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

National Institute of Allergy and Infectious Diseases (NIAID)1 个研究点分布在 1 个国家目标入组 49 人开始时间: 2015年11月16日最近更新: 2019年12月17日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: National Institute of Allergy and Infectious Diseases (NIAID)
入组人数: 49
试验地点: 1
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

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

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

•INCLUSION CRITERIA:
•A volunteer must meet all of the following criteria:
•Able and willing to complete the informed consent process.
•18 to 50 years of age.
•Based on history and examination, must be in general good health without history of any of the conditions listed in the

排除标准

•Willing to have blood samples collected, stored indefinitely, and used for research purposes.
•Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
•Screening laboratory values within 84 days prior to enrollment must meet the following criteria:
•WBC 2,500-12,000/mm(3).
•WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
•Platelets = 125,000 to 400,000/mm(3).
•Hemoglobin within institutional normal range.
•Creatinine less than or equal to 1.1 x ULN.
•ALT less than or equal to 1.25 x ULN.
•Negative for HIV infection by the FDA approved method of detection.
•Female-Specific Criteria:
•If a woman is secually active with a male partner and has no history of hysterectomy, tubal ligation, or menopause, then she agrees to use either a prescription birth control method or barrier birth control method from the time of study enrollment until the last study visit, or to have a monogamous partner who has had a vasectomy.
•Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.
•EXCLUSION CRITERIA:
•A volunteer will be excluded if one or more of the following conditions apply:
•Previous receipt of monoclonal antibody whether licensed or investigational.
•Weight >115 kg.
•History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of recurrence.
•Hypertension that is not well controlled.
•Woman who is breast-feeding, or planning to become pregnant during the study participation.
•Receipt of any investigational study agent within 28 days prior to enrollment.
•Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer. Including, but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.