VRC 605: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 2
- 主要终点
- Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration
研究概览
简要总结
Background:
Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat HIV-1 infected people.
Objective:
To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy adults.
Eligibility:
Healthy people ages 18-50
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Participants will be assigned to 1 of 7 groups:
Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks.
Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48 weeks.
Participants will get the drug in 1 of 2 ways:
Infusion into a vein over at least 30 minutes. Participants will have blood tests 1, 3, and 6 hours after the infusion. They will have 1-3 visits during that week. Those in Group 7 will have 4-5 visits in the week after their second and third doses.
Injection into the fatty tissue under the skin. Participants will have blood tests before the injection. They will have 1-3 visits during that week. Those in Group 6 will have 4-5 visits after the second and third doses.
Visits include:
Physical exam
Blood and urine tests
Optional oral swabs to collect saliva
Participants will keep a diary of their temperature and symptoms for 3 days after each dose.
详细描述
This is the first study of the VRC-HIVMAB075-00-AB (VRC07-523LS) monoclonal antibody (MAb) in healthy adults. It is a phase 1, dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics of VRC07-523LS. The hypothesis is that VRC07-523LS will be safe for administration to healthy adults by the intravenous (IV) and subcutaneous (SC) routes.
Healthy adults 18-50 years of age will be enrolled. There are 4 open-label, dose escalations of VRC07-523LS from 1 mg/kg IV to 40 mg/kg IV, 1 route escalation from IV to SC, and 2 open-label groups to assess repeat dosing. Groups 1-5 are expected to include 3 subjects and Groups 6-7 are expected to enroll 5 subjects. Subjects will be followed for 24 weeks after the last study product administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration
时间窗: 3 days after each product administration
Subjects recorded 3-day systemic symptoms in a diary after each study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, temperature and joint pain. Subjects recorded highest measured temperature daily. Clinicians reviewed the diary with the subject and collected resolution information for any symptoms that were not resolved within 3 days. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration
时间窗: 7 days after each product administration
Local symptoms assessed and recorded by the clinicians. Solicited local symptoms include pain/tenderness, swelling, redness, bruising, and pruritus (itchiness) at the product administration site. Clinicians assessed the study product administration site for local symptoms on the day of product administration after completion of the administration and on Days 1, 2 and 7 post administration. Subjects were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. If symptoms were experienced, clinicians collected resolution information for any symptom that was not resolved within 7 days. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Solicited reactogenicity recorded without an attribution assessment. If symptoms were reported, grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.
Number of Subjects Reporting Serious Adverse Events
时间窗: Through 24 weeks after the last product administration
Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the last product administration.
Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events
时间窗: Through 24 weeks after the last product administration
Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 56 days after the last product administration. After the indicated time period through the last expected study visit at 24 weeks after the last product administration, only new chronic medical conditions collected as unsolicited AEs. The number reported is the number of subjects who experienced at least one AE in the reporting period. A subject with multiple experiences of the same event is counted once using the event of worst severity.
次要结局
- Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Multiple Dose Groups(Through 24 weeks after the last product administration)
- Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS(Through 24 weeks after the last product administration for Groups 1-5 and through 8 weeks after the last product administration for Groups 6 and 7)
- 4 Week Mean Serum Concentration of VRC07-523LS(Week 4 post product administration)
- 12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups(Week 12 post product administration)
- Area Under the Curve (AUC(0-inf)): Single Dose Groups(Administration (0h) to 24 weeks post product administration)
- Area Under the Curve (AUC0-84D): Multiple Dose Groups(Administration (0h) up to 84 days after each product administration)
- Number of Single Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS(Weeks 4 and 8 post product administration)
- Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups(Up to 24 weeks post product administration)
- Number of Multiple Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS(Weeks 4, 28 and 32 after the first product administration)
- VRC07-523LS Clearance Rate(Administration (0h) to 28 days post product administration)
- 12 Week Mean Serum Concentration of VRC07-523LS: Multiple Dose Groups(Up to 12 weeks after each product administration)
- Overall IV Half-life (T1/2) of VRC07-523LS(Administration (0h) to 56 days post product administration)