VRC 605: Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults
Condition: HIV Prevention
Intervention: VRC-HIVMAB075-00-AB
Intervention description: VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Broadly Neutralizing; HIV Prevention; Anti-Drug Antibody; HIV-1; Immune Response

Summary:

      Background:

      Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to
      fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent
      mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat
      HIV-1 infected people.

      Objective:

      To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy
      adults.

      Eligibility:

      Healthy people ages 18-50

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and urine tests

      Participants will be assigned to 1 of 7 groups:

      Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks.

      Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48
      weeks.

      Participants will get the drug in 1 of 2 ways:

      Infusion into a vein over at least 30 minutes. Participants will have blood tests 1, 3, and 6
      hours after the infusion. They will have 1-3 visits during that week. Those in Group 7 will
      have 4-5 visits in the week after their second and third doses.

      Injection into the fatty tissue under the skin. Participants will have blood tests before the
      injection. They will have 1-3 visits during that week. Those in Group 6 will have 4-5 visits
      after the second and third doses.

      Visits include:

      Physical exam

      Blood and urine tests

      Optional oral swabs to collect saliva

      Participants will keep a diary of their temperature and symptoms for 3 days after each dose.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        A volunteer must meet all of the following criteria:

          -  Able and willing to complete the informed consent process.

          -  18 to 50 years of age.

          -  Based on history and examination, must be in good general health and without history
             of any of the conditions listed in the exclusion criteria.

          -  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.

          -  Willing to adhere to reduced risk sexual behavior during study participation.

          -  Screening laboratory values within 84 days prior to enrollment must 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.

               -  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 HIV infection by the FDA approved method of detection.

          -  Female-Specific Criteria:

               -  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 Beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum)
                  on day of enrollment for women presumed to be of reproductive potential.

        EXCLUSION CRITERIA:

        A volunteer will be excluded if one or more of the following conditions apply:

          -  Previous receipt of licensed or investigational monoclonal antibody.

          -  Weight >115 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 the study
             participation.

          -  Receipt of any investigational study agent 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.