Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Tree Pollen Allergy Vaccine

Type I Hypersensitivity Clinical Trial

Official title: A Double-Blind Phase IIa Study to Demonstrate the Contribution of MPL® to Tyrosine Adsorbed Birch + Hazel + Alder Pollen Allergoid (Tree MATA) With a Single-Blind Portion to Evaluate the Residual Allergenicity in Skin Test in Volunteers Allergic to Birch and Hazel and Alder Pollen

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypersensitivity
• Hypersensitivity, Immediate
• Type I Hypersensitivity

• NCT number: NCT00118625
• Study type: Interventional
• Source: Allergy Therapeutics
• Status: Completed
• Phase: Phase 2
• Start date: July 2005
• Completion date: September 2005