Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens With or Without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Solicited and unsolicited serious adverse events
研究概览
简要总结
Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens with or without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth
详细描述
HIVIS DNA and MVA-CMDR vaccines induce immune responses important for clearing infected cells: broad HIV-specific CD8+ cytotoxic T cells, potent antibodydependent cellular cytotoxicity (ADCC), and binding antibody (Ab) and neutralizing antibody (NAb). The study include early treated children because of their healthy immunity and small HIV reservoirs. Giving licensed vaccine, Cervarix®, against human papilloma virus (HPV) that contains toll-like receptor (TLR) 4 agonist with HIVIS DNA could increase DNA antigen loading on dendritic cells and promote adaptive immune responses to the HIV vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 9 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1 (n=10): HIVIS DNA / MVA-CMDR
Arm 1 (n=10) will receive 1500 micrograms (0.5ml) HIVIS DNA IM by needle-free injection at weeks 0 and 4 followed by intramuscular (IM) needle injection of 1 X 108 IU/mL (1ml) MVA-CMDR at weeks 24 and 36 in the same arm as HIVIS DNA.
Participants who have been randomized to receive HIVIS DNA and MVA-CMDR alone (ARM 1) will be administered Cervarix after week 72, the last study follow-up visit, if required.
干预措施: HIVIS DNA/MVA-CMDR (Biological)
Arm 2 (n=10): HIVIS DNA + Cervarix/ / MVA-CMDR
Arm 2 (n=10) will receive 0.5 ml of Cervarix IM by needle injection followed by 1500 micrograms (0.5ml) per injection of HIVIS DNA IM by a needle-free injection device in the skin above (proximal to) the Cervarix injection (within 1.5 cm). They will receive 1 X 108 IU/mL (1ml) MVA-CMDR IM by needle injection at weeks 24 and 36 in the same arm as HIVIS DNA. They will also receive 0.5 ml Cervarix at the time of the first MVACMDR injection in the opposite arm from the MVA injection at week 24.
干预措施: HIVIS DNA + Cervarix and MVA-CMDR (Biological)
Arm 3 (n=5): Cervarix
Arm 3 (n=5) will receive 0.5 ml of Cervarix by IM needle injection at weeks 0, 4 and 24.
干预措施: Cervarix (Biological)
结局指标
主要结局
Solicited and unsolicited serious adverse events
时间窗: through study completion, an average of 1 year
Safety
HIV DNA (copies/106 CD4+ T cells)
时间窗: Change from Baseline at week 28, 48
Efficacy
Frequencies of CD4+ T cells that produce Tat/Rev transcription (tat/rev RNA+ cells/106 CD4+ T cells)
时间窗: Change from Baseline at week 24, 36, 48, 60, 72
Efficacy
次要结局
- HIV-specific CD8+ and CD4+ T cells(Week 28, 48)
- ADCC(Week 28, 48)
- Unspliced and multiply-spliced RNA+ cells/1000 ng cellular RNA(Week 24, 36, 48, 60, 72)
- IUPM from total CD4+ T cells in blood by QVOA(Week 24, 36, 48, 60, 72)
- Plasma HIV RNA by SCA(Week 24, 36, 48, 60, 72)
- Binding and neutralizing Ab(Week 28, 48)
- Solicited and unsolicited non-serious adverse events(through study completion, an average of 1 year)
- Gene expression on HIV-specific CD8+ and CD4+ T cells(Week 28, 48)
- Global gene expression on PBMCs by RNA seq(Week 28, 48)