A Phase 1 Dose-escalation Study of the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Bispecific Antibody 10E8.4/iMab in HIV-1-infected and Uninfected Individuals
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 3
- 主要终点
- Safety of the highest single intravenous dose of 10E8.4/iMab in HIV uninfected individuals. Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals
研究概览
简要总结
Many HIV-infected individuals mount a broad neutralizing serologic response 2-3 years after infection. Broadly neutralizing antibodies might play an important role in protection from acquisition of HIV infection because they can protect macaques from infection, and the presence of anti-HIV antibodies was the only positive correlate of protection in an HIV vaccine efficacy trial (RV144 trial). HIV neutralizing antibodies also have the potential to alter the course of HIV infection in humans. Therefore, these antibodies might be useful to both prevent and treat HIV-1 infection.
This is a phase 1 dose escalating clinical trial to evaluate the safety, tolerability, pharmacokinetics and the antiretroviral effects of a novel bispecific monoclonal antibody 10E8.4/iMab in HIV-infected and HIV-uninfected individuals. The study will be conducted as a multi-center study at the Columbia University Medical Center in New York City and the Orlando Immunology Center in Orlando, Florida.
详细描述
There are 4 study Arms as it is possible that pharmacokinetics (PK) may differ between HIV-1-uninfected individuals (Arms 1, 2 and 4) and HIV-1-infected and viremic individuals (Arm 3). Safety and tolerability as well as PK may differ between the IV and SC routes, Arms 1, 2 and 4.
A dose escalation design has been used to establish safety and tolerability at very low doses of 10E8.4/iMab as this is a first in man study. Once demonstrated, dose levels would be increased to dosing levels thought to be more clinically relevant.
The numbers of subjects receiving active antibody in each study arm are relatively balanced such that an initial evaluation of the primary endpoint with additional dosing to provide insights into both PK and antiviral activity as well as some exploratory endpoints such as immunogenicity will be possible.
This study is a phase 1 clinical trial to evaluate the safety and tolerability, pharmacokinetics and the antiretroviral activity of the bispecific monoclonal antibody 10E8.4/iMab in HIV-infected and HIV-uninfected individuals.
HIV uninfected, healthy volunteers will be administered either one intravenous infusion of 10E8.4/iMab at one of five increasing dose levels (0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg) or one SC injection of 1 mg/kg, 2.5 mg/kg or 10 mg/kg or placebo and will be followed for 24 weeks after 10E8.4/iMab administration. HIV-infected volunteers will be administered one intravenous infusion of 10E8.4/iMab at one of three increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg).
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Participants in SC dosing Arm 4 Groups J and K will be blinded as will providers and members of the study site team. Study pharmacists will not be blinded. Safety monitoring committee will not be blinded. All participants treated IV and participants treated 1 mg/kg SC will not be masked (open-label).
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Safety of the highest single intravenous dose of 10E8.4/iMab in HIV uninfected individuals. Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals
时间窗: 24 weeks
Percentage of subjects experiencing a dose limiting toxicity defined as a Grade 3 or 4 adverse events as per the toxicity grading scale for healthy volunteers enrolled in preventative vaccine trials
Safety of the highest single intravenous dose of 10E8.4/iMab in HIV infected individuals Safety of a single dose of intravenous dose of 10E8.4/iMab in HIV uninfected individuals
时间窗: 24 weeks
Percentage of subjects experiencing a dose limiting toxicity defined as a Grade 3 or more adverse event as per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events v 2.1
Injection site reactions associated with a single subcutaneous injection of 10 E8.4/iMab in HIV uninfected individuals
时间窗: 24 weeks
Percentage of injections associated with a Grade 2 or greater injection site reaction as per the toxicity grading scale for healthy volunteers enrolled in preventative vaccine trials
Systemic infusion reaction associated with the intravenous administration of any dose of 10E8.4/iMab
时间窗: 24 weeks
Percentage of subjects receiving intravenous 10E8.4/iMab as per CTCAE version 5.0.
次要结局
- Serum levels 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals(7 days)
- Antiviral activity of the highest single dose of 10E8.4/iMab given intravenously to viremic HIV infected individuals(28 days)
- Serum levels of 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals(14 days)
- Serum levels of 10E8.4/iMab after the highest single dose of 10E8..4/iMab given subcutaneously to HIV uninfected individuals(56 days)
- Serum levels of 10E8.4/iMab after the highest single dose of 10E8.4/iMab given intravenously to HIV infected and uninfected individuals.(56 days)
- Percentage of subjects developing antibodies to 10E8.4/iMab after any single intravenous or subcutaneous dose of 10E8.4/iMab(84 days)
研究者
David Ho
Professor of Medicine
Columbia University