Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to Healthy Adults
Condition: Healthy Adult Immune Responses to Vaccine
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      Ebola is a virus that has infected and killed people mostly in West Africa. There is no
      treatment or prevention for it, but several drugs are being studied. Researchers want to test
      the drug MAb114 in healthy people not exposed to Ebola to see whether it can be used for
      Ebola treatment in people who are infected in the future. This trial will not expose
      volunteers to the Ebola virus.

      Objectives:

      To see if MAb114 is safe and how a person's body responds to it.

      Eligibility:

      Healthy adults ages 18-60 who weigh 220.5 pounds or less

      Design:

      Participants will be screened under protocol NIH 11-I-0164 with:

        -  Medical history

        -  Physical exam

        -  Blood or urine tests

      Participants will have a first 8- to10-hour visit. They will get MAb114 by IV infusion. For
      this, a thin tube will be placed in an arm vein. They may get an IV line in their other arm
      to collect blood. Blood will be taken many times before and after the infusion. Participants
      may have a urine test.

      Participants will get a thermometer to check their temperature for 3 days after they get
      MAb114. They will record their highest temperature and any symptoms.

      Participants will have about 14 more study visits over 6 months. At each visit, they will
      have blood taken and be checked for any health changes. They will talk about how they are
      feeling and if they have taken any medications.

      At the end of the 6 months, participants may be invited to take part in another study for
      follow-up sample collection.
    

Detailed description: 
      VRC 608: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a
      Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to
      Healthy Adults

      Study Design: VRC 608 is the first-in-human Phase I study to examine safety, tolerability and
      pharmacokinetics of the monoclonal antibody (MAb), VRC-EBOMAB092-00-AB (MAb114). MAb114 will
      be administered as a single dose. The hypotheses are: 1) MAb114 administration to healthy
      adults will be safe by the intravenous (IV) route; and 2) MAb114 will be detectable in human
      sera with a definable half-life. The primary objectives are to evaluate the safety and
      tolerability of MAb114 in healthy adults. Secondary objectives will evaluate the
      pharmacokinetics of MAb114 and the potential to detect an anti-drug antibody response to
      MAb114.

      Product Description: MAb114 is a human IgG1 MAb targeted to the Zaire ebolavirus (EBOV)
      glycoprotein (GP). It was developed by the VRC/NIAID/NIH and manufactured at Cook Pharmica
      LLC d.b.a. Catalent Indiana, LLC (Bloomington, IN) under current Good Manufacturing Practice
      (cGMP) regulations. MAb114 is supplied as a lyophilized product in a glass vial at 400 mg per
      vial with target overfill to 425 mg per vial.

      Subjects: Up to 30 healthy adults, 18-60 years of age.

      Study Plan: This is an open-label, dose-escalation study of MAb114 administered by IV
      infusion at dosages of 5, 25 and 50 mg/kg (Groups 1-3). Enrollment will begin with the lowest
      dose group. Following the first product administration in each group, the study team will
      wait at least 3 days before administering MAb114 to a second subject within the same group.
      Dose-escalation evaluations will occur to ensure the safety data support proceeding to the
      higher doses. Solicited reactogenicity following product administration will be evaluated
      using a 3-day diary. Assessment of safety will include clinical observation and monitoring of
      serum hematological and chemical parameters at defined timepoints throughout the study.

        -  Group 1: 3 subjects; 5 mg/kg IV

        -  Group 2: 5 subjects; 25 mg/kg IV

        -  Group 3: 10 subjects; 50 mg/kg IV

        -  Total* 18 subjects

             -  A minimum of 18 subjects will be enrolled. Enrollment up to a total of 30 subjects
                is permitted if additional subjects are necessary for safety or pharmacokinetic
                (PK) evaluations.

      Study Duration: Subjects will be followed for 24 weeks after the study product
      administration.
    

Intervention name(s): VRC-EBOMAB092-00-AB (MAb114)
Intervention type(s): Biological
Intervention description(s): VRC-EBOMAB092-00-AB (MAb114) is a human immunoglobulin (IgG1) monoclonal antibody (MAb) targeted to the Zaire ebolavirus (EBOV) glycoprotein (GP).
Intervention MeSH terms: Ansuvimab
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ebola Virus; Immune Response; Filovirus; Ebola Hemorrhagic Fever; First in Human