EASL2019 PS-078 HepT细胞HBV特异性免疫治疗的1b期评估 nuc控制，eAg

StephenW

PS-078
A phase 1b evaluation of HepTcell HBV-specific immunotherapy in
nuc-controlled, eAg negative chronic HBV infection
Young-Suk Lim2, David Mutimer3, Jeong Heo4, Won Young Tak5,
William Rosenberg6, Byoung Kuk Jang7, Yoon Jun Kim8, Dan Forton9,
Sybil Tasker10, Bertrand Georges11. 1Imperial College, London, United
Kingdom; 2Asan Medical Center, Seoul, Korea, Rep. of South; 3Queen
Elizabeth Medical Centre, Birmingham, United Kingdom; 4Pusan
National University, Busan, Korea, Rep. of South; 5Kyungpook National
University, Daegu, Korea, Rep. of South; 6Royal Free Hospital, London,
United Kingdom; 7Keimyung University Dongsan Medical Center, Daegu,
Korea, Rep. of South; 8Seoul National University, Seoul, Korea, Rep. of
South; 9St. George’s Hospital, London, United Kingdom; 10Altimmune,
Inc, Gaithersburg, MD, United States; 11Altimmune, Inc, London,
United Kingdom
Email: [email protected]
Background and aims: It iswell understood that cellular immunity is
key to HBV control. HepTcell is an immunotherapeutic syntheticproduct composed of 9 peptides designed to drive T cell-immune
responses against conserved regions of several HBV antigens. IC31® is
a TLR-9 agonist-based adjuvant formulation designed to minimize
systemic exposure.
Method: 60 HBeAg- subjectswell controlled on entecavir or tenofovir
were randomized to low and high dose peptides, with and without
IC31, placebo, and IC31 alone across 3 dose-escalating cohorts. All
subjects received 3 injections 28 days apart and were followed for 6
months after last injection. End points included patient and physician
assessment of reactogenicity, adverse events including changes in
transaminase levels, IFNγ-ELISpot of cultured PBMCs, and quantitative
HBsAg.
Results: All doses were well tolerated with no SAEs or liver flares.
The placebo group had higher baseline ELISpot responses, making
immunology results difficult to interpret, but after the 3 injections,
both adjuvanted peptide groups had increases in ELISpot spots/106
PBMC against the vaccine peptides compared to baseline values:
Low + IC31 = +5608 (95% CI 0, +17483); High+ IC31 = +4804 (95% CI
+2933, +10192); Placebo = +167 (95% CI −6717, +6692). Most of the
response was driven by peptides derived from HBV polymerase
antigen. Only one subject, a placebo recipient, had quantitative
HBsAg decline > 0.5 log.
Conclusion: HepTcell immunotherapywaswell tolerated and elicited
HBV-specific immune responses in patients with well controlled
HBeAg-negative chronic HBV. No effect on HBsAg was seen in this
short course monotherapy study, but the safety and immunogenicity
supports further evaluation in additional HBV populations and in
combination with other novel products.

StephenW

PS-078
HepT细胞HBV特异性免疫治疗的1b期评估
nuc控制，eAg阴性慢性HBV感染
Young-Suk Lim2，David Mutimer3，Jeong Heo4，Won Young Tak5，
William Rosenberg6，Byoung Kuk Jang7，Yoon Jun Kim8，Dan Forton9，
Sybil Tasker10，Bertrand Georges11。 1英国伦敦大学
王国; 2Asan医疗中心，韩国首尔，南方代表; 3Queen
伊丽莎白医疗中心，英国伯明翰; 4Pusan
国立大学，韩国釜山，南方代表; 5Kyungpook National
大学，韩国大邱，南方代表; 6Royal免费医院，伦敦，
英国; 7大学东山医学中心，大邱
韩国，南方众议员; 8首尔国立大学，韩国首尔，共和国
南; 58.1。乔治医院，英国伦敦; 10Altimmune，
Inc，Gaithersburg，MD，United States; 11Altimmune，Inc，伦敦，
英国
电子邮件：[email protected]
背景和目的：可以理解，细胞免疫是
HBV控制的关键。 HepTcell是一种免疫治疗合成产品，由9种肽组成，旨在驱动T细胞免疫
对几种HBV抗原的保守区域的反应。 IC31®是
基于TLR-9激动剂的佐剂配方，旨在最大限度地减少
全身暴露。
方法：60例HBeAg-受试者对恩替卡韦或替诺福韦进行控制
随机分为低剂量和高剂量肽，有和没有
IC31，安慰剂和IC31单独用于3个剂量递增的队列。所有
受试者间隔28天接受3次注射，随访6次
最后一次注射后数月。终点包括患者和医生
评估反应原性，不良事件，包括变化
转氨酶水平，培养的PBMCs的IFNγ-ELISpot和定量
乙肝表面抗原。
结果：所有剂量均耐受良好，无SAE或肝脏发作。
安慰剂组的基线ELISpot反应较高
免疫学结果难以解释，但在3次注射后，
两种佐剂化肽组的ELISpot斑点均增加/ 106
与基线值相比，针对疫苗肽的PBMC：
低+ IC31 = +5608（95％CI 0，+ 17483）;高+ IC31 = + 4804（95％CI
+2933，+ 10192）;安慰剂= + 167（95％CI -6717，+ 6692）。大部分的
响应由源自HBV聚合酶的肽驱动
抗原。只有一个受试者，一个安慰剂接受者，有定量
HBsAg下降> 0.5 log。
结论：HepT细胞免疫治疗耐受并引发
控制良好的患者的HBV特异性免疫反应
HBeAg阴性慢性HBV。对此没有影响HBsAg
短程单药治疗研究，但安全性和免疫原性
支持进一步评估其他HBV人群和
与其他新产品相结合。