AASLD2016[LB-7] REP 2139-Mg或REP2165-Mg的初步安全性和有效性 与替诺

StephenW

LB-7
Preliminary safety and efficacy of REP 2139-Mg or REP
2165-Mg used in combination with tenofovir disoproxil
fumarate and pegylated interferon alpha 2a in treatment
naïve Caucasian patients with chronic HBeAg negative
HBV infection
Michel Bazinet1, Victor Pantea2, Gheorghe Placinta2, Iurie
Moscalu3, Valentin Cebotarescu2, Lilia Cojuhari4, Paulina Jimbei4,
Liviu Iarovoi2, Valentina Smesnoi4, Tatiana Musteata4, Alina
Jucov2,3, Adalbert Krawczyk5, Andrew Vaillant1; 1Replicor Inc.,
Montreal, QC, Canada; 2Department of Infectious Diseases, Nicolae
Testemitanu State University of Medicine and Pharmacy, Chisinau,
Moldova (the Republic of); 3ARENSIA Exploratory Medicine,
Republican Clinical Hospital, Chisinau, Moldova (the Republic of);
4Toma Ciorba Infectious Clinical Hospital, Chisinau, Moldova (the
Republic of); 5Institute for Virology, University Hopsital at the University
of Duisburg-Essen, Essen, Germany
Nucleic acid polymers (NAPs) block HBsAg release from HBV
infected hepatocytes. The NAP REP 2139 clears serum HBsAg
in chronic HBV infection, improving the efficacy of immunotherapy
and facilitating establishment of functional control off
treatment. The REP 401 protocol (NCT02565719) is a randomized,
controlled trial assessing the safety and efficacy of
REP 2139 and a REP 2139 derivative with improved clearance
(REP 2165) in combination with tenofovir disoproxil fumarate
(TDF) and pegylated interferon alpha 2a (peg-IFN) in treatment
naïve patients with chronic HBeAg negative HBV infection.
Forty patients will receive 26 weeks of lead-in TDF (300mg PO
qD) followed by randomization (1:1) into experimental and
control groups. The experimental group will receive 48 weeks
of TDF, peg-IFN (180ug SC qW) and REP 2139-Mg or REP
2165-Mg (1:1, 250 mg IV infusion qW). Patients in the control
group will receive 48 weeks of TDF + peg-IFN but will crossover
to 48 weeks of experimental therapy in the absence of a
3 log drop in HBsAg after 24 weeks of peg-IFN. Serum viremia
is being monitored offsite at the Institute for Virology, University
Hospital at the University Duisburg-Essen, Essen, Germany.
Enrolment is complete and 22 patients have received ≥ 12
weeks of treatment in control and experimental groups. After
TDF lead-in, most patients have serum HBV DNA ≤ 10 IU / ml
prior to peg-INF exposure. Triple combination therapy is well
tolerated in all patients and no infusion reactions have been
observed with either NAP. Serum HBsAg reductions, increases
in serum anti-HBs or serum ALT / AST / GGT flares were negligible
or absent in all patients during TDF lead-in and in the
control group to date. In patients having completed 12 weeks
of NAP exposure, 4 /5 receiving REP 2139-Mg and 4 / 6
patients receiving REP 2165-Mg have experienced multilog
reductions in serum HBsAg and increases in serum anti-HBs.
Two patients in the REP 2139-Mg group experienced multilog
drops after only 4 weeks. An additional REP 2165-Mg patient
(a 5th responder in this group) has also experienced a multilog
HBsAg drop after 4 weeks of exposure. NAP-mediated HBsAg
reductions are accompanied by otherwise asymptomatic ALT /
AST / GGT flares substantially greater than those in the control
group. These preliminary data demonstrate the tolerability and
efficacy of REP 2139 and REP 2165 when used in combination
with peg-IFN and TDF in patients with HBeAg negative chronic
HBV infection. Early clearance in serum HBsAg mediated by
NAPs is correlated with the onset of an intense transaminase
flare and suggests NAP-mediated HBsAg clearance improves
the efficacy of peg-IFN in this patient population.
Disclosures:
Michel Bazinet - Board Membership: Replicor Inc.; Employment: Replicor Inc.;
Management Position: Replicor Inc.; Patent Held/Filed: Replicor Inc.; Stock
Shareholder: Replicor Inc.
Andrew Vaillant - Employment: Replicor; Stock Shareholder: Replicor
The following people have nothing to disclose: Victor Pantea, Gheorghe Placinta,
Iurie Moscalu, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei, Liviu Iarovoi,
Valentina Smesnoi, Tatiana Musteata, Alina Jucov, Adalbert Krawczyk

StephenW

AASLD2016 [LB-7]
REP 2139-Mg或REP2165-Mg的初步安全性和有效性
与替诺干扰素α2a组合使用HBeAg阴性患者


REP 2139-Mg或REP的初步安全性和有效性
2165-Mg与替诺福韦地索普西组合使用
富马酸盐和聚乙二醇化干扰素α2a
初始白种人慢性HBeAg阴性患者
HBV感染
Michel Bazinet1，Victor Pantea2，Gheorghe Placinta2，Iurie
Moscalu3，Valentin Cebotarescu2，Lilia Cojuhari4，Paulina Jimbei4，
Liviu Iarovoi2，Valentina Smesnoi4，Tatiana Musteata4，Alina
Jucov2,3，Adalbert Krawczyk5，Andrew Vaillant1; 1Replicor Inc.，
蒙特利尔，QC，加拿大;传染病，Nicolae
Testemitanu国立医学药学大学，基希纳乌，
摩尔多瓦共和国3ARENSIA探索医学，
共和国临床医院，基希纳乌，摩尔多瓦共和国;
4Toma Ciorba传染性临床医院，基希纳乌，摩尔多瓦（
共和国）; 5大学Hopsital大学病毒学研究所
的杜伊斯堡 - 埃森，埃森，德国
核酸聚合物（NAP）阻断HBsAg从HBV释放
感染的肝细胞。 NAP REP 2139清除血清HBsAg
在慢性HBV感染中，提高免疫治疗的疗效
并促进功能控制的建立
治疗。 REP 401协议（NCT02565719）是一种随机，
控制试验评估其安全性和有效性
REP 2139和REP 2139衍生物
（REP 2165）与替诺福韦地索普西富马酸盐组合
（TDF）和聚乙二醇化干扰素α2a（peg-IFN）
初次接受慢性HBeAg阴性HBV感染的患者。
40例患者将接受26周的含铅TDF（300mg PO
qD），随后随机化（1：1）进入实验和
控制组。实验组将接受48周
的TDF，peg-IFN（180ug SC qW）和REP 2139-Mg或REP
2165-Mg（1:1,250mg IV输注qW）。病人在控制
组将接受48周的TDF + peg-IFN，但将交叉
至48周的实验治疗
在peg-IFN的24周后HBsAg的3log下降。血清病毒血症
在大学病毒学研究所外部进行监测
杜塞尔多夫大学医院，德国埃森。
入组完成，22例患者≥12岁
周在对照组和实验组中的治疗。后
TDF导入，大多数患者血清HBVDNA≤10IU / ml
在peg-INF暴露之前。三联组合疗法很好
在所有患者中都耐受且没有输注反应
观察到与NAP。血清HBsAg减少，增加
在血清抗HBs或血清ALT / AST / GGT耀斑是可以忽略不计的
或在TDF导入期间和在所有患者中不存在
控制组。在完成12周的患者中
的NAP暴露，4/5接受REP 2139-Mg和4/6
接受REP 2165-Mg的患者经历了多日
血清HBsAg的减少和血清抗HBs的增加。
REP 2139-Mg组中的两个患者经历多log
仅4周后下降。另外一名REP 2165-Mg患者
（这个组中的第五响应者）也经历了多日志
暴露4周后HBsAg下降。 NAP介导的HBsAg
减少伴有否则无症状的ALT /
AST / GGT明显大于对照组
组。这些初步数据证明了耐受性
REP 2139和REP 2165的组合使用时的效力
与peg干扰素和TDF在HBeAg阴性慢性患者
HBV感染。早期清除血清HBsAg介导
NAP与强转氨酶的发作相关
flare和建议NAP介导的HBsAg清除改善
在该患者群体中peg-IFN的功效。
披露：
Michel Bazinet - 董事会成员：Replicor Inc.;就业：复制公司。
管理职位：Replicor Inc.;专利/文件：Replicor Inc.;股票
股东：Replicor Inc.
Andrew Vaillant - 就业：复制;股票股东：复制
以下人没有什么可披露：Victor Pantea，Gheorghe Placinta，
Iurie Moscalu，Valentin Cebotarescu，Lilia Cojuhari，Paulina Jimbei，Liviu Iarovoi，
Valentina Smesnoi，Tatiana Musteata，Alina Jucov，Adalbert Krawczyk