• Authors: Tetsuo Takehara, Kazuaki Chayama, Masayuki Kurosaki, Hiroshi Yatsuhashi, Yasuhito Tanaka, Naoki Hiramatsu, Naoya Sakamoto, Yasuhiro Asahina, Akito Nozaki, Toshikazu Nakano, Yosuke Hagiwara, Hiroko Shimizu, Hiroki Yoshida, Yuhan Huang, Michael Biermer, Leen Vijgen, Norio Hayashi
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 55 Issue 6 Pg. 640-652 (Jun 2020) ISSN: 1435-5922 [Electronic] Japan
• PMID: 32065330 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antiviral Agents
• Benzimidazoles
• Carbamates
• Drug Combinations
• Indoles
• Phosphoramides
• Simeprevir
• Alanine
• odalasvir
• adafosbuvir
• Uridine

Topics

• Adult
• Aged
• Alanine (administration & dosage, analogs & derivatives)
• Antiviral Agents (administration & dosage, adverse effects)
• Benzimidazoles (administration & dosage)
• Carbamates (administration & dosage)
• Drug Combinations
• Female
• Follow-Up Studies
• Genotype
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Indoles (administration & dosage)
• Japan
• Liver Cirrhosis (drug therapy)
• Male
• Middle Aged
• Phosphoramides (administration & dosage)
• Simeprevir (administration & dosage)
• Sustained Virologic Response
• Treatment Outcome
• Uridine (administration & dosage, analogs & derivatives)