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

• Published in: World journal of gastroenterology : WJG Vol. 23; no. 2; pp. 306 - 317
• Main Authors: Yang, Fu-Qiang, Rao, Gui-Rong, Wang, Gui-Qiang, Li, Yue-Qi, Xie, Yao, Zhang, Zhan-Qing, Deng, Cun-Liang, Mao, Qing, Li, Jun, Zhao, Wei, Wang, Mao-Rong, Han, Tao, Chen, Shi-Jun, Pan, Chen, Tan, De-Ming, Shang, Jia, Zhang, Ming-Xiang, Zhang, Yue-Xin, Yang, Ji-Ming, Chen, Guang-Ming
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.01.2017
• Subjects: Adult; Clinical Trials Study; DNA, Viral - administration & dosage; DNA, Viral - adverse effects; DNA, Viral - isolation & purification; DNA, Viral - therapeutic use; Double-Blind Method; Drug Resistance, Viral - drug effects; Electroporation - methods; Female; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - adverse effects; Hepatitis B Vaccines - therapeutic use; Hepatitis B virus - genetics; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - drug therapy; Humans; Injections, Intramuscular; Lamivudine - administration & dosage; Lamivudine - therapeutic use; Male; Plasmids; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - therapeutic use; Treatment Outcome; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - therapeutic use; Viral Load; Young Adult; DNA vaccine; Randomized placebo-controlled trial; Chronic hepatitis B; Lamivudine-resistant mutants; In vivo electroporation
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v23.i2.306

To assess the efficacy and safety of electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B. Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, = 109) or LAM + placebo (control group, = 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). In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log 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 log 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. 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.