Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), Administered Intravenously or Subcutaneously to Healthy Adults
Condition: HIV Infection; Monoclonal Antibody, Human; HIV Antibodies; VRC01 Monoclonal Antibody; Neutralizing Antibody
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - VRC01 is a manmade antibody directed against the human immunodeficiency virus (HIV).
      Antibodies fight infection. Researchers eventually want to know if VRC01 helps prevent or
      treat HIV infection. In this study they want to know if the study drug is safe if taken in a
      vein or under the skin. Taking VRC01 in this study will not protect against HIV infection.

      Objectives:

      - To see if VRC01 and placebo are safe and well tolerated.

      Eligibility:

      - Healthy adults 18 to 50 years old.

      Design:

        -  Participants will be screened with medical history, physical exam, and lab tests.

        -  Participants will be randomly divided into 4 groups. VRC01 or the placebo will be given
           in weeks 1 and 4. Blood samples will be taken several times after each VRC01 or placebo
           dose.

        -  Three groups will receive VRC01 by needle into a vein with an IV pump. It will take
           about 1 hour and it is done in the hospital.

        -  One group will receive either VRC01 or the placebo by needle into the fatty tissue under
           the skin, usually the belly. It will take up to 20 minutes and it is done in the
           hospital.

        -  Participants will stay in the hospital overnight after receiving the medication and have
           about 14 clinic visits over 4 months. Most clinic visits last about 2 hours.

        -  Participants will keep a symptom diary after receiving the medicatino.

        -  Participants can volunteer to have mouth, rectal, and genital samples taken throughout
           the study.

        -  The study will last 8 months.
    

Detailed description: 
      Study Design: This is the first study in healthy adults of the VRC-HIVMAB060-00-AB (VRC01)
      monoclonal antibody (MAb). It is a dose-escalation study to examine safety, tolerability,
      dose, and pharmacokinetics of VRC01. The hypothesis is that VRC01 will be safe for
      administration to healthy adults by the intravenous (IV) and subcutaneous (SC) routes and
      will not elicit hypersensitivity reactions. A secondary hypothesis is that VRC01 will be
      detectable in human sera with a definable half-life. The SC route evaluation will be
      placebo-controlled and conducted double-blinded to evaluate safety and tolerability of VRC01
      and placebo (VRC-PLAMAB068-00-AB).

      Products Description: VRC-HIVMAB060-00-AB (VRC01) is a human MAb targeted to the HIV-1 CD4
      binding site. It was developed by VRC/NIAID/NIH and manufactured under cGMP by the Vaccine
      Pilot Plant (VPP) operated by Leidos Biomedical Research, Inc. (formerly SAIC-Frederick,
      Inc.), Frederick, MD. Vials are provided at 100 plus or minus 10 mg/mL in a volume of 2.25
      mL/vial.

      VRC-PLAMAB068-00-AB (placebo) is a sterile, buffered aqueous solution of 25 mM Sodium
      Citrate, 50 mM Sodium Chloride, 150 mM L-Arginine Hydrochloride, 10% Dextran 40 (w/w), and
      0.005% Polysorbate 80 (w/w) at pH 5.8. The placebo is filled at 2.25 plus or minus 0.1
      mL/vial in 3 mL glass vials.

      Subjects: Healthy adults, 18-50 years of age.

      Study Plan: There are 3 open-label, dose escalation groups (Groups 1, 2, and 3) for IV
      administration and 1 blinded, placebo-controlled group (Group 4) for SC administration.
      Enrollment will start with subject randomization to Groups 1 and 4 in a 1:2 ratio. Within
      Group 4, subjects will be randomized to SC administration of VRC01 or placebo in a 1:1 ratio.
      No more than one subject per day in each group will receive the first IV infusion of the
      study product, and no more than one subject per week will receive the first SC infusion for
      the first 6 subjects in Group 4. If a first infusion is not administered or there are
      discontinuations from the study before there are sufficient data to conduct the dose
      escalation review for a group, then extra subjects may be enrolled into that group in order
      to have the requisite data on at least 3 subjects. Safety reviews of the IV Groups will be
      conducted 2 weeks after the third subject completes the Day 0 infusion. Safety review of
      Group 4 will be conducted 2 weeks after the sixth subject completes the Day 0 infusion.

      After the IV dose escalation is complete, additional slots (up to 2 per schedule) may be
      filled in those schedules assessed as safe and well tolerated. The total accrual of 5 per
      schedule will provide additional safety and PK data to better inform product development. The
      additional enrollment slots will be filled by equal randomization of subjects to the 5 study
      schedules as they enroll. When completed with randomized enrollments, additional subjects may
      be enrolled and may receive a single VRC01 dose to evaluate the long-term pharmacokinetics.

      Subjects will be admitted to an inpatient unit and remain for 24 hours following each product
      administration. Pharmacokinetic (PK) samples will be collected with each product
      administration at baseline and at specified intervals through 28 days after each product
      administration and at 56 days after the second product administration.

      Due to the need to incur 3 days of disruption in normal daily activities that will begin with
      the first infusion, the enrollment day will most likely be different from Day 0. Safety lab
      samples will be collected at baseline, 2, 7, 14, and 28 days after each product
      administration. Subjects will keep a daily diary of solicited systemic symptoms for 3 days
      after each administration. Blood samples for human anti-VRC01 antibody evaluation will be
      drawn on Days 0, 14 and 56.

      In all groups when the subject agrees, the oral and rectal fluid samples will be obtained at
      specified intervals after each product administration; women will also be offered cervical
      fluid sample collection.

      Study Duration: The study is projected to take about 32 weeks to complete using the following
      assumptions:

        -  Individual subjects followed for 12 weeks after last VRC01 administration;

        -  All dosage groups completed;

        -  Enrollment of 3 subjects in the IV group per week during the IV dose escalation;

        -  Enrollments into Group 4 begin at the same time as Group 1.

        -  Additional subjects begin being randomized to all schedules assessed as safe and well
           tolerated beginning Week 16, and estimating 4 weeks to complete accrual and then 12
           weeks to complete follow up of the last enrolled subject.
    

Intervention name(s): VRC-HIVMAB060-00-AB
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Prevention
Keywords: Broadly HIV-1 Neutralizing Activity; Healthy Adults; Placebo; HIV Prevention; Monoclonal Antibodies; Antibodies