IIb试验的体内电穿孔介导的双重质粒乙型肝炎病毒DNA疫苗在

StephenW

World J Gastroenterol. 2017 Jan 14;23(2):306-317. doi: 10.3748/wjg.v23.i2.306.
Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy.Yang FQ1, Rao GR1, Wang GQ1, Li YQ1, Xie Y1, Zhang ZQ1, Deng CL1, Mao Q1, Li J1, Zhao W1, Wang MR1, Han T1, Chen SJ1, Pan C1, Tan DM1, Shang J1, Zhang MX1, Zhang YX1, Yang JM1, Chen GM1.
Author information

• 1Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
  

AbstractAIM: To assess the efficacy and safety of in vivo electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B.
METHODS: Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, n = 109) or LAM + placebo (control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12 (start of treatment with vaccine or placebo, SOT), 16, 24, and 36 (end of treatment with vaccine or placebo, EOT).
RESULTS: In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir (ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeAg seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations.
CONCLUSION: The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.


KEYWORDS: Chronic hepatitis B; DNA vaccine; In vivo electroporation; Lamivudine-resistant mutants; Randomized placebo-controlled trial

PMID:28127204DOI:10.3748/wjg.v23.i2.306

StephenW

世界胃肠病学杂志。 2017 Jan 14; 23（2）：306-317。 doi：10.3748 / wjg.v23.i2.306。

Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients in lamivudine therapy。

Yang FQ1，Rao GR1，Wang GQ1，Li YQ1，Xie Y1，Zhang ZQ1，Deng CL1，Mao Q1，Li J1，Zhao W1，Wang MR1，Han T1，Chen SJ1，Pan C1，Tan DM1，Shang J1，Zhang MX1 ，Zhang YX1，Yang JM1，Chen GM1。
作者信息

    1Fu-Qiang Yang，Gui-Rong Rao，Guang-Ming Chen，Liver Disease Research Center，458 Hospital of PLA，Guangzhou 510062，Guangdong Province，China。

抽象
目标：

评估体内电穿孔（EP）介导的双重质粒乙型肝炎病毒（HBV）DNA疫苗与安慰剂在慢性乙型肝炎患者中用拉米夫定（LAM）进行顺序联合治疗的疗效和安全性。
方法：

二百二十五名患者被随机分配接受LAM +疫苗（疫苗组，n = 109）或LAM +安慰剂（对照组，n = 116）。 LAM治疗持续72周。在第12周（用疫苗或安慰剂治疗开始，SOT），16,24和36（用疫苗或安慰剂治疗结束，EOT），通过EP介导的肌内注射，患者接受DNA疫苗或安慰剂。
结果：

在改良的意向治疗人群中，与对照组相比，在EOT后第12周，更多患者在疫苗组中HBV DNA> 2log 10 IU / mL下降。获得在EOT后第28周时具有不可检测的HBV DNA的患者数量的差异的趋势。不良事件相似。在由于LAM抗病毒失败而在ADV给药后立即排除在每个时间点排除阿德福韦（ADV）附加病例的动态每个方案组中，更多患者在疫苗组中HBV DNA> 2log 10 IU / mL降低在EOT后12周和28周与对照组比较。还观察到在疫苗组中EOT之后第28周更多的患者具有不可检测的HBV DNA。在第12周时病毒载量<1000拷贝/ mL的患者中，在EOT后36周，更多的患者在疫苗组中获得了比在对照组中的HBeAg血清学转换，以及更少的病毒学突破和YMDD突变。
结论：

使用HBV DNA疫苗未能达到主要终点。 HBV DNA疫苗仅对在LAM化疗下实现初始病毒学应答的受试者有益。
关键词：

慢性乙型肝炎; DNA疫苗;体内电穿孔;拉米夫定耐药突变体;随机安慰剂对照试验

PMID：
    28127204
DOI：
    10.3748 / wjg.v23.i2.306

MP4

广州药业集团白云山益甘生物
广州解放军458医院
要进一步扩大研究数量进行确证性研究； 下一步临床研究的联合用药
建议由拉米夫定调整为恩替卡韦