title: Phase IIb trial ofin vivoelectroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy.
abstract: OBJECTIVE
  To assess the efficacy and safety ofin vivoelectroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccinevsplacebo 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 log10IU/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 log10IU/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Yang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Rao
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Gui-Qiang
authors.initials: GQ
authors.lastname: Wang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Yue-Qi
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Zhan-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Cun-Liang
authors.initials: CL
authors.lastname: Deng
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Mao-Rong
authors.initials: MR
authors.lastname: Wang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Pan
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Tan
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Yue-Xin
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Fu-Qiang Yang, Gui-Rong Rao, Guang-Ming Chen, Liver Disease Research Center, 458 Hospital of PLA, Guangzhou 510062, Guangdong Province, China.
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Chen
mesh_terms: D000328:Adult; D004279:DNA, Viral / Q000008:administration & dosage / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000187:drug effects; D018274:Electroporation / Q000379:methods*; D005260:Female; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007273:Injections, Intramuscular; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010957:Plasmids; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D017325:Hepatitis B Vaccines; D018894:Reverse Transcriptase Inhibitors; D019444:Vaccines, DNA; D019259:Lamivudine
keywords: Chronic hepatitis B; DNA vaccine; In vivo electroporation; Lamivudine-resistant mutants; Randomized placebo-controlled trial