Phase I, Open-Label, Dose-Escalation Study of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)
Condition: HIV Antibodies
Intervention: VRC-HIVMAB091-00-AB; rHuPH20
Intervention description: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.; Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Immune Cells; bNAb; Plasma Cell; HIV; Immunotherapy

Summary:

      Background:

      The experimental product in this study, N6LS, is a human monoclonal antibody. Antibodies are
      one way that the human body fights infection. Monoclonal means that all the antibodies in the
      product are the same. N6LS is directed against the HIV virus. There is no HIV in the N6LS
      study product and you cannot get HIV from this product. This study is the first time N6LS is
      tested in humans. It was given into a vein in the arm (intravenously, IV) or as an injection
      underneath the skin (subcutaneously, SC). The study also tested N6LS mixed with an enzyme,
      rHuPH20 (recombinant human hyaluronidase). rHuPH20 increases the spread of fluids injected
      underneath your skin (subcutaneously, SC) and allows for the rapid delivery of large volume
      injections that can be given with a single needle. It was given as a SC infusion using a
      small needle attached to an infusion pump. Study products were only given to healthy adults
      who are not infected with HIV.

      Objective:

      The main purpose of the study is to see if N6LS alone and N6LS mixed with rHuPH20 is safe in
      healthy adults. Another goal is to learn how amounts of N6LS in the body change over time.

      Study Plan:

      Assigned study groups depended on the dose of product, the numbers of times the product was
      given (once or three times at 12-week intervals), and how the product was given (IV or SC).
      Blood samples for research were collected at most of the visits. There were about 14 clinic
      visits over 6 months for all groups who got one dose of product, and about 26 clinic visits
      over 12 months for the groups who got three doses of product.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        A volunteer must have met all of the following criteria:

          1. Willing and able to complete the informed consent process.

          2. 18 to 50 years of age.

          3. Based on history and examination, must be 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 meeting 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).

               -  Alanine aminotransferase (ALT): less than or equal to 1.25 x ULN.

               -  Aspartate aminotransferase (AST): less than or equal to 1.25 x ULN.

               -  Negative for HIV infection by an FDA approved method of detection.

             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:

        A volunteer would have been excluded if one or more of the following conditions applied:

          1. Prior receipt of licensed or investigational monoclonal antibody.

          2. Weight > 115 kg.

          3. 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.

          4. Hypertension that is not well controlled.

          5. Woman who is breast-feeding, or planning to become pregnant during the study
             participation.

          6. Receipt of any investigational study agent within 28 days prior to enrollment.

          7. Any other chronic or clinically significant medical condition that in the opinion of
             investigator would jeopardize the safety or rights of the subject including (but not
             limited to): diabetes mellitus type I, chronic hepatitis; OR clinically significant
             forms of drug or alcohol abuse, asthma, autoimmune disease, infectious disease,
             psychiatric disorders, heart disease, or cancer.

          8. Known hypersensitivity to hyaluronidase or any of the excipients in ENHANZE™ Drug
             Product (EDP).