Type I Hypersensitivity Clinical Trial
Official title:
A Double Blind Study to Investigate the Clinical Efficacy and Safety of Ragweed MATAMPL (Allergy Therapeutics®), Pollinex®-R (Allergy Therapeutics®) and Placebo in Patients With Seasonal Allergic Rhinitis With Ragweed Allergy, in an Environmental Exposure Chamber (EEC) Model, With Follow-Up During a Natural Ragweed Pollen Season
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00133159 -
Different Doses of Tyrosine Adsorbed Grass Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Grass Pollen
|
Phase 2 | |
| Completed |
NCT00133146 -
Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Grass Pollen Allergy Vaccine
|
Phase 2 | |
| Terminated |
NCT00387478 -
Investigation of Efficacy and Safety of Tree MATAMPL,Tree MATA, and Placebo in Patients With Birch-Induced Seasonal Allergic Rhinitis
|
Phase 2 | |
| Completed |
NCT00414141 -
Efficacy and Safety/Tolerability of Grass MATA MPL
|
Phase 3 | |
| Completed |
NCT00258635 -
Investigation of Safety+Efficacy of Different Doses of RagweedMATAMPL;Assessment of Residual Allergenicity Using Skin Prick Test
|
Phase 2 | |
| Completed |
NCT00325338 -
Follow-up Investigation of Efficacy of Ragweed MATAMPL,and Placebo in Patients With Ragweed-induced Seasonal Allergic Rhinitis
|
Phase 2 | |
| Withdrawn |
NCT00109759 -
Evaluation of Safety and Tolerability of Tyrosine Adsorbed Ragweed Pollen Allergoid With MPL (Monophosphoryl Lipid A)
|
Phase 1 | |
| Completed |
NCT00423787 -
Efficacy and Safety/Tolerability of Ragweed MATA MPL
|
Phase 3 | |
| Completed |
NCT00104390 -
Assessment of Residual Allergenicity of Grass/Rye Pollen Allergoid Using Skin Prick Testing
|
Phase 1 | |
| Completed |
NCT00104377 -
Induction of Immunogenicity With Different Doses of Grass MATA in Subjects Allergic to Grass and Rye Pollen
|
Phase 2 | |
| Completed |
NCT00116285 -
Assessment of Residual Allergenicity of Ragweed Pollen Allergoid With Monophosphoryl Lipid A (MPL) Using Skin Prick Testing
|
Phase 1 | |
| Completed |
NCT00118612 -
Different Doses of Tyrosine Adsorbed Tree Pollen Allergoid With Monophosphoryl Lipid A (MPL) in Patients Sensitized to Tree Pollen
|
Phase 2 | |
| Completed |
NCT00113750 -
Induction of Immunogenicity With Different Doses of TreeMATA in Subjects Allergic to Tree Pollen
|
Phase 2 | |
| Completed |
NCT00118625 -
Assessment of the Contribution of Monophosphoryl Lipid A (MPL) to a Tree Pollen Allergy Vaccine
|
Phase 2 | |
| Completed |
NCT00241410 -
Safety, Immunological Effect and Efficacy of the Combined Application of MPL and Grass Pollen Allergen
|
Phase 1 | |
| Completed |
NCT00107705 -
Assessment of Residual Allergenicity of Tree (Birch, Hazel, and Alder) Pollen Allergoid Using Skin Prick Testing
|
Phase 1 |