Study of Valortim® (MDX-1303) and Its Selected Formulation Components Percutaneous Use
Condition: Allergic Reactions
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine if Valortim, or one or more of its selected
      formulation components, induces a wheal reaction when introduced percutaneously.

      Two of 4 subjects dosed in a previous study with a modified formulation of Valortim
      experienced treatment related adverse events which were suggestive of allergic or
      allergic-like reactions. In order to better characterize these reactions and determine if
      they represent allergic or allergic-like reactions to Valortim or one or more of its
      components, skin testing of Valortim and selected components on naïve and Valortim-exposed
      subjects will be performed in this study
    

Detailed description: 
      A maximum of 7 subjects will participate in the study. Up to four of these subjects have been
      previously exposed to IV Valortim.

      The study will be conducted in two stages. The first stage will be performed on subjects not
      previously exposed to Valortim (Valortim-naïve subjects), to determine the correct dilutions
      of the test components. The second stage will be performed on the Valortim-exposed subjects
      using the dilutions of test components as determined in the first stage of the study.

      The following components will be tested to determine their ability to induce a wheal reaction
      shortly after exposure to the skin by percutaneous application by needle prick: Valortim
      (Lot# 10-08-001), polysorbate 80, mannitol, histamine (positive control), and saline
      (negative control). All components except histamine will be provided to the clinical site by
      PharmAthene with detailed instructions for handling, storage, and dilution. A tiny drop of
      the aforementioned components will be introduced onto the surface of the skin and the skin
      will be pricked, allowing the components to enter the surface of the skin. Multiple
      components will be tested on the subjects' forearms or back; location of testing to be
      determined by scars, moles,pre-existing skin lesions, or other issues deemed by the Principal
      Investigator (PI) to have the potential to interfere with interpretation of the results.

      Stage I:

        -  3 Valortim-naïve, non-allergic subjects

        -  Only one subject will be skin tested in a single day

        -  Subjects will be tested percutaneously with the above mentioned components at the
           following dilutions:

             -  Valortim (Lot #10-08-001, 25 mg/mL) will be filtered through a 0.22 µm syringe
                filter and diluted 1:1000, 1:100, 1:10, and 1:1 in saline.

             -  Polysorbate 80 will be diluted in saline to the following concentrations: 0.06
                mg/mL, 0.2 mg/mL, and 0.6 mg/mL.

             -  Mannitol (30 mg/mL) will be diluted in saline to the following concentrations:
                1:1000, 1:100, 1:10, and 1:1

             -  Histamine (1 mg/mL), positive control

             -  Saline (0.9%), negative control.

        -  Multiple dilutions of Valortim, polysorbate 80, and mannitol will be used to determine
           the appropriate dilution for the second stage of the study in an attempt to avoid the
           possibility of a false positive reaction due to irritation.

        -  The starting dilution for Valortim and mannitol will be 1:1000 and will move
           progressively to more concentrated dilutions (1:100, 1:10, 1:1). The starting dilution
           for polysorbate 80 will be 0.06 mg/mL and will also move progressively higher to
           concentrations of 0.2 mg/mL and 0.6 mg/mL respectively.

        -  Fifteen minutes after the application of the test articles, the skin test sites will be
           examined for a wheal reaction. The skin sites will be examined again 1 hour following
           testing, just prior to discharge from the clinic. Subjects will return at 1 and 2 days
           following testing to assess the skin testing sites and to observe for any adverse
           events.

        -  A skin test is considered positive if, at 15 minutes following application, the wheal
           produced by the test article is equal to or greater than, that caused by positive
           control (histamine), or is at least 3 mm greater than the wheal of negative control
           (saline).

        -  A negative skin test is no wheal, or a wheal less than 3 mm larger than the saline
           control as determined at 15 minutes following application.

      Stage II:

        -  It is anticipated that up to 4 subjects that received Valortim in a previous study
           (#0036-08-05) will participate in Stage II of the study; two of these subjects
           experienced adverse events while being dosed with Valortim. Subjects will each be tested
           percutaneously with Valortim, polysorbate 80, mannitol, histamine, and saline.

             -  Only one subject will be skin tested in a single day.

             -  The appropriate dilution for Valortim, mannitol, and polysorbate 80 will be based
                on the results from Stage I of this study. As was done in Stage I, Valortim will be
                filtered through a 0.22 µm syringe filter. Histamine (1 mg/mL) and saline (0.9%)
                will be used as the positive and negative controls, respectively.

        -  Fifteen minutes after the application of the test articles and pricking the skin, the
           skin test sites will be examined for a wheal reaction. The skin sites will be examined
           again 1 hour following testing, just prior to discharge from the clinic. Subjects will
           return at 1 and 2 days following testing to assess the skin testing site and to observe
           for any adverse events.

        -  A skin test is considered positive if the wheal produced by the test article 15 minutes
           following application is equal to or greater than that caused by positive control
           (histamine), or is at least 3 mm greater than the wheal of negative control (saline).

        -  A negative skin test is no wheal, or a wheal less than 3 mm larger than the saline
           control as determined at 15 minutes following application.
    

Intervention name(s): Valortim and selected Components; Valortim and Selected Components
Intervention type(s): Biological; Drug
Intervention description(s): Valortim (Lot #10-08-001, 25 mg/mL) will be filtered through a 0.22 µm syringe filter and diluted 1:1000, 1:100, 1:10, and 1:1 in saline.
Polysorbate 80 will be diluted in saline to the following concentrations: 0.06 mg/mL, 0.2 mg/mL, and 0.6 mg/mL.
Mannitol (30 mg/mL) will be diluted in saline to the following concentrations: 1:1000, 1:100, 1:10, and 1:1
Histamine (1 mg/mL), positive control
Saline (0.9%), negative control; • It is anticipated that up to 4 subjects that received Valortim in a previous study (#0036-08-05) will participate in Stage II of the study; two of these subjects experienced adverse events while being dosed with Valortim. Subjects will each be tested percutaneously with Valortim, polysorbate 80, mannitol, histamine, and saline.
Only one subject will be skin tested in a single day.
The appropriate dilution for Valortim, mannitol, and polysorbate 80 will be based on the results from Stage I of this study. As was done in Stage I, Valortim will be filtered through a 0.22 µm syringe filter. Histamine (1 mg/mL) and saline (0.9%) will be used as the positive and negative controls, respectively
Other intervention name(s): Anthrax; Anthrax
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Allergic-Like Reaction; Selected Formulation Components