EASL 2018 FRI-343 REP 401协议中更新的后续分析：治疗 HBeAg阴性慢

StephenW

EASL 2018 FRI-343
Updated follow-up analysis in the REP 401 protocol: Treatment
HBeAg negative chronic hepatitis B infection with REP 2139 or
REP 2165, tenofovir disoproxil fumarate and pegylated interferon
alfa-2a
A. Vaillant1, M. Bazinet1, V. Pantea2, G. Placinta2, I. Moscalu3,
V. Cebotarescu2, L. Cojuhari2, P. Jimbei4, L. Iarovoi2, V. Smesnoi4,
T. Musteata4, A. Jucov3, A. Krawczyk5. 1Replicor Inc, Montreal, Canada;
2Nicolae Testemitanu State University of Medicine and Pharmacy,
Department of Infectious Diseases, Faculty of Postgraduate Education,
Chisinau, Moldova; 3ARENSIA Exploratory Medicine, Phase I Unit,
Republican Clinical Hospital, Chisinau, Moldova; 4Toma Ciorba
Infectious Clinical Hospital, Chisinau, Moldova; 5Universitätsklinikum
Essen, Institute for Virology, Essen, Germany
Background and Aims: The REP 401 study (NCT02565719) is
assessing the safety and efficacy of REP 2139 (clinical lead) or REP
2165 combined with tenofovir disoproxil fumarate (TDF) and
pegylated interferon α-2a (peg-IFN) in Caucasian patients with
chronic HBeAg negative HBV infection.
Method: Lead-in TDF therapy in 40 patients was followed by
randomization into an experimental group (48 weeks of TDF, peg-
IFN and REP 2139 or REP 2165) or a control group (24 weeks of TDF +
peg-IFN) who crossed over to 48 weeks of experimental therapy.
Viremia is monitored on the Abbott Architect and Realtime platforms.
Results: Therapy was well tolerated except for one withdrawal due
to pegIFN-related depression. Follow-up has been extended to 24
weeks in 18/20 experimental patients and 4–12 weeks in 17/20
crossover patients.
HBV DNA was controlled in all patients during TF lead-in and
throughout therapy. Following randomization, experimental
patients had HBsAg reductions as follows: 17/20 > 1 log from
baseline, 14/20 < 1IU/ml and 13/20 < 0.01 IU/ml. Following crossover
in control patients HBsAg reductions were as follows: 19/20 > 1 log
from baseline, 14/20 < 1IU/ml and 10/20 < 0.01 IU/ml.
HBsAg < 1 IU/ml in experimental patients was accompanied by
increases in anti-HBs (range 25–223,055 mIU/ml) in 13/14 patients
and therapeutic liver flares (ALT/AST > 5x ULN with normal synthetic
liver function) in 12/14 patients. In control patients, transaminase
flares in patients with HBsAg < 1 IU/ml were attenuated but anti-
HBsAg elevations were comparable to the experimental group.
Functional control of HBV infection (HBsAg < LLOQ, HBV DNA < LLOQ)
is persisting 24weeks after removal of therapy in 12/14 experimental
patients achieving HBsAg <1 IU/ml (REP 2139: 7/10, REP 2165: 5/10)
and is stable in the remaining 2 patients. In control patients,
functional control of HBV infection is persisting 4-12 weeks in
11/12 patients achieving HBsAg < 1 IU/ml (REP 2139: 4/10, REP 2165
7/10) with available follow-up data and is stable in the remaining
patient. Functional control of HBV infection in both groups is
accompanied by normalization of ALT/AST in all but 5 patients.
Conclusion: NAPs are effective and well tolerated in combination
with peg-IFN and TDF in HBeAg negative chronic HBV infection
and elicit the establishment of functional control of HBV infection
persisting after removal of therapy and normalization of liver
function in a majority of patients.

StephenW

EASL 2018 FRI-343
REP 401协议中更新的后续分析：治疗
HBeAg阴性慢性乙型肝炎感染与REP 2139或
REP 2165，富马酸替诺福韦二吡呋酯和聚乙二醇化干扰素
干扰素α-2a
A. Vaillant1，M. Bazinet1，V. Pantea2，G. Placinta2，I. Moscalu3，
V. Cebotarescu2，L. Cojuhari2，P. Jimbei4，L. Iarovoi2，V. Smesnoi4，
T. Musteata4，A. Jucov3，A. Krawczyk5。 1Replicor公司，加拿大蒙特利尔;
2Nicolae Testemitanu国立医药大学，
传染病学系，研究生教育学院，
基希讷乌，摩尔多瓦; 3ARENSIA探索医学，第一阶段单位，
共和国临床医院，摩尔多瓦基希讷乌; 4Toma Ciorba
感染性临床医院，摩尔多瓦基希讷乌; 5Universitätsklinikum
埃森，病毒学研究所，德国埃森
背景和目标：REP 401研究（NCT02565719）是
评估REP 2139（临床导联）或REP的安全性和有效性
2165与富马酸替诺福韦二吡呋酯（TDF）联合治疗
聚乙二醇干扰素α-2a（聚乙二醇干扰素）在高加索人患者中
慢性HBeAg阴性HBV感染。
方法：40例患者接受TDF治疗
随机分为实验组（48周的TDF，peg-
IFN和REP 2139或REP 2165）或对照组（24周的TDF +
peg-IFN），他们跨越了48周的实验性治疗。
在Abbott Architect和Realtime平台上监测病毒血症。
结果：除了一次撤药，治疗耐受性良好
pegIFN相关的抑郁症。随访已延长至24
18/20名实验患者为17周，17/20为4-12周
交叉患者。
所有患者在TF导入和治疗过程中均检测到HBV DNA
整个疗程。随机分组后，实验
患者HBsAg减少如下：17/20> 1 log
基线，14/20 <1IU / ml和13/20 <0.01IU / ml。交叉之后
在对照患者中HBsAg减少如下：19/20> 1log
从基线开始，14/20 <1IU / ml和10/20 <0.01IU / ml。
实验患者HBsAg <1 IU / ml伴有
13/14患者抗-HBs增加（范围25-223,055 mIU / ml）
和治疗性肝脏闪光（ALT / AST> 5x ULN与普通合成的
肝功能）在12/14患者。在对照患者中，转氨酶
HBsAg <1 IU / ml的患者出现荧光减弱，
HBsAg升高与实验组相当。
HBV感染的功能控制（HBsAg <LLOQ，HBV DNA <LLOQ）
在12/14实验中去除治疗后24周持续存在
达到HBsAg <1IU / ml的患者（REP 2139：7/10，REP 2165：5/10）
其余2例患者稳定。在对照患者中，
HBV感染的功能控制在4 - 12周持续存在
11/12患者达到HBsAg <1 IU / ml（REP 2139：4/10，REP 2165
7/10）与可用的后续数据，并保持稳定
患者。两组HBV感染的功能控制是
伴随ALT / AST正常化的患者除5例外。
结论：NAPs有效且耐受性良好
peg-IFN和TDF在HBeAg阴性慢性HBV感染中的作用
并引发建立HBV感染的功能控制
在取消治疗和肝脏正常化后坚持
在大多数患者中起作用。

齐欢畅

感谢