PMID- 32065330
OWN - NLM
STAT- MEDLINE
DCOM- 20211013
LR  - 20240328
IS  - 1435-5922 (Electronic)
IS  - 0944-1174 (Print)
IS  - 0944-1174 (Linking)
VI  - 55
IP  - 6
DP  - 2020 Jun
TI  - 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.
PG  - 640-652
LID - 10.1007/s00535-020-01672-0 [doi]
AB  - 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-naive 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.
FAU - Takehara, Tetsuo
AU  - Takehara T
AUID- ORCID: 0000-0001-5036-3457
AD  - Department of Gastroenterology and Hepatology, Osaka University Graduate School 
      of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan. 
      takehara@gh.med.osaka-u.ac.jp.
FAU - Chayama, Kazuaki
AU  - Chayama K
AD  - Department of Gastroenterology and Metabolism, Graduate School of Biomedical and 
      Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 
      734-8551, Japan.
FAU - Kurosaki, Masayuki
AU  - Kurosaki M
AD  - Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 
      1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
FAU - Yatsuhashi, Hiroshi
AU  - Yatsuhashi H
AD  - Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 
      Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
FAU - Tanaka, Yasuhito
AU  - Tanaka Y
AD  - Department of Virology and Liver Unit, Nagoya City University Graduate School of 
      Medical Sciences, Kawasumi, Mizuho, Nagoya, 467-8601, Japan.
FAU - Hiramatsu, Naoki
AU  - Hiramatsu N
AD  - Osaka Rosai Hospital, 1179-3 Kita, Sakai, Osaka, 591-8025, Japan.
FAU - Sakamoto, Naoya
AU  - Sakamoto N
AD  - Department of Gastroenterology and Hepatology, Faculty of Medicine and Graduate 
      School of Medicine, Hokkaido University, North 15 West 7 Kita-ku, Sapporo, 
      Hokkaido, 060-8638, Japan.
FAU - Asahina, Yasuhiro
AU  - Asahina Y
AD  - Department of Liver Disease Control, Department of Gastroenterology and 
      Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 
      Tokyo, 113-8519, Japan.
FAU - Nozaki, Akito
AU  - Nozaki A
AD  - Gastroenterological Center, Yokohama City University Medical Center, 4-57 
      Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.
FAU - Nakano, Toshikazu
AU  - Nakano T
AD  - Janssen Pharmaceutical K.K, 5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo, 
      101-0065, Japan.
FAU - Hagiwara, Yosuke
AU  - Hagiwara Y
AD  - Janssen Pharmaceutical K.K, 5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo, 
      101-0065, Japan.
FAU - Shimizu, Hiroko
AU  - Shimizu H
AD  - Clinical Pharmacology, Quantitative Sciences Division, R&D, Janssen 
      Pharmaceutical K.K., 5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo, 101-0065, 
      Japan.
FAU - Yoshida, Hiroki
AU  - Yoshida H
AD  - Clinical Biostatistics Group 1 Biostatistics Department, 5-2, Nishi-kanda 
      3-chome, Chiyoda-ku, Tokyo, 101-0065, Japan.
FAU - Huang, Yuhan
AU  - Huang Y
AD  - Statistics and Decision Sciences, Janssen (China) Research and Development, LLC., 
      6F, Building A, Xinyan Mansion, No. 65 Guiqing Road, Xuhui District, Shanghai, 
      People's Republic of China.
FAU - Biermer, Michael
AU  - Biermer M
AD  - Janssen Research and Development, Janssen Pharmaceutica NV, Turnhoutseweg 30, 
      2340, Beerse, Belgium.
FAU - Vijgen, Leen
AU  - Vijgen L
AD  - Janssen Research and Development, Janssen Pharmaceutica NV, Turnhoutseweg 30, 
      2340, Beerse, Belgium.
FAU - Hayashi, Norio
AU  - Hayashi N
AD  - Kansai Rosai Hospital, Inabasou 3-1-69, Amagasaki-shi, Hyogo, 660-8511, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200217
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Carbamates)
RN  - 0 (Drug Combinations)
RN  - 0 (Indoles)
RN  - 0 (Phosphoramides)
RN  - 9WS5RD66HZ (Simeprevir)
RN  - OF5P57N2ZX (Alanine)
RN  - OVR52K7BDW (odalasvir)
RN  - S83770Y75R (adafosbuvir)
RN  - WHI7HQ7H85 (Uridine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alanine/administration & dosage/analogs & derivatives
MH  - Antiviral Agents/*administration & dosage/adverse effects
MH  - Benzimidazoles/administration & dosage
MH  - Carbamates/administration & dosage
MH  - Drug Combinations
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - Hepacivirus/*genetics/isolation & purification
MH  - Hepatitis C, Chronic/*drug therapy/virology
MH  - Humans
MH  - Indoles/administration & dosage
MH  - Japan
MH  - Liver Cirrhosis/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Phosphoramides/administration & dosage
MH  - Simeprevir/administration & dosage
MH  - Sustained Virologic Response
MH  - Treatment Outcome
MH  - Uridine/administration & dosage/analogs & derivatives
PMC - PMC7242285
OTO - NOTNLM
OT  - AL-335
OT  - Hepatitis C virus
OT  - Japanese
OT  - Odalasvir
OT  - Simeprevir
COIS- Tetsuo Takehara has received an honorarium and a research grant from Janssen. 
      Kazuaki Chayama has received honoraria from AbbVie, Bristol-Myers Squibb, Chugoku 
      Electric Power, Dainippon Sumitomo, Eisai, Gilead Sciences, Mitsubishi Tanabe, 
      MSD, and Otsuka and research grants from AbbVie, Bristol-Myers Squibb, Chugoku 
      Electric Power, Daiichi Sankyo, Dainippon Sumitomo, EA Pharma, Eisai, Mochida 
      Pharmaceutical, MSD, Nippon Kayaku, Otsuka, Roche, Takeda, and Toray. Masayuki 
      Kurosaki, Naoki Hiramatsu, and Norio Hayashi have no conflicts of interest to 
      declare. Hiroshi Yatsuhashi has received a research grant from AbbVie. Yasuhito 
      Tanaka has received an honorarium from Gilead Sciences and research grants from 
      Chugai Pharmaceutical Co. Ltd., Gilead Sciences and Janssen. Naoya Sakamoto has 
      received honoraria from AbbVie, ASKA Pharmaceutical Co. Ltd., Asuka 
      Pharmaceutical Co. Ltd., Eisai, Gilead Sciences, MSD and Otsuka Pharmaceuticals, 
      and research grants from AbbVie, Chugai Pharmaceutical Co. Ltd., Gilead Sciences, 
      MSD, Otsuka Pharmaceuticals, Shonogi, and Takeda. Yasuhiro Asahina belongs to a 
      donation-funded department, funded by AbbVie GK, Chugai Pharmaceutical Co. Ltd., 
      Fujirebio Inc., Gilead Sciences, MSD, and Toray Industries Inc. Akito Nozaki has 
      received research grants from AbbVie GK and Gilead Sciences. Toshikazu Nakano, 
      Yosuke Hagiwara, Hiroko Shimizu, and Hiroki Yoshida are employees of Janssen 
      Pharmaceutical K.K. Yuhan Huang is an employee of Janssen (China) Research and 
      Development, LLC. Michael Biermer and Leen Vijgen are employees of Janssen 
      Pharmaceutica NV and shareholders of Johnson & Johnson.
EDAT- 2020/02/18 06:00
MHDA- 2021/10/14 06:00
PMCR- 2020/02/17
CRDT- 2020/02/18 06:00
PHST- 2019/06/11 00:00 [received]
PHST- 2020/01/18 00:00 [accepted]
PHST- 2020/02/18 06:00 [pubmed]
PHST- 2021/10/14 06:00 [medline]
PHST- 2020/02/18 06:00 [entrez]
PHST- 2020/02/17 00:00 [pmc-release]
AID - 10.1007/s00535-020-01672-0 [pii]
AID - 1672 [pii]
AID - 10.1007/s00535-020-01672-0 [doi]
PST - ppublish
SO  - J Gastroenterol. 2020 Jun;55(6):640-652. doi: 10.1007/s00535-020-01672-0. Epub 
      2020 Feb 17.