Investigation of Efficacy and Safety of Ragweed MATAMPL, Pollinex-R and Placebo in Patients With Ragweed Allergy
Condition: Type I Hypersensitivity
MeSH terms: Hypersensitivity; Hypersensitivity, Immediate
Study type: Interventional
Phase: Phase 2

Summary: 
      Ragweed MATAMPL has been developed to provide pre-seasonal specific immunotherapy for
      patients with hypersensitivity to ragweed pollen (hay fever). This novel formulation is
      designed to provide a vaccine that will be efficacious with only four escalating dose
      injections administered before the start of the pollen season.

      In this study, the safety and efficacy of Ragweed MATAMPL will be assessed by exposing
      allergic subjects to Ragweed pollen in an environmental exposure chamber (EEC). Patient
      symptomatic response to pollen and patient quality of life in the EEC will be determined.
    

Detailed description: 
      Allergic rhinitis is a nasal inflammatory disorder initiated by an immunoglobulin-E (IgE)
      mediated hypersensitivity to allergens. This condition is characterized by sneezing,
      rhinorrhea, nasal itching and congestion. When a patient is exposed to an allergen to which
      they are sensitive, the allergen cross-links with the Ig E 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 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.

      Recent improvements, such as optimal dosing, allergen modification (to reduce allergenicity
      while maintaining immunogenicity), adjuvant adsorption (to control release) and adjuvant
      activity (to assist immunomodulatory action) are being explored to reduce the risk of
      anaphylaxis and decrease the commitment to multiple injections.

      A novel allergy vaccine (Ragweed MATAMPL) has been developed for the prevention or relief of
      allergic symptoms caused by a variety of pollens. Ragweed MATAMPL, which contains the
      allergens of ragweed (chemically modified by glutaraldehyde) adsorbed onto L-tyrosine with
      the addition of the adjuvant monophosphoryl lipid A (MPL), is being evaluated for the
      specific treatment of ragweed seasonally induced allergic rhinitis. Ragweed MATAMPL is
      intended for use as a pre-seasonal therapeutic allergy vaccine in patients with proven
      seasonal allergic rhinitis and conjunctivitis due to IgE mediated allergy to ragweed. This
      novel vaccine formulation is designed to provide a vaccine that will be efficacious with only
      four escalating dose injections, in contrast to the longer schedules currently in use.

      This placebo-controlled clinical trial is designed to evaluate the safety and efficacy of
      Ragweed MATAMPL as determined by patient symptomatic response to pollen and patient quality
      of life in an environmental exposure chamber (EEC) that reproduces the clinical setting. The
      development of the EEC, which delivers a controlled pollen challenge over time and allows
      evaluation of a patient's response at any time point throughout the challenge process,
      provides the opportunity to examine various aspects of efficacy of anti-allergic treatments
      within a single center at various times of the year. The EEC affords a more controlled
      environment than natural pollen exposure in which variables such as unpredictable pollen
      levels, varying weather conditions during the study period, and varying levels of pollen
      exposure within the patient population are eliminated. Furthermore, the question of patient
      compliance is largely eliminated because the patients are scrutinized closely while they are
      recording symptoms. In addition, an EEC study is an acceptable study model for determining
      the dose response for an allergic rhinitis drug as outlined in the draft U.S. Food and Drug
      Administration (FDA) guidelines "Allergic Rhinitis Clinical Development Programs for Drug
      Products," April 2000.
    

Intervention name(s): Ragweed MATAMPL
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Allergy; Specific Immunotherapy; Ragweed; Environmental Exposure Chamber