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A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus

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Abstract

Background

The standard-of-care regimen for chronic hepatitis C virus (HCV) infection in Korea, pegylated-interferon-alpha plus ribavirin, is poorly tolerated. Ledipasvir/sofosbuvir is a two-drug, fixed-dose combination tablet approved in the USA, European Union, and Japan for chronic genotype 1 HCV infection.

Methods

This single-arm, phase IIIb study (NCT02021656) investigated the efficacy and safety of ledipasvir/sofosbuvir fixed-dose combination tablet for 12 weeks in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 HCV with or without compensated cirrhosis.

Results

The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 99 % (92/93), with rates of 100 % (46/46) and 98 % (46/47) in treatment-naïve and treatment-experienced patients, respectively. There were no on-treatment failures. One patient relapsed after the end of treatment. The most common treatment-emergent adverse events were headache (8 %, 7/93) and fatigue (6 %, 6/93). There were no grade 3 or 4 adverse events, seven grade 3 laboratory abnormalities, and one premature discontinuation of study treatment (due to nonserious mouth ulceration). None of the three reported serious adverse events were related to treatment.

Conclusions

These data suggest that 12 weeks of ledipasvir/sofosbuvir is effective and well tolerated in treatment-naïve and treatment-experienced Korean patients with chronic genotype 1 HCV infection.

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Acknowledgements

This study was funded in full by Gilead Sciences, Inc. The writing and preparation of this paper were funded by Gilead Sciences, Inc. The initial data analyses were undertaken by the listed authors. Writing support was provided by Tiffany DeSimone, PhD, of BlueMomentum, an Ashfield Company, part of UDG Healthcare plc, and funded by Gilead Sciences, Inc.

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    Authors and Affiliations

    1. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

      Young-Suk Lim

    2. Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

      Sang Hoon Ahn & Kwang-Hyub Han

    3. Department of Gastroenterology and Hepatology, Gangnam Severance Hospital, Yonsei University Health System, Seoul, South Korea

      Kwan Sik Lee

    4. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

      Seung Woon Paik

    5. Department of Infectious Diseases, Gastroenterology, and Hepatology, Inje University, Pusan Paik Hospital, Busan, South Korea

      Youn-Jae Lee

    6. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea

      Sook-Hyang Jeong

    7. Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea

      Ju-Hyun Kim

    8. Department of Gastroenterology, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, South Korea

      Seung Kew Yoon

    9. Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, South Korea

      Hyung Joon Yim

    10. Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea

      Won Young Tak

    11. Department of Internal Medicine, Dong-A University Medical Center, Busan, South Korea

      Sang-Young Han

    12. Gilead Sciences, Inc, Foster City, CA, USA

      Jenny C. Yang, Hongmei Mo, Kimberly L. Garrison, Bing Gao, Steven J. Knox & Phillip S. Pang

    13. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine and Liver Research Institute, Seoul, South Korea

      Yoon Jun Kim

    14. Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea

      Kwan-Soo Byun

    15. Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea

      Young Seok Kim

    16. Department of Internal Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, South Korea

      Jeong Heo

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    Correspondence to Kwang-Hyub Han.

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    Conflict of interest

    Young-Suk Lim has served as an advisor for Bayer Healthcare, Bristol-Myers Squibb, and Gilead Sciences, and has received research funding from Bayer Healthcare, Bristol-Myers Squibb, Gilead Sciences, and Novartis. Sang Hoon Ahn has served as an advisor and lecturer for Bristol-Myers Squibb, Gilead Sciences, F. Hoffmann-La Roche, Merck, Janssen, AbbVie, Novartis, Boeringher Ingelheim, and AVIVAX, and has received unrestricted grants from Bristol-Myers Squibb, Gilead Sciences, and F. Hoffmann-La Roche for investigator-initiated trials. Seung Woon Paik has received research funding from Bristol-Myers Squibb, Gilead Sciences, F. Hoffmann-La Roche, Merck, Janssen, and AbbVie. Hyung Joon Yim has received research funds from Handok Pharmacuetical Company and Gilead Sciences. Yoon Jun Kim has served as a speaker and advisory board member for Gilead Sciences, Bayer Healthcare, AbbVie, Novartis, and F. Hoffman-La Roche and has also received research funding from Gilead Sciences, Bristol-Myers Squibb, and F. Hoffman-La Roche. Kwan-Soo Byun has served as an advisory board member for Gilead Sciences and has received research funding from Gilead Sciences, Bristol-Myers Squibb, and Medigen Biotechnology Corporation. Jenny C. Yang, Hongmei Mo, Kimberly L. Garrison, Bing Gao, Steven J. Knox, and Phillip S. Pang are employees of and own stocks and shares in Gilead Sciences, Inc. Kwan Sik Lee, Youn-Jae Lee, Sook-Hyang Jeong, Ju-Hyun Kim, Seung Kew Yoon, Won Young Tak, Sang-Young Han, Young Seok Kim, Jeong Heo, and Kwang-Hyub Han have nothing to declare.

    Studies with human subjects

    All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Written informed consent was obtained from all patients included in the study. The protocol was approved by the ethics committees/institutional review boards of participating centers and conformed to Good Clinical Practice guidelines and Declaration of Helsinki principles. This article does not contain any studies with animal subjects.

    Additional information

    Y.-S. Lim, S.H. Ahn contributed equally to this work.

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    Lim, YS., Ahn, S.H., Lee, K.S. et al. A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus. Hepatol Int 10, 947–955 (2016). https://doi.org/10.1007/s12072-016-9726-5

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