VRC 606: A Phase 1, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB060-00-AB (VRC01), Administered Intravenously or Subcutaneously to Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 2
- 主要终点
- Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered as a single dose at 5 mg/kg IV,20 mg/kg IV,40 mg/kg IV, and 5 mg/kg SC to healthy adults
研究概览
简要总结
Background:
Antibodies help the body fight infection. VRC01LS is an antibody directed against HIV virus. HIV attacks the immune system. In animals, VRC01LS inactivated many types of HIV viruses. Researchers want to see if it does this in people.
Objectives:
To see if VRC01LS is safe and well-tolerated in people. To see what level of VRC01LS is maintained in people and if they develop an immune response to it.
Eligibility:
Healthy people ages 18 to 50
Design:
Participants will be screened in protocol number VRC 500 (NIH 11-I-0164) with medical history, physical exam, and blood and urine tests.
The study will last 24 to 48 weeks. Visits will last 2 to 8 hours.
Participants will get VRC01LS through either:
- A needle in an arm vein or
- A small needle placed into the fatty tissue under the skin of the abdomen, thigh, or arm.
Participants will be assigned to 1 of 6 groups.
Groups 1 to 4 will get 1 dose of VRC01LS. They will have follow-up visits through week 24.
Groups 5 and 6 will get 1 dose of VRC01LS every 12 weeks (3 doses). They will have 4 to 5 visits between the second and third dose, and follow-up visits through week 48.
Participants will have 1 to 3 follow-up visits in the week after receiving VRC01LS. They will record their temperature and keep a diary of symptoms for 3 days after a dose. They may have additional unscheduled visits.
At each visit, participants will have a physical exam and may have blood and urine tests.
详细描述
VRC 606: A Phase 1, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), and VRC-HIVMAB060-00-AB (VRC01), Administered Intravenously or Subcutaneously to Healthy Adults.
Study Design: This is the first study of the VRC-HIVMAB080-00-AB (VRC01LS) monoclonal antibody (MAb) in healthy adults. It is a dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics of VRC01LS. The hypothesis is that VRC01LS will be safe to administer to healthy adults by the intravenous (IV) and subcutaneous (SC) routes. The secondary hypothesis is that VRC01LS will be detectable in human sera with a definable half-life. With protocol amendment, Group 7 and Group 8 were added to the protocol Version 2.0 to evaluate VRC01 and VRC01LS safety and pharmacokinetics in the same study.
Product Description: VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB060-00-AB (VRC01) are human MAb targeted to the CD4 binding site of HIV-1. VRC01LS is a modification of the VRC01 MAb (which has been shown to be safe in human studies) with the addition of the LS , 2-amino acid mutation designed to improve the half-life of the antibody. VRC01LS and VRC01 were developed by VRC/NIAID/NIH and manufactured under cGMP at the VRC Pilot Plan operated under contract by the Vaccine Clinical Material Program operated for NIAID/VRC by Leidos Biomedical Research, Inc., Frederick, MD. Vials are provided at 100 mg/mL.
Subjects: Healthy adults, 18-50 years of age.
Study Plan: There are 4 open-label, dose escalation groups (Groups 1-4) to assess VRC01LS administered IV and SC once per subject. 2 open-label groups (Groups 5 and 6) to assess VRC01LS at 5 mg/kg SC or at 20 mg/kg IV administered every 12 weeks for a total of 3 administrations per subject, and 2 open-label groups (Groups 7 and 8) to assess VRC01 at 5 mg/kg SC or at 20 mg/kg IV administered every 4 weeks for a total of 2 administrations per subject. Subjects will be randomized into Group 1 or Group 2 at a 1:1 ratio, or directly enrolled into Groups 3-6 per the dose escalation and safety evaluation plan. Enrollments into Group 7 and Group 8 will be randomized at a 1:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 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
Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered as a single dose at 5 mg/kg IV,20 mg/kg IV,40 mg/kg IV, and 5 mg/kg SC to healthy adults
时间窗: Through 24 weeks of study participation.
Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered at 20 mg/kg IV by repeat dosing every 12 weeks for a total of 3 infusions to healthy adults.
时间窗: Through 48 weeks of study participation.
Evaluate the safety and tolerability of VRC-HIVMAB080-00-AB administered at 5 mg/kg SC by repeat dosing every 12 weeks for a total of 3 injections to healthy adults.
时间窗: Through 48 weeks of study participation.
次要结局
- To evaluate the pharmacokinetics of VRC-HIVMAB080-00-AB at each dose level.(Through 24 weeks after the last dose.)
- To determine whether anti-drug antibody (ADA) to VRC01LS can bedetected in recipients of VRC-HIVMAB080-00-AB.(Through 24 weeks after the last dose.)