B-Clear 二期 b 研究设计：评估 Bepirovirsen 治疗慢性乙型肝炎病毒感染患者的疗效和安全性。
B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection.
机构信息
R&D Clinical Sciences Hepatology, GSK, 5 Moore Drive, PO Box 13398, RTP, Durham, NC, 27709-3398, USA.
GSK, Stevenage, UK.
出版信息
Adv Ther. 2023 Sep;40(9):4101-4110. doi: 10.1007/s12325-023-02531-z. Epub 2023 Jul 1.
INTRODUCTION
Bepirovirsen (GSK3228836) is an antisense oligonucleotide that induced rapid and prolonged hepatitis B surface antigen (HBsAg) reduction with a favorable safety profile following 4 weeks of treatment in participants with chronic hepatitis B virus (HBV) infection. The objective of the phase 2b study B-Clear is to access the efficacy and safety of bepirovirsen in participants with chronic HBV infection.
METHODS
B-Clear is a phase 2b, multicenter, randomized, partial-blind (sponsor/participant-blinded, investigator-unblinded) study in participants with chronic HBV infection receiving stable nucleos(t)ide analogue (On-NA) or not currently receiving NA therapy (Not-on-NA). Eligibility criteria included HBsAg > 100 IU/mL, HBV DNA < 90 IU/mL (On-NA) or > 2000 IU/mL (Not-on-NA), and alanine aminotransferase ≤ 2 × upper limit of normal (ULN; On-NA) or < 3 × ULN (Not-on-NA). Participants were randomized 3:3:3:1 to one of four treatment arms, with treatment administered weekly as subcutaneous injections with or without loading doses (LD) on days 4 and 11: bepirovirsen 300 mg (with 300 mg LD) for 24 weeks; bepirovirsen 300 mg (with 300 mg LD) for 12 weeks then bepirovirsen 150 mg for 12 weeks; bepirovirsen 300 mg (with 300 mg LD) for 12 weeks then placebo for 12 weeks; placebo for 12 weeks (with placebo LD) then bepirovirsen 300 mg without LD for 12 weeks.
PLANNED OUTCOMES
The primary endpoint of the study was HBsAg < lower limit of detection and HBV DNA < lower limit of quantification for 24 weeks after the end of bepirovirsen treatment in the absence of rescue medication. The study enrolled 457 participants (On-NA, n = 227; Not-on-NA, n = 230) and the last patient visit occurred in March 2022. The novel design of the B-Clear study will allow assessment of HBsAg and HBV DNA seroclearance post bepirovirsen treatment discontinuation in the presence and absence of background NA therapy.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT04449029; GSK study 209668).
简介
Bepirovirsen（GSK3228836）是一种反义寡核苷酸药物，在慢性乙型肝炎病毒（HBV）感染患者中，经过 4 周治疗后，可快速、持续地降低乙型肝炎表面抗原（HBsAg），且安全性良好。B-Clear 是一项评估 Bepirovirsen 在慢性 HBV 感染患者中的疗效和安全性的 2b 期研究。
方法
B-Clear 是一项 2b 期、多中心、随机、部分盲（研究者开放）研究，纳入正在接受核苷（酸）类似物（NAs）治疗（On-NA）或未接受 NAs 治疗（Not-on-NA）的慢性 HBV 感染患者。入选标准包括 HBsAg＞100IU/ml、HBV DNA＜90IU/ml（On-NA）或＞2000IU/ml（Not-on-NA），以及丙氨酸氨基转移酶（ALT）≤2×正常值上限（ULN；On-NA）或＜3×ULN（Not-on-NA）。患者按 3：3：3：1 的比例随机分配至 4 个治疗组，每周接受一次皮下注射，第 4 天和第 11 天给予负荷剂量（LD）：Bepirovirsen 300mg（联合 300mg LD）治疗 24 周；Bepirovirsen 300mg（联合 300mg LD）治疗 12 周，然后 Bepirovirsen 150mg 治疗 12 周；Bepirovirsen 300mg（联合 300mg LD）治疗 12 周，然后安慰剂治疗 12 周；安慰剂治疗 12 周（联合安慰剂 LD），然后 Bepirovirsen 300mg 无 LD 治疗 12 周。
研究计划
该研究的主要终点为 Bepirovirsen 治疗结束后 24 周内，在无挽救治疗药物的情况下，HBsAg＜检测下限且 HBV DNA＜定量下限。该研究共纳入 457 例患者（On-NA，n=227；Not-on-NA，n=230），最后一次患者访视于 2022 年 3 月。B-Clear 研究的新颖设计将允许评估 Bepirovirsen 治疗停药后在有或无背景 NA 治疗的情况下 HBsAg 和 HBV DNA 血清学清除情况。
试验注册
ClinicalTrials.gov（NCT04449029；GSK 研究 209668）。
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