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标题: AASLD2019[705]功能控制/固化的持续分析 遵循REP 2139-CA和HBV和HDV [打印本页]

作者: StephenW    时间: 2019-10-25 17:50     标题: AASLD2019[705]功能控制/固化的持续分析 遵循REP 2139-CA和HBV和HDV

705
ONGOING ANALYSIS OF FUNCTIONAL CONTROL / CURE OF
HBV AND HDV INFECTION FOLLOWING REP 2139-CA AND
PEGYLATED INTERFERON ALPHA-2a THERAPY IN PATIENTS
WITH CHRONIC HBV / HDV CO-INFECTION: 3-YEAR FOLLOWUP
RESULTS FROM THE REP 301-LTF STUDY
Michel Bazinet1, Victor Pântea2, Valentin Cebotarescu2, Lilia
Cojuhari2, Pavlina Jimbei3, Adalbert Krawczyk4,5, Ulf Dittmer6
and Andrew Vaillant1, (1)Replicor Inc., (2)Department of
Infectious Diseases, Nicolae Testemiţanu State University of
Medicine and Pharmacy, (3)Toma Ciorbă Infectious Clinical
Hospital, (4)Institute for Virology, University Hospital Essen,
University of Duisburg-Essen, (5)Department of Infectious
Diseases, University Hospital Essen, University of Duisburg-
Essen, (6)Institute of Virology, University Hospital Essen,
University of Duisburg-Essen
Background: HBV / HDV co-infection represents a
significant unmet medical need, causes rapid progression
of liver disease and has no approved therapy REP 2139 is
a nucleic acid polymer which blocks the assembly of HDV
and HBV subviral particles, preventing release of HDV and
HBsAg while simultaneously lowering intracellular HBsAg
REP 2139 also directly targets HDAg to block HDV replication
upstream from its secretion REP 2139-Ca and pegylated
interferon clear both HBsAg and HDV RNA in the majority of
patients during therapy and initial follow-up demonstrated the
establishment of functional control of HBV (HBV DNA ≤ 2000
IU/mL, normal ALT) in 5/12 patients, functional control of HDV
(HBV RNA > 2 log10 reduction from baseline, normal ALT) in
8/12 patients. Functional cure of HDV (HDV RNA TND) was
further established in 7/12 patients and functional cure of HBV
(HBsAg < LLOQ, HBV TND) was further established in 4/12
patients A three-year supplemental follow-up study (REP
301-LTF, NCT02876419) is currently examining the longterm
stability of the functional control / cure of HBV and HDV
infection achieved in the REP 301 study (NCT02233075)
Methods: All REP 301 study participants completing therapy
were enrolled in the REP 301-LTF study Follow up safety
and efficacy evaluations are scheduled every 6 months
(for a period of three years) following the original 24-week
follow-up in the REP 301 study. Virologic status was verified
using Architect (HBV) and Robogene MKII (HDV RNA) test
platforms Hepatic stiffness was monitored by Fibroscan
Results: Currently, 5/11 participants have completed 3 years
of follow -up and 6/11 2 5 years of follow-up Functional
control of HBV, functional control/cure of HDV and ALT
normalization previously established is persisting in all
patients One participant transitioned from functional cure of
HBV at 2 years of follow-up to functional control at 2.5 years
follow-up (currently 0.15 IU/mL HBsAg, HBV DNA < LLOQ).
Two participants with functional cure of HDV have shown
improvement in their functional control of HBV with HBV DNA
declines transitioning from 183 IU/mL to TND and from 1904
to 105 IU/mL respectively Median hepatic stiffness continues
to decline or is stable in all participants Conclusion:
Functional control / cure of HDV and HBV infection achieved
with REP 2139 and pegIFN is stable at 3 years follow-up
and is associated with persistently normal liver function and
progressive reduction in median hepatic stiffness.
作者: StephenW    时间: 2019-10-25 17:51

705
功能控制/固化的持续分析
遵循REP 2139-CA和HBV和HDV感染
病人的聚乙二醇化干扰素α-2a治疗
慢性HBV / HDV合并感染:3年随访
REP 301-LTF研究的结果
Michel Bazinet1,VictorPântea2,Valentin Cebotarescu2,Lilia
Cojuhari2,Pavlina Jimbei3,Adalbert Krawczyk4,5,Ulf Dittmer6
和Andrew Vaillant1,(1)Replicor Inc。,(2)
NicolaeTestemiţanu国立大学传染病
医药,(3)TomaCiorbă传染性临床
医院,埃森大学医院(4)病毒学研究所,
杜伊斯堡-埃森大学,(5)传染系
杜伊斯堡大学埃森大学附属医院疾病
埃森(6)埃森大学医院病毒研究所,
杜伊斯堡-埃森大学
背景:HBV / HDV合并感染代表
大量未满足的医疗需求,导致快速进展
肝病并且没有批准的疗法REP 2139是
阻止HDV装配的核酸聚合物
和HBV亚病毒颗粒,防止HDV和
HBsAg同时降低细胞内HBsAg
REP 2139还直接针对HDAg来阻止HDV复制
分泌REP 2139-Ca上游并聚乙二醇化
干扰素清除了大多数人的HBsAg和HDV RNA
患者在治疗和最初的随访过程中表现出
建立HBV功能控制(HBV DNA≤2000
IU / mL,5/12例患者的正常ALT),HDV的功能控制
(HBV RNA>从基线水平下降2 log10,正常ALT)
8/12患者。 HDV(HDV RNA TND)的功能治疗为
在7/12患者中进一步确立并治愈乙肝
(HBsAg <LLOQ,HBV TND)在4/12中进一步建立
患者一项为期三年的补充随访研究(REP
301-LTF,NCT02876419)目前正在研究长期
功能控制的稳定性/ HBV和HDV的治愈
REP 301研究(NCT02233075)感染
方法:所有REP 301研究参与者均完成治疗
被纳入REP 301-LTF研究
每6个月安排一次疗效评估
(最初的24周后)(三年)
REP 301研究的后续行动。病毒学状态已验证
使用Architect(HBV)和Robogene MKII(HDV RNA)测试
通过Fibroscan监测肝硬度
结果:目前,有5/11名参与者已完成3年
随访和6/11 2 5年的随访功能
HBV控制,HDV和ALT的功能控制/治疗
以前建立的规范化在所有领域都持续存在
一名患者从功能性治愈过渡到
随访2年后进行HBV,2.5年后进行功能控制
随访(目前0.15 IU / mL HBsAg,HBV DNA <LLOQ)。
两名具有HDV功能治愈的参与者已显示
HBV DNA改善对HBV的功能控制
从183 IU / mL下降到TND和1904年
分别达到105 IU / mL
下降或稳定的所有参与者结论:
功能控制/治愈HDV和HBV感染
REP 2139和pegIFN在3年的随访中稳定
并与持续正常的肝功能有关
逐渐降低中位肝硬度。




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