Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Tree Pollen Allergy Vaccine
Condition: Type I Hypersensitivity
MeSH terms: Hypersensitivity; Hypersensitivity, Immediate
Study type: Interventional
Phase: Phase 2

Summary: 
      Allergen-specific immunotherapy (SIT), the administration of gradually increasing quantities
      of an allergen extract to an allergic patient, is a curative approach which directly treats
      the underlying allergic disease. Tree MATA MPL has been developed to provide pre-seasonal
      specific immunotherapy for patients with an allergy to tree pollen (hay fever).

      The tolerability and immunogenicity of Tree MATA (allergen modified with glutaraldehyde and
      adsorbed to tyrosine) with and without MPL adjuvant (monophosphoryl lipid A, extracted from a
      bacterial cell surface) is being investigated in this double-blind, randomized Phase IIa
      study in volunteers allergic to birch and hazel and alder pollen.

      Additionally, this study will assess residual allergenicity of the modified birch and hazel
      and alder pollen in the product Tree MATA MPL using skin prick testing in volunteers allergic
      to birch and hazel and alder pollen.
    

Detailed description: 
      Allergic rhinitis is a nasal inflammatory disorder initiated by an immunoglobulin-E (IgE)
      mediated hypersensitivity to allergens. When a patient is exposed to an allergen to which he
      or she is sensitive, the allergen cross-links with the IgE antibody, which is bound to the
      surface of tissue mast cells. This cross-linking then triggers the release of proinflammatory
      substances, such as histamine and eicosanoids, and is known as the early response. In a skin
      prick test, this reaction produces a wheal-and-flare response. Normally, systemic exposure to
      an allergen also leads to the more prolonged late reaction, in which eosinophils, basophils,
      and activated T cells are recruited to the site of exposure. The recruited T cells also
      secrete inflammatory cytokines, such as interleukin-4 (IL-4) and IL-5, typically associated
      with helper T cells type 2 (TH2), which further propagate the inflammatory cascade.
      Typically, the early response occurs within 15 to 30 minutes (but as quickly as a few
      seconds) and usually resolves within 1 to 3 hours, and the late response occurs within 6 to
      12 hours and resolves in 24 hours.

      Allergic vaccination (AV), also referred to as immunotherapy or allergen-specific
      immunotherapy (SIT), is a curative approach that is available for allergic diseases, which
      directly treats the underlying disease. AV is the practice of administering gradually
      increasing quantities of an allergen extract to an allergic patient to ameliorate the
      symptoms associated with the subsequent exposure to the causative allergen. AV is believed to
      exert its beneficial effects on the immune system, at least in part, by modifying the
      T-lymphocyte response to subsequent natural allergen exposure. AV has been shown to inhibit
      both early and late responses to allergen exposure. AV acts on T cells to modify peripheral
      and mucosal TH2 responses to an allergen in favor of helper T cell type 1 (TH1) responses.
      One of the hallmarks of successful AV is the redressing of a "healthy" TH1/TH2-balance.

      Although efficacious, immunotherapy is generally considered a long-term disease modifying
      measure that requires months to years of treatment, entails multiple injection regimens and
      involves some risk for adverse immune reactions.

      Allergy Therapeutics (AT) has developed formulations over the years to increase both the
      safety and efficacy of such treatment. In particular, the allergen extract has been
      chemically modified with glutaraldehyde and formulated with L-tyrosine to act as a depot
      adjuvant and provide a slow release of the allergens or modified allergens. This increases
      the safety profile and enhances the efficacy-associated immunological changes. Efficacy could
      be further improved by adding the immunological adjuvant monophosphoryl lipid A (MPL).

      Tree MATA MPL is designed to provide a vaccine that will be efficacious with only three
      escalating dose injections, in contrast to the longer schedules currently in use. It is
      designed to have all of the current advantages of an allergy vaccine, which can modify the
      underlying disease process, as opposed to pharmacological control, which treats only the
      symptoms. The vaccine will also be safer to use than a formulation containing a similar mass
      of unmodified allergen extract due to the propensity of the unmodified allergen extract to
      cause severe local allergic reactions or anaphylaxis, because of its reduced reactivity with
      IgE antibody.

      The tolerability and immunogenicity of Tree MATA with and without MPL adjuvant is being
      investigated in this double-blind, randomized Phase IIa study in volunteers allergic to birch
      and hazel and alder pollen.

      Additionally, this study will assess residual allergenicity of the modified birch and hazel
      and alder pollen in the product Tree MATA MPL using skin prick testing in volunteers allergic
      to birch and hazel and alder pollen.
    

Intervention name(s): Tree MATA MPL
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Allergy; Specific Immunotherapy; Adjuvant; Allergy Vaccination; Allergenicity