Toll-like Receptor 9 Enhancement of Antiviral Immunity in Chronic HIV-1 Infection: a Phase 1b/2a Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Part A: NK cell activation
研究概览
简要总结
Combination antiretroviral treatment (cART) effectively suppresses virus replication and partially restores immune functions. However, cART cannot cure HIV infection.
This study aim to investigate whether the antiviral immune response can be enhanced and/or viral transcription reactivated with MGN1703. MGN1703 is an agonist to toll-like receptor (TLR) 9. Activation of TLR9 has been shown to augment innate and adaptive immune effector functions, most notably enhanced NK cell and T cell functions.
Furthermore, TLR9 agonists have been shown in vitro to reactivate viral transcription in latently infected cells, potentially leading to enhanced recognition of infected cells by the immune effector cells.
详细描述
In Part A, participants will receive 4 weeks MGN1703 therapy (60 mg s.c. twice weekly). During the 4 weeks, participants will be closely monitored for safety and therapeutic effects of the drug. Targeted enrolment in Part A is 14-16 study subjects.
In Part B, participants will receive 24 weeks of MGN1703 therapy (60 mg s.c. twice weekly). During the 24 weeks, participants will be frequently monitored for safety and therapeutic effects of the drug. Targeted enrolment in Part B is 10-12 study subjects, preferentially recruited from part A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Documented HIV-1 infection
- •Age >18 years
- •CD4+ T-cell count >350/µL at screening
- •On cART (for a minimum of 12 months)
- •Able to give informed consent.
排除标准
- •Pregnancy as determined by a positive urine beta-hCG (if female)
- •Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the entire study period.
- •Currently breast-feeding (if female)
- •Viral load (HIV RNA) > 50 copies/mL
- •Contraindication to receive MGN1703 as per current investigator brochure
- •Presence of acute bacterial infection or undiagnosed febrile condition
- •Concurrent chronic systemic immune therapy or immunosuppressant medication, including continuous systemic steroid treatment within the last 2 weeks prior to randomization
- •Use of antibiotic therapy within the last 2 weeks prior to randomization
- •Known HBV or HCV infection
- •Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives (such as severe alcohol abuse, severe drug abuse, dementia)
- •Unable to follow protocol regimen
研究组 & 干预措施
MGN1703
TLR-9 agonist MGN1703 administered to HIV-1 positive patients on cART
干预措施: MGN1703 (Drug)
结局指标
主要结局
Part A: NK cell activation
时间窗: 12 weeks
As measured by CD69 expression
Part B: Quantification of the size of the HIV reservoir
时间窗: 32 weeks
As measured by quantitative viral outgrowth (qVOA) and total HIV DNA
次要结局
- Safety and tolerability, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).(12 weeks)
- The size of the HIV-1 reservoir(12 weeks)
- Viral transcription(12 weeks)