HB-110 + Entecavir:Phase 1 Clinical trials

StephenW

http://clinicaltrials.gov/show/NCT01641536
Tolerability, Immunogenicity and Efficacy of HB-110 Administered by Electroporation in Chronic Hepatitis B Patients
                         This study is ongoing, but not recruiting participants.   
                           
      First Received on June 28, 2012.            Last Updated on July 12, 2012        History of Changes      
  

Sponsor:	Genexine Co., Ltd.
Information provided by (Responsible Party):	Genexine Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01641536

    Purpose  

This study is an open label, dose escalation study using the classical 3+3 design to determine the MTD of HB-110 and assess the safety, immunogenicity and efficacy of HB-110 DNA therapeutic vaccine administered by Electroporation in combination with Entecavir in chronic hepatitis B patients.

      

Condition	Intervention	Phase
Hepatitis B, Chronic	Genetic: HB-110	Phase 1

  
  
      

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Dose-escalating Clinical Study to Evaluate the Tolerability, Immunogenicity and Efficacy of HB-110 Administered by Electroporation (EP) in an Add-on Therapy With Entecavir in Chronic Hepatitis B Patients

      

StephenW

Korean Company, Phase 1, 9 patients (using Entecavir for at least 6 months, hbvdna < 300 copies /ml, ALT <= 2 x UNL)
DNA vaccine (S, preS, Core, and Pol) + Entecavir
Vaccine delivered by Electroporation
韩国公司，第1期，9例（使用恩替卡韦至少6个月，HBVDNA<300拷贝/ ml，ALT<=2×UNL）
DNA疫苗（S，PRES，核心，和POL）+恩替卡韦
通过电穿孔交付疫苗

StephenW

http://www.ncbi.nlm.nih.gov/pubmed/19116452
Exp Mol Med. 2008 Dec 31;40(6):669-76.
Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation.Kim CY, Kang ES, Kim SB, Kim HE, Choi JH, Lee DS, Im SJ, Yang SH, Sung YC, Kim BM, Kim BG.
SourceResearch Laboratories, Dong-A Pharm. Co., Ltd. Yongin 449-900, Korea.

AbstractPulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.

Exp 分子医学。 2008年12月31日;40（6）:669-76。
增加体内免疫效力的HB-110，一种新型的治疗性乙肝DNA疫苗，通过电。
金CY，康ES，金SB，金贺，财津海，李副秘书长，IM律政司司长，杨SH，宋远超，金保函，金BM。
源

研究实验室，一个医药。有限公司龙仁市449-900，韩国。
抽象

脉冲诱导通透细胞膜，通常称为电（EP），已使用多年，作为一种工具，增加组织中的高分子吸收，包括核酸，基因治疗的应用，这一技术已被证明导致改善免疫原性。在这项研究中，我们评估作为一种工具，以提高疗效HB-110，一种新型的DNA疫苗对慢性乙型肝炎的治疗，现在在韩国的临床研究第一阶段的EP的效用。 HB-110小鼠的效力被证明是改进的EP。起效迅速的抗原表达和较高的电脉冲治疗的小鼠的体液免疫和细胞反应的幅度透露，EP可能使中引起类似的反应幅度来实现的，通过常规管理所需的DNA疫苗的用量大幅减少。这项研究还表明，在4周的时间间隔，EP为基础的疫苗接种引起细胞免疫反应比常规免疫接种引起反应每隔2周高2倍左右。这些结果可能提供了一个理由，以减少临床剂量和增加在多剂量的疫苗接种计划的剂量之间的间隔。电脉冲也引起反对4抗原表达HB-110更平衡的免疫反应：S，压力，核心，和pol。

MP4

韩国治疗性乙肝DNA疫苗获批准国际2期临床试验
http://www.hbvhbv.com/forum/foru ... fromuid-320872.html
韩国乙肝治疗性DNA疫苗
http://www.hbvhbv.com/forum/foru ... fromuid-320872.html

StephenW

回复 MP4 的帖子

"HB-100 expressing HBV S, pre S1/S2, core, polymerase, X protein and human IL-12 mutant (hIL-12N222L) intramuscularly"

HB  - 100表达HBV的S前的S1/S2，核心，聚合酶，X蛋白与人类IL-12的突变体（HIL12N222L）肌肉注射

HB-110 similar to HB-100, without X protein & IL-12 mutant, delivery is different, and patients are different, hopefully results are better.HB-110 HB-100相似，无X蛋白与IL-12的突变体，传递
是不同的，和病人
不同，希望结果是更好的。

MP4

StephenW 发表于 2012-8-12 10:31
回复 MP4 的帖子

"HB-100 expressing HBV S, pre S1/S2, core, polymerase, X protein and human IL-12 mu ...

你错了，110不可能是精简版。
HB-110 consists of three plasmids, pGX10-S/L, pGX10-C/P, and pGX10-hIL-12m, which encode for the HBV envelope proteins (S, L), core protein, polymerase, and human IL-12
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679337/

MP4

去掉了X蛋白。X蛋白本身可能有致癌的风险。

StephenW

回复 MP4 的帖子

Yes, you are right. It also includes gene for IL-12.

MP4

This result was quite exciting, considering that the appearance of anti-HBs antibodies is a serological marker of complete recovery from hepatitis B. The potency of the humoral response elicited by EP was confirmed in a transgenic mouse model in which the HBV full genome replicates in the liver. Vaccination with EP induced HBsAg seroconversion in three out of six animals (50%), whereas in the group treated with vaccine alone, only one out of six animals (16.7%) showed seroconversion.

咬牙硬挺

看二位的意思，这个疫苗有戏啊！棒子加油斯迷达