Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection
Copyright © 2022 Massachusetts Medical Society..
BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins.
METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication.
RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4).
CONCLUSIONS: In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.).
Errataetall: |
CommentIn: N Engl J Med. 2022 Nov 24;387(21):1996-1998. - PMID 36346068 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:387 |
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Enthalten in: |
The New England journal of medicine - 387(2022), 21 vom: 24. Nov., Seite 1957-1968 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Yuen, Man-Fung [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 29.11.2022 Date Revised 22.03.2023 published: Print-Electronic ClinicalTrials.gov: NCT04449029 CommentIn: N Engl J Med. 2022 Nov 24;387(21):1996-1998. - PMID 36346068 Citation Status MEDLINE |
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doi: |
10.1056/NEJMoa2210027 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM348598440 |
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500 | |a published: Print-Electronic | ||
500 | |a ClinicalTrials.gov: NCT04449029 | ||
500 | |a CommentIn: N Engl J Med. 2022 Nov 24;387(21):1996-1998. - PMID 36346068 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2022 Massachusetts Medical Society. | ||
520 | |a BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins | ||
520 | |a METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication | ||
520 | |a RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4) | ||
520 | |a CONCLUSIONS: In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.) | ||
650 | 4 | |a Clinical Trial, Phase II | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Randomized Controlled Trial | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Antiviral Agents |2 NLM | |
650 | 7 | |a DNA, Viral |2 NLM | |
650 | 7 | |a Hepatitis B e Antigens |2 NLM | |
650 | 7 | |a Hepatitis B Surface Antigens |2 NLM | |
650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
650 | 7 | |a RNA, Viral |2 NLM | |
650 | 7 | |a RNA, Messenger |2 NLM | |
700 | 1 | |a Lim, Seng-Gee |e verfasserin |4 aut | |
700 | 1 | |a Plesniak, Robert |e verfasserin |4 aut | |
700 | 1 | |a Tsuji, Keiji |e verfasserin |4 aut | |
700 | 1 | |a Janssen, Harry L A |e verfasserin |4 aut | |
700 | 1 | |a Pojoga, Cristina |e verfasserin |4 aut | |
700 | 1 | |a Gadano, Adrian |e verfasserin |4 aut | |
700 | 1 | |a Popescu, Corneliu P |e verfasserin |4 aut | |
700 | 1 | |a Stepanova, Tatyana |e verfasserin |4 aut | |
700 | 1 | |a Asselah, Tarik |e verfasserin |4 aut | |
700 | 1 | |a Diaconescu, Gheorghe |e verfasserin |4 aut | |
700 | 1 | |a Yim, Hyung Joon |e verfasserin |4 aut | |
700 | 1 | |a Heo, Jeong |e verfasserin |4 aut | |
700 | 1 | |a Janczewska, Ewa |e verfasserin |4 aut | |
700 | 1 | |a Wong, Alexander |e verfasserin |4 aut | |
700 | 1 | |a Idriz, Nevin |e verfasserin |4 aut | |
700 | 1 | |a Imamura, Michio |e verfasserin |4 aut | |
700 | 1 | |a Rizzardini, Giuliano |e verfasserin |4 aut | |
700 | 1 | |a Takaguchi, Koichi |e verfasserin |4 aut | |
700 | 1 | |a Andreone, Pietro |e verfasserin |4 aut | |
700 | 1 | |a Arbune, Manuela |e verfasserin |4 aut | |
700 | 1 | |a Hou, Jinlin |e verfasserin |4 aut | |
700 | 1 | |a Park, Sung Jae |e verfasserin |4 aut | |
700 | 1 | |a Vata, Andrei |e verfasserin |4 aut | |
700 | 1 | |a Cremer, Jennifer |e verfasserin |4 aut | |
700 | 1 | |a Elston, Robert |e verfasserin |4 aut | |
700 | 1 | |a Lukić, Tamara |e verfasserin |4 aut | |
700 | 1 | |a Quinn, Geoff |e verfasserin |4 aut | |
700 | 1 | |a Maynard, Lauren |e verfasserin |4 aut | |
700 | 1 | |a Kendrick, Stuart |e verfasserin |4 aut | |
700 | 1 | |a Plein, Helene |e verfasserin |4 aut | |
700 | 1 | |a Campbell, Fiona |e verfasserin |4 aut | |
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700 | 0 | |a B-Clear Study Group |e verfasserin |4 aut | |
700 | 1 | |a Colombato, Luis |e investigator |4 oth | |
700 | 1 | |a Gadano, Adrian |e investigator |4 oth | |
700 | 1 | |a Genov, Jordan |e investigator |4 oth | |
700 | 1 | |a Pavlov, Dimitar |e investigator |4 oth | |
700 | 1 | |a Petrova, Diana |e investigator |4 oth | |
700 | 1 | |a Tchernev, Konstantin |e investigator |4 oth | |
700 | 1 | |a Coffin, Carla |e investigator |4 oth | |
700 | 1 | |a Ghesquiere, Wayne |e investigator |4 oth | |
700 | 1 | |a Janssen, Harry |e investigator |4 oth | |
700 | 1 | |a Marotta, Paul |e investigator |4 oth | |
700 | 1 | |a Poulin, Sebastien |e investigator |4 oth | |
700 | 1 | |a Vachon, Marie-Louise |e investigator |4 oth | |
700 | 1 | |a Wong, Alexander |e investigator |4 oth | |
700 | 1 | |a Dou, Xiaoguang |e investigator |4 oth | |
700 | 1 | |a Hou, Jinlin |e investigator |4 oth | |
700 | 1 | |a Jia, Jidong |e investigator |4 oth | |
700 | 1 | |a Ning, Qin |e investigator |4 oth | |
700 | 1 | |a Ren, Hong |e investigator |4 oth | |
700 | 1 | |a Wang, Guiqiang |e investigator |4 oth | |
700 | 1 | |a Xie, Qing |e investigator |4 oth | |
700 | 1 | |a Xie, Wen |e investigator |4 oth | |
700 | 1 | |a Asselah, Tarik |e investigator |4 oth | |
700 | 1 | |a Leroy, Vincent |e investigator |4 oth | |
700 | 1 | |a Loustaud-Ratti, Véronique |e investigator |4 oth | |
700 | 1 | |a Serfaty, Lawrence |e investigator |4 oth | |
700 | 1 | |a Tran, Albert |e investigator |4 oth | |
700 | 1 | |a Zoulim, Fabien |e investigator |4 oth | |
700 | 1 | |a Hartikainen, Jukka |e investigator |4 oth | |
700 | 1 | |a Kremer, Andreas |e investigator |4 oth | |
700 | 1 | |a Lutz, Thomas |e investigator |4 oth | |
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700 | 1 | |a Atsukawa, Masanori |e investigator |4 oth | |
700 | 1 | |a Fujiyama, Shigetoshi |e investigator |4 oth | |
700 | 1 | |a Imamura, Michio |e investigator |4 oth | |
700 | 1 | |a Inoue, Jun |e investigator |4 oth | |
700 | 1 | |a Joko, Kouji |e investigator |4 oth | |
700 | 1 | |a Kakinoki, Kaheita |e investigator |4 oth | |
700 | 1 | |a Komori, Atsumasa |e investigator |4 oth | |
700 | 1 | |a Komura, Takuya |e investigator |4 oth | |
700 | 1 | |a Kurosaki, Masayuki |e investigator |4 oth | |
700 | 1 | |a Takaguchi, Koichi |e investigator |4 oth | |
700 | 1 | |a Takehara, Tetsuo |e investigator |4 oth | |
700 | 1 | |a Tanaka, Yasuhito |e investigator |4 oth | |
700 | 1 | |a Tsuji, Keiji |e investigator |4 oth | |
700 | 1 | |a Md Salleh, Muhammad Firdaus |e investigator |4 oth | |
700 | 1 | |a Mohamed, Rosmawati |e investigator |4 oth | |
700 | 1 | |a Domingo, Felix |c Jr |e investigator |4 oth | |
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700 | 1 | |a Tomasiewicz, Krzysztof |e investigator |4 oth | |
700 | 1 | |a Heo, Jeong |e investigator |4 oth | |
700 | 1 | |a Kim, Hyung Joon |e investigator |4 oth | |
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700 | 1 | |a Diaconescu, Gheorghe |e investigator |4 oth | |
700 | 1 | |a Marincu, Iosif |e investigator |4 oth | |
700 | 1 | |a Moraru, Adrian |e investigator |4 oth | |
700 | 1 | |a Pojoga, Cristina |e investigator |4 oth | |
700 | 1 | |a Popescu, Corneliu |e investigator |4 oth | |
700 | 1 | |a Vata, Andrei |e investigator |4 oth | |
700 | 1 | |a Bogomolov, Pavel |e investigator |4 oth | |
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700 | 1 | |a Gusev, Denis |e investigator |4 oth | |
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700 | 1 | |a Moosa, Naeem |e investigator |4 oth | |
700 | 1 | |a Punt, Zelda |e investigator |4 oth | |
700 | 1 | |a Wilhase, Agatha |e investigator |4 oth | |
700 | 1 | |a Xaba, Sabelo |e investigator |4 oth | |
700 | 1 | |a Ampuero Herrojo, Javier |e investigator |4 oth | |
700 | 1 | |a Andrade Bellido, Raul |e investigator |4 oth | |
700 | 1 | |a Buti, Maria |e investigator |4 oth | |
700 | 1 | |a Calleja Panero, José Luís |e investigator |4 oth | |
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