Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Individuals With Acute HIV Infection
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety)
研究概览
简要总结
Reducing HIV persistence in lymph nodes by Interleukin-15 (IL-15) Receptor super-agonist (N-803) in Individuals with Acute HIV Infection
详细描述
This is a phase II, randomized, unblinded, controlled trial to investigate the safety, tolerability and immunomodulation effect of combining N-803 with ART during AHI. The study will be conducted at the Thai Red Cross AIDS Research Centre (TRCARC)/King Chulalongkorn Memorial Hospital and the Faculty of Medicine, Chulalongkorn University in Bangkok, Thailand.
Eligible participants will be asked to undergo LN Bx at baseline (untreated AHI), prior to initiating dolutegravir-based ART.
This study will have three steps.
In Step 1, N-803 will be administered subcutaneously at weeks 0, 3, 6 (total 3 doses) and will be initiated together with ART. Participants will be asked to undergo a second inguinal LN Bx on the opposite groin approximately at week 6 (no later than 1 week after completion of study agents). They will be followed for safety parameters at weeks 8 and 12, after which they will roll over to the RV412, WRAIR#2178 safety monitoring protocol. Step 1 duration for individual participants will be approximately 12 weeks. Step 1 has been completed as per protocol by 12 participants, 8 N-803 recipients and 4 ART only participants and study recruitment has ended.
In Step 2, participants who have completed Step 1 as per protocol and remain virologically controlled will be given a single dose of N-803 followed by ATI. The N-803 dose will be offered to all these participants regardless of initial randomization in Step 1. In Step 2, N-803 will be administered at Step 2 week 0 followed by ATI on the same day. The participants will be followed during ATI for viral rebound and monitored for the restart criteria for a maximum of 12 weeks. Participants who do not meet ART restart criteria at the end of Step 2 will proceed to RV412, WRAIR#2178 for safety follow-up.
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
盲法说明
This study is unblinded.
入排标准
- 年龄范围
- 18 Years 至 —（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
N-803
Step 1: N-803 at 6mcg/kg every 3 weeks for 3 doses plus ART (n=10) Step 2 : N-803 at 6mcg/kg at week 0 single dose (n=8), ATI after N-803 injection until week 12 (If meet criteria to restart ART, participants will go to step 3).
Step 3: ART restart (week 0 to week 12).
干预措施: N-803 (Drug)
结局指标
主要结局
Rate of occurrence of ≥ grade 3 adverse events determined to be related (Safety)
时间窗: at time of study completion at week 12
Rate of occurrence of ≥ grade 3 adverse events determined to be related
Frequency of vRNA+ and vDNA+ cells and levels of vDNA and vRNA in LNs
时间窗: At baseline (week 0) and week 6
Frequency of vRNA+ and vDNA+ cells and levels of vDNA and vRNA in LNs
Frequency, phenotype and function of CD8+ T cells and innate cells in LNs
时间窗: At baseline (week 0) and week 6
Frequency, phenotype and function of CD8+ T cells and innate cells in LNs
Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.
时间窗: viral rebound during Step 2 ATI
Time (days) from ATI to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL following ATI.
次要结局
- Frequency, phenotype and function of NK, T, B and other immune cells in LNs and blood(Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12)
- Viral load area under the curve (AUCv)(during the 4 weeks after viral rebound)
- Responses to pilot discrete choice experiment survey(Step2 wk0)
- HIV-specific antibody levels and ADCC, ADCP, ADCVI activities(Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12)
- Frequency of cells harboring HIV-1 vDNA, vRNA, intact genome and replication competent HIV-1 in PBMC(Step 1 weeks 0, 3, 6, 12; Step 2 week 0; Step 3 week 12)
- Host and viral genes by transcriptome analysis(Step 1 week 0 and 6)
- Immune activation markers in blood(Step 1 weeks 0, 3, 6, 12; Step 2 weeks 0, 2, 4, 6, 8, 10; Step 3 weeks 0, 2, 4, 6, 8, 10, 12)
- Immune activation markers in CSF(Step 1 week 0, 6; Step 2 week 0; Step 3 week 0, 12)
- Extent of cerebral inflammation in MR Spectroscopy (MRS)(Step 1 week 0, 6; Step 2 week 0; Step 3 week 0, 12)