Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies

Autor: Fumitaka Suzuki, Hiromitsu Kumada, Go Fujimoto, Yoshiyasu Karino, Steve W. Ludmerer, Satoshi Mochida, Keisuke Nakamura, Anita Y. M. Howe, Niloufar Mobashery, Kazuaki Chayama
Rok vydání: 2016
Předmět:
0301 basic medicine
Cyclopropanes
Male
Indoles
Vaniprevir
Hepacivirus
Isoindoles
medicine.disease_cause
Gastroenterology
Polyethylene Glycols
chemistry.chemical_compound
0302 clinical medicine
Recurrence
Medicine
Sulfonamides
Middle Aged
Viral Load
Recombinant Proteins
Peginterferon alfa-2b
RNA
Viral
030211 gastroenterology & hepatology
Drug Therapy
Combination
Female
Viral load
medicine.drug
Adult
medicine.medical_specialty
Proline
Hepatitis C virus
Lactams
Macrocyclic
030106 microbiology
Alpha interferon
Interferon alpha-2
Antiviral Agents
Medication Adherence
03 medical and health sciences
Young Adult
Leucine
Internal medicine
Drug Resistance
Viral
Ribavirin
Humans
Adverse effect
Aged
Hepatitis
Hepatology
business.industry
Interferon-alpha
Hepatitis C
Chronic
medicine.disease
chemistry
business
Zdroj: Journal of gastroenterology and hepatology. 31(10)
ISSN: 1440-1746
Popis: Background and Aim Vaniprevir is a macrocyclic hepatitis C virus (HCV) non-structural (NS)3/4A protease inhibitor. The objective of these phase 3 multicenter, open-label trials was to evaluate the safety and efficacy of vaniprevir + peginterferon alfa-2b + ribavirin (PR) in Japanese patients with HCV genotype (GT)1 infection who had previously failed treatment with interferon-based regimens. Methods Japanese patients with chronic HCV GT1 were enrolled. In PN044, patients with previous relapse or virologic breakthrough were randomized to vaniprevir (300 mg twice daily) + PR for 12 weeks followed by PR for another 12 weeks (12-week arm) or vaniprevir + PR for 24 weeks (24-week arm). In PN045, patients with previous partial/null response received vaniprevir + PR for 24 weeks. The primary endpoint was sustained virologic response at 24 weeks after completing treatment (SVR24). Results In PN044 (n = 51), SVR24 was 92.0% and 96.2% in the 12- and 24-week arms, respectively. In PN045 (n = 42), SVR24 was 61.9% in all patients and 55.2% in previous null responders. In both studies, vaniprevir + PR was generally safe and well tolerated; the majority of adverse events were mild/moderate and included pyrexia, decreased hemoglobin, headache, nausea, pruritus, and decreased platelet count. Polymorphisms in the HCV NS3 gene at baseline (Y56, Q80, and V170) did not impact treatment outcome. Virologic failure was principally associated with the on-treatment emergence of R155 or D168 mutations. Conclusions Vaniprevir + PR is an effective, well-tolerated treatment for Japanese patients with HCV GT1 infection who failed previous interferon-based treatment. ClinicalTrials.gov Identifier NCT01405937 and NCT01405560 (Protocols PN044 and PN045). This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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