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
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Study Design:

      This is the first study in healthy adults of the N6LS monoclonal antibody (MAb). It was a
      dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics (PK) of
      N6LS administered intravenously (IV) and subcutaneously (SC) to healthy adults. For SC
      administration, N6LS was administered alone or co-administered with the permeation enhancer
      rHuPH20 enzyme. Primary hypotheses are that N6LS administration to healthy adults will be
      safe by the IV and SC routes, alone and with rHuPH20 co-administration. A secondary
      hypothesis is that all N6LS administrations will be detectable in human sera with a definable
      half-life

      Product Description:

      N6LS (VRC-HIVMAB091-00-AB) is a human MAb targeted to the HIV-1 CD4 binding site. It was
      developed by the VRC/NIAID/NIH and manufactured under current Good Manufacturing Practice
      (cGMP) regulations at the VRC Vaccine Pilot Plant operated under contract by the Vaccine
      Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. The
      product was provided as a sterile aqueous buffered solution in 10 mL glass vials at a
      concentration of 100 mg/mL and volume of 6.25 mL.

      Each vial of ENHANZE™ Drug Product (EDP) contains 0.5 mL of rHuPH20 formulated at a
      concentration of 1 mg/mL (approximately 110,000 U/mL rHuPH20). rHuPH20 is a tissue
      permeability modifier that depolymerizes hyaluronan (HA), increasing the dispersion of a
      substance into the subcutaneous space, which enables SC delivery of co-administered antibody
      (-ies) at higher dose volumes (e.g., >10 mL) that cannot be administered quickly without
      rHuPH20. EDP is manufactured by Ajinomoto Althea, Inc. (San Diego, CA) for Halozyme
      Therapeutics, Inc. (San Diego, CA) and is supplied in 2 mL glass vials as a sterile,
      single-dose, injectable liquid.

      Subjects:

      Healthy adults, 18-50 years of age.

      Study Plan:

      This open-label study included 8 dose groups to assess N6LS alone given as a single IV
      infusion at the 5, 20, or 40 mg/kg dose level (Groups 1,3 and 4); a single SC injection at
      the 5 mg/kg dose level (Group 2); or in 3 administrations, spaced 12 weeks apart by SC
      injection at the 5 mg/kg dose level (Group 5), or by IV infusion at the 20 mg/kg dose level
      (Group 6). Two additional groups assessed N6LS given as a single SC injection mixed with
      rHuPH20 (2000 U/mL) at 5 mg/kg (Group 7) or 20 mg/kg (Group 8) doses. Enrollment opened with
      Groups 1, 2 and 5; and was followed by the sequential activation of Groups 3, 4, and 6. With
      implementation of the two SC N6LS+rHuPH20 arms as a protocol amendment, Group 7 opened first
      to accrual, followed by Group 8.

      Study Duration:

      Study participation was approximately 24 weeks for participants in Groups 1-4, 7 and 8; and
      48 weeks for participants in Groups 5 and 6.
    

Intervention name(s): VRC-HIVMAB091-00-AB; rHuPH20
Intervention type(s): Biological; Biological
Intervention description(s): 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.
Other intervention name(s): EDP
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immune Cells; bNAb; Plasma Cell; HIV; Immunotherapy