Phase 1, Open-label, Single Dose Study to Examine Safety, Tolerability, Pharmacokinetics and Virologic Impact of VRC01LS or VRC07-523LS in HIV-infected Viremic Adults
Condition: HIV-1
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      The human body uses antibodies as one way to help fight infection. VRC01LS and VRC07-523LS
      are antibodies directed against the HIV virus. Researchers want to see if they are safe and
      well tolerated. In Part A of the study, the researchers studied VRC01LS. Part A of the study
      was completed in 2017. In Part B, the researchers studied VRC07-523LS. Depending on which
      antibody received, researchers studied the amount of VRC01LS or VRC07-523LS in the body and
      how it changes over time. They evaluated the effect of antibodies on CD4+ (Cluster of
      Differentiation 4) lymphocyte count and HIV viral load, and checked to see if people who get
      VRC01LS or VRC07-523LS develop an immune response to it.

      Objective:

      To see if VRC01LS and VRC07-523LS are safe and well tolerated.

      Eligibility:

      Adults ages 18-70 who are HIV infected but otherwise healthy.

      Design:

      Participants received the study drug one time by IV infusion. A needle guided a thin tube
      into a vein. The study drug mixed with salt water was dripped into the vein over about 30
      minutes.

      Participants were monitored for 30 minutes after the infusion.

      Blood samples were taken at the following times:

        -  Once before the infusion

        -  5 times in the 4 hours after the infusion

        -  1 time 24 hours after infusion. Some participants may have had 3 optional blood draws in
           the time period between 4 and 24 hours.

      For 3 days after the infusion, participants recorded their temperature and reactogenicity
      symptoms in a diary.

      There were a total of 23 study visits over 48 weeks. Ten visits were in the first 4 weeks. At
      all visits, participants answered health questions and gave blood samples.
    

Detailed description: 
      Study Design:

      Open-label, single dose study to examine safety, tolerability, pharmacokinetics and virologic
      impact of VRC01LS or VRC07-523LS in HIV-infected viremic adults.

      Study Hypotheses:

      This is the first study of VRC01LS or VRC07-523LS in HIV-infected viremic adults. The primary
      hypothesis is that both VRC01LS and VRC07-523LS will be safe for intravenous administration
      to HIV-1-infected adults. The secondary hypothesis is that VRC01LS and VRC07-523LS will be
      detectable in human sera with a definable half-life.

      Product Description:

      VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB075-00-AB (VRC07-523LS) are human monoclonal
      antibodies (MAbs) targeted to the CD4+ binding site of HIV-1. Both MAbs are modifications of
      the VRC01 MAb (which has been shown to be safe and to have antiviral activity in human
      studies) with the addition of the "LS", a 2-amino acid mutation designed to improve the
      half-life of the antibody. These MAbs were developed and manufactured by VRC/NIAID/NIH under
      current Good Manufacturing Practice (cGMP) at the VRC Vaccine Pilot Plant operated under
      contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc.,
      Frederick, MD. Vials were provided at 100 mg/mL.

      Participants:

      HIV-1-infected viremic adults; 18-70 years of age.

      Study Plan:

      This study assessed VRC01LS or VRC07-523LS administered at 40 mg/kg IV in HIV-infected
      viremic participants. Participants enrolled in one of two parts: Part A (VRC01LS) or Part B
      (VRC07-523LS). A total of 7 participants were enrolled in Part A and received VRC01LS and a
      total of 9 participants were enrolled in Part B and received VRC07-523LS. Safety lab samples,
      HIV viral load, CD4+ lymphocyte count, pharmacokinetic (PK) samples, and blood samples for
      detection of human anti-VRC01LS antibody (Part A) and human anti-VRC07-523LS antibody (Part
      B) were drawn at baseline and intervals throughout the study. Participants recorded in a
      daily diary reactogenicity symptoms for 3 days after study product administration and were
      queried at each study visit for adverse events. Participants were strongly encouraged to
      initiate 3-drug anti-retroviral therapy (ART), prescribed by their primary HIV clinician; not
      study-provided, any time after completing the day 14 study evaluations.

      VRC 607/A5378 Study Schema:

        -  Part: A; Participants: 7; Product: VRC01LS; Administration Schedule (Day 0): 40 mg/kg
           IV.

        -  Part: B; Participants: 9; Product: VRC07-523LS; Administration Schedule (Day 0): 40
           mg/kg IV.

             -  Total Participants: 16

      Study Duration:

      Participants were followed for 48 weeks after study product administration.
    

Intervention name(s): VRC-HIVMAB080-00-AB; VRC-HIVMAB075-00-AB
Intervention type(s): Biological; Biological
Intervention description(s): VRC01LS is an investigational human monoclonal antibody targeted to the CD4+ binding site of HIV-1.; VRC07-523LS is an investigational human monoclonal antibody targeted to the CD4+ binding site of HIV-1.
Other intervention name(s): VRC01LS; VRC07-523LS
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV Viral Load; Antiviral; CD4 Count; HIV-1 Infection; Broadly Neutralizing Antibody