Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy

Yuen, Man‐Fung; Heo, Jeong; Kumada, Hiromitsu; Suzuki, Fumitaka; Suzuki, Yoshiyuki; Xie, Qing; Jia, Jidong; Karino, Yoshiyasu; Hou, Jinlin; Chayama, Kazuaki; Imamura, Michio; Lao-Tan, Judy; Lim, Seng Gee; Tanaka, Yasuhito; Xie, Wen; Yoon, Jeesun; Duan, Zhongping; Kurosaki, Masayuki; Park, Sungjae; Labio, Madalinee Eternity; Kumar, Rajneesh; Kweon, Young-Oh; Yim, Hyung Joon; Yu, Tao; Cremer, Jennifer; Elston, Robert C.; Davies, M. Frances; Baptiste-Brown, Sharon; Han, Kelong; Campbell, Fiona; Paff, Melanie; Theodore, Dickens

doi:10.1016/j.jhep.2022.05.031

Cited by 34 publications

(19 citation statements)

References 25 publications

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“…A total of 65 participants received at least one dose of GSK3389404 ( 11 ), 64 of whom had evaluable plasma PK data and were included in this analysis. 1 participant from China in the 120 mg biweekly treatment arm in Part 2 (main study) was excluded from the analysis due to a nonzero GSK3389404 plasma concentration prior to the first dose, and this participant only completed day 1 of the study.…”

Section: Resultsmentioning

confidence: 99%

“… a Source: ( 11 ). b The geometric mean (range) [geometric 95% CI] is displayed, except for t max , which is shown as the median (range).…”

Section: Resultsmentioning

confidence: 99%

“…A phase 2a study (NCT03020745) was conducted in participants with chronic HBV infections in Asia, including mainland China, Hong Kong, Japan, South Korea, the Philippines, and Singapore, to assess the safety, tolerability, and PK of single and multiple doses of GSK3389404 in participants with chronic HBV infections ( 11 ). GSK3389404 demonstrated a favorable safety profile.…”

Section: Introductionmentioning

confidence: 99%

“…GSK3389404 demonstrated a favorable safety profile. Although target engagement with dose-dependent reductions in HBsAg levels was observed, no effective dosing regimen was identified ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region

Han

Ito

Elston

et al. 2023

Antimicrob Agents Chemother

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Section: Resultsmentioning

confidence: 99%

“… a Source: ( 11 ). b The geometric mean (range) [geometric 95% CI] is displayed, except for t max , which is shown as the median (range).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region

Han

Ito

Elston

et al. 2023

Antimicrob Agents Chemother

Self Cite

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“…There are also several ongoing clinical trials of antisense oligonucleotides for liver disease. One such is bepirovirsen, a second-generation 2′-O-methoxyethyl (MOE)-modified antisense phosphorothioate oligonucleotide (ClinicalTrials.gov NCT02981602) (Yuen et al, 2021), another is GSK3389404, which is formed by covalent binding of bepirovirsen to three GalNAcs (ClinicalTrials.gov NCT03020745) (Yuen et al, 2022), and finally, RO7062931, a GalNAc conjugated single stranded locked nucleic acid oligonucleotide (ClinicalTrials.gov NCT03038113) (Gane et al, 2021) for the treatment of HBV. In addition, the aforementioned DGAT2 and its corresponding antisense drug IONIS-DGAT2 RX (ClinicalTrials.gov NCT03334214) are currently undergoing phase 2 clinical trials for the treatment of NASH (Loomba et al, 2020).…”

Section: Challenges and Perspectives Of Antisense Oligonucleotide In ...mentioning

confidence: 99%

Antisense oligonucleotide is a promising intervention for liver diseases

Fan

Zou

2022

Front. Pharmacol.

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As the body’s critical metabolic organ, the liver plays an essential role in maintaining proper body homeostasis. However, as people’s living standards have improved and the number of unhealthy lifestyles has increased, the liver has become overburdened. These have made liver disease one of the leading causes of death worldwide. Under the influence of adverse factors, liver disease progresses from simple steatosis to hepatitis, to liver fibrosis, and finally to cirrhosis and cancer, followed by increased mortality. Until now, there has been a lack of accepted effective treatments for liver disease. Based on current research, antisense oligonucleotide (ASO), as an alternative intervention for liver diseases, is expected to be an effective treatment due to its high efficiency, low toxicity, low dosage, strong specificity, and additional positive characteristics. In this review, we will first introduce the design, modification, delivery, and the mechanisms of ASO, and then summarize the application of ASO in liver disease treatment, including in non-alcoholic fatty liver disease (NAFLD), hepatitis, liver fibrosis, and liver cancer. Finally, we discuss challenges and perspectives on the transfer of ASO drugs into clinical use. This review provides a current and comprehensive understanding of the integrative and systematic functions of ASO for its use in liver disease.

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Hepatitis B Virus and Hepatocellular Cancer: Molecular Mechanisms and Breakthroughs in Therapeutic Approaches

Sosa-Jurado,

Sedeño-Monge,

Márquez-Domínguez

et al. 2024

Pathogens Associated With the Development of Cancer in Humans

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Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy

Cited by 34 publications

References 25 publications

Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region

Comparison of Pharmacokinetics of the GalNAc-Conjugated Antisense Oligonucleotide GSK3389404 in Participants with Chronic Hepatitis B Infection across the Asia-Pacific Region

Antisense oligonucleotide is a promising intervention for liver diseases

Hepatitis B Virus and Hepatocellular Cancer: Molecular Mechanisms and Breakthroughs in Therapeutic Approaches

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