Phase I Study to Evaluate a Human Monoclonal Antibody (MAb) 10E8VLS Administered Alone or Concurrently With MAb VRC07-523LS Via Subcutaneous Injection in Healthy Adults
Condition: Healthy Adult Immune Response
Intervention: VRC-HIVMAB095-00-AB (10E8VLS); VRC-HIVMAB075-00-AB (VRC07-523LS)
Intervention description: 10E8VLS is an investigational Monoclonal Antibody targeted to the membrane proximal external region and proximal viral membrane lipid region of HIV-1.; 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: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV Prevention; Broadly Neutralizing Monoclonal Antibodies; First in Human Study; Anti-Drug Antibody Response to 10E8VLS or VRC07-523LS

Summary:

      Background:

      Human immunodeficiency virus (HIV) infection is a serious disease. There is no cure or
      vaccine to prevent infection. Using antibodies might be a good way to treat or prevent HIV.
      Antibodies are naturally made by the body to fight germs. Researchers want to test if two
      antibodies made artificially in a lab can help to prevent HIV infection. The antibodies are
      10E8VLS and VRC07-523LS.

      Objective:

      To see if 10E8VLS and VRC07-523LS are safe and well-tolerated and how long they stay in the
      blood.

      Eligibility:

      Healthy adults ages 18-60

      Design:

      Volunteers were screened in another protocol.

      Participants were enrolled in 1 of 4 groups:

      Group 1 participants were enrolled to receive 1 dose of 10E8VLS.

      Group 2 participants were enrolled to receive 3 doses of 10E8VLS.

      Group 3 participants were enrolled to receive 1 dose of both 10E8VLS and VRC07-523LS.

      Group 4 participants were enrolled to receive 3 doses of both 10E8VLS and VRC07-523LS.

      Participants in Groups 1 and 3 were expected to be enrolled about 13 visits over 24 weeks.

      Participants in Groups 2 and 4 were expected to be enrolled about 26 visits over 48 weeks.

      Participants were weighed before each dose. Women may have had a pregnancy test. Participants
      had blood collected.

      A small needle injected each dose into fatty tissue of the belly, upper arm, or thigh.
      Participants received between 1 and 8 injections per dose depending on their weight. Heavier
      participants received more injections.

      Participants received a ruler and thermometer. They checked their temperature for 3 days
      after injection(s) and measured any redness, swelling, or bruising at the injection site.

      At non-injection visits, participants had blood drawn and were checked for health changes or
      problems.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Willing and able to complete the informed consent process.

               2. 18 to 60 years of age.

               3. Based on history and examination, in good general health and without history of
                  any of the conditions listed in the exclusion criteria.

               4. Willing to have blood samples collected, stored indefinitely, and used for
                  research purposes.

               5. Able to provide proof of identity to the satisfaction of the study clinician
                  completing the enrollment process.

               6. Screening laboratory criteria within 84 days prior to enrollment must meet the
                  following criteria:

          -  White blood cell count (WBC): 2,500-12,000/mm^3.

          -  WBC differential: 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 PI or designee
             approval.

          -  Creatinine: less than or equal to 1.1 x Upper Limit of Normal (ULN).

          -  Aspartate aminotransferase (AST): less than or equal to 1.25 x ULN

          -  Alanine aminotransferase (ALT): less than or equal to 1.25 x ULN.

          -  Negative for HIV infection by an FDA approved method of detection.

          -  Negative for Hepatitis B core antibody (HBcAb) and Hepatitis C virus antibody (HCV
             Ab).

        Female-Specific Criteria:

        7. 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.

        8. 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:

               1. Woman who is breast-feeding, or planning to become pregnant during the study.

               2. Prior receipt of licensed or investigational monoclonal antibody.

               3. Weight > 115 kg.

               4. Any history of a severe allergic reaction with generalized urticaria, angioedema
                  or anaphylaxis within the 2 years prior to enrollment that has a reasonable risk
                  of recurrence during the study.

               5. Hypertension that is not well controlled.

               6. Receipt of any investigational study agent within 28 days prior to enrollment.

               7. Any other chronic or clinically significant condition that in the opinion of
                  investigator would jeopardize the safety or rights of the volunteer including
                  (but not limited to): diabetes mellitus type I/II, chronic hepatitis; OR
                  clinically significant forms of drug or alcohol abuse, asthma, autoimmune
                  disease, psychiatric disorders, heart disease, or cancer.