한빛사논문
- 조회102
Maria Buti 1∗, Jeong Heo 2,3∗, Yasuhito Tanaka 4, Pietro Andreone 5,6, Masanori Atsukawa 7, Joaquín Cabezas 8,9, Eric Chak 10, Carla S. Coffin 11, Kei Fujiwara 12, Natalya Gankina 13, Stuart C. Gordon 14, Ewa Janczewska 15, Atsumasa Komori 16, Pietro Lampertico 17,18, Stuart McPherson 19, Vyacheslav Morozov 20, Robert Plesniak 21, Sébastien Poulin 22, Pablo Ryan 23, Olga Sagalova 24, Guoping Sheng 25, Natalya Voloshina 26, Qing Xie 27, Hyung Joon Yim 28, Susan Dixon 29, Melanie Paff 30, Leigh Felton 29, Maximilian Lee 30, Thomas Greene 30, Jessica Lim 30, Divya Lakshminarayanan 30, Grant McGonagle 29, Helene Plein 29, Amir Youssef 30, Rob Elston 31, Stuart Kendrick 31, Dickens Theodore 32
1Liver Unit, Hospital Vall d'Hebrón, Barcelona and CIBER-EHD del Instituto Carlos III, Barcelona, Spain
2Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Republic of Korea
3Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
4Department of Gastroenterology and Hepatology, Kumamoto University Hospital, Kumamoto, Japan
5Medicina Interna a indirizzo Metabolico-Nutrizionale, Ospedale Clinicizzato di Baggiovara, AOU di Modena, Modena, Italy
6Dipartimento SMECHIMAI, Università di Modena e Reggio Emilia, Modena, Italy
7Nippon Medical School Hospital, Tokyo, Japan
8Gastroenterology and Hepatology Department, University Hospital Marques de Valdecilla, Santander, Spain
9Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Santander, Spain
10UC Davis, Sacramento, California, USA
11Department of Medicine, Cumming School of Medicine, University of Calgary, Alberta, Calgary, Canada
12Nagoya City University Hospital, Aichi, Japan
13Krasnojarsk Regional Center of AIDS prevention, Krasnojarsk, Russian Federation
14Henry Ford Health and Wayne State University School of Medicine, Detroit, MI, USA
15Department of Basic Medical Sciences, Faculty of Public Health in Bytom, Medical University of Silesia, Myslowice, Poland
16National Hospital Organization, NHO Nagasaki Medical Center, Nagasaki, Japan
17Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
18CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
19Hepatology and Newcastle NIHR Biomedical Research Centre, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle-upon-Tyne, UK
20Hepatologist Medical Company, Samara, Russian Federation
21University of Rzeszow Centrum Medyczne w Lancucie Sp. z o.o., Lancut, Poland
22Clinique médecine Urbaine du Quartier Latin, Montréal, Québec, Canada
23Hospital Infanta Leonor and CIBERINFEC, del Instituto Carlos III., Madrid, Spain
24South Ural State Medical University, Chelyabinsk, Russian Federation
25Department of Infectious Disease, Shulan (Hangzhou) Hospital affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, Zhejiang, China
26Medical Centre Healthy Family, Novosibirsk, Russian Federation
27Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
28Korea University Ansan Hospital, Ansan, Republic of Korea
29GSK, London, UK
30GSK, Collegeville, PA, USA
31GSK, Stevenage, UK
32GSK, Durham, NC, USA
∗Author names in bold designate shared co-first authorship
Corresponding authors: Maria Buti, Jeong Heo
Abstract
Background & aims: Bepirovirsen, an antisense oligonucleotide, induces sustained hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA below lower limit of quantification (<LLOQ) in a subset of patients. The B-Together study investigated if sequential bepirovirsen and pegylated interferon-α-2a (Peg-IFN) therapy can reduce relapse and improve response rates.
Methods: Phase 2b, multicentre, randomised, open-label trial. Participants on stable nucleos(t)ide analog (NA) therapy were randomised 1:1 to bepirovirsen 300 mg once weekly (plus loading dose on Days 4 and 11) for 24 (Arm 1) or 12 (Arm 2) weeks followed by Peg-IFN 180 mcg once weekly for up to 24 weeks, with up to 36 weeks follow-up. Participants continued NA therapy throughout.
Primary outcome: proportion of participants with HBsAg <0.05 IU/mL and HBV DNA <LLOQ for 24 weeks after planned end of Peg-IFN treatment, in the absence of newly initiated antiviral therapy.
Results: The intent-to-treat population included 108 participants (Arm 1=55; Arm 2=53). The primary outcome was achieved by 5 (9%) participants in Arm 1 and 8 (15%) in Arm 2. All responders had baseline HBsAg ≤3000 IU/mL. Indirect comparison with the Phase 2b study B-Clear indicates that sequential addition of Peg-IFN may reduce the relapse rates previously observed with bepirovirsen alone. The proportions of participants with adverse events (AEs) and treatment-related AEs in both treatment windows were similar between treatment arms.
Conclusions: Sequential therapy with bepirovirsen followed by Peg-IFN is tolerable and effective in participants with chronic HBV infection on stable NA. This proof-of-concept trial demonstrates a potential strategy to extend responses to bepirovirsen by reducing relapse.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-09-02)
- 국내(교신)+국외 연구진
- 의약학 > 감염의학
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