Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to Healthy Adults
Condition: Prevention of HIV Infection; HIV Antibodies; Monoclonal Antibody, Human; Neutralizing Antibody
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.

      Study Duration: Subjects will be followed for 24 weeks after the last study product
      administration.
    

Intervention name(s): VRC-HIVMAB080-00-AB (VRC01LS); VRC-HIVMAB060-00-AB (VRC01)
Intervention type(s): Biological; Biological
Intervention description(s): VRC01LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.; VRC01 is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Dose Escalation; HIV Prevention; Broadly HIV-1 Neutralizing Activity; Open-Label; Half-Life