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
Intervention: VRC-EBOMAB092-00-AB (MAb114)
Intervention description: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Ebola Virus; Immune Response; Filovirus; Ebola Hemorrhagic Fever; First in Human

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.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        A volunteer must meet all of the following criteria:

          -  Able and willing to complete the informed consent process.

          -  Available for clinical follow-up through the last study visit.

          -  18 to 60 years of age.

          -  In good general health without clinically significant medical history.

          -  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.

          -  Physical examination without clinically significant findings within the 84 days prior
             to enrollment.

          -  Have screening laboratory values within 84 days prior to enrollment that meet the
             following criteria:

               -  White Blood Cell (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 - 400,000/mm^3

               -  Hemoglobin within institutional normal range or accompanied by the PI or designee
                  approval

               -  Creatinine less than or equal to 1.1 x upper limit of normal (ULN)

               -  Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN

               -  Negative for human immunodeficiency virus (HIV) infection by a Food and Drug
                  Administration (FDA) approved method of detection

               -  Negative for Hepatitis B core antibody (HBcAb) and Hepatitis C virus antibody
                  (HCV Ab)

          -  Criteria applicable to women of childbearing potential:

               -  If a woman is of reproductive potential and sexually active with a male partner,
                  then she agrees to use an effective means of birth control from the time of study
                  enrollment until the last study visit, or to be monogamous with a partner who has
                  had a vasectomy.

               -  Negative human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum)
                  on day of enrollment and product administration.

        EXCLUSION CRITERIA:

        A volunteer will be excluded from study participation if one or more of the following
        conditions apply:

          -  Previous receipt of a licensed or investigational monoclonal antibody or Ebola
             vaccine.

          -  Weight >100 kg.

          -  Any history of a severe allergic reaction with generalized urticaria, angioedema or
             anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the
             study.

          -  Hypertension that is not well controlled.

          -  Woman who is breast-feeding, or planning to become pregnant during study
             participation.

          -  Receipt of any investigational study product within 28 days prior to enrollment.

          -  Any other chronic or clinically significant medical condition that in the opinion of
             the 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.

          -  Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions) or significant bruising or bleeding
             difficulties with intramuscular (IM) injections or blood draws.

          -  Use of angiotensin-converting enzyme (ACE) inhibitors or other potential nephrotoxins.