Clinical trial NCT00423787: Efficacy and Safety/Tolerability of Ragweed MATA MPL
Official title: Efficacy and Safety/Tolerability of Ragweed MATA MPL, a Randomized, Placebo-Controlled, Double-Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type I Hypersensitivity
Keywords: Allergy
Allergoid
Specific Immunotherapy
Lead sponsor: Allergy Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-01-18
Enrollment: 993
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Ragweed MATAMPL has been developed by Allergy Therapeutics to provide pre-seasonal specific immunotherapy for patients with proven type I hypersensitivity to cross reacting ragweed pollens causing rhinitis and/or conjunctivitis with or without mild to moderate asthma bronchiale. The purpose of this study is to compare the efficacy of Ragweed MATAMPL versus placebo in ragweed-allergic subjects following 4 subcutaneous injections of study medication administered before the start of the 2007 ragweed pollen season

Detailed description: Ragweed MATAMPL has been developed by Allergy Therapeutics to provide pre-seasonal specific immunotherapy for patients with proven type I hypersensitivity to cross reacting ragweed pollens causing rhinitis and/or conjunctivitis with or without mild to moderate asthma bronchiale.

An earlier formulation of Ragweed MATAMPL developed by Allergy Therapeutics (UK), Ltd, available commercially in Canada since the 1980's, is 'Pollinex®-R'. 'Pollinex®-R' is formulated with modified allergens (allergoids) of ragweed pollen extract adsorbed onto L tyrosine at 4% w/v. Related formulations developed by ATL, available commercially in selected European countries since the 1970´s on a Named Patient Basis, are 'Pollinex Tree', 'Pollinex Grass', 'Pollinex Quattro Trees' (previously known as MATA tree + MPL), and 'Pollinex Quattro Grass' (previously known as MATA grass + MPL).

Ragweed MATAMPL contains an extract of ragweed pollens. This extract is chemically modified with glutaraldehyde to produce the active ingredient, an allergoid. Such modification reduces the reactivity of the extract with IgE antibody. However, a simultaneous reduction in other important immunological properties, such as IgG and T cell reactivity is not seen. The modified extract is adsorbed to L-tyrosine as a depot formulation. MPL®, a purified, detoxified glycolipid derived from the cell walls of Salmonella minnesota, is also included in the current product formulation. This excipient/adjuvant is included to increase the immunogenic effect of the product and to enhance the switch from an allergen-specific TH2 to TH1-like T cell profile.

The current formulation is designed to provide a product that will be efficacious with only 4 injections, in contrast to the longer schedules currently in use with unmodified extracts. The product will also be safer to use than a formulation containing a similar mass of unmodified allergen extract as regards its ability to cause severe local allergic reactions or anaphylaxis, because of its reduced reactivity with IgE antibody. The modification is greater than 75%, so that only a small amount of unmodified allergen is remaining in the product.

The purpose of this study is to compare the efficacy of Ragweed MATAMPL versus placebo in ragweed-allergic subjects following 4 subcutaneous injections of study medication administered before the start of the 2007 ragweed pollen season.

Eligibility criteria: Inclusion Criteria:

* Have given written informed consent;
* Are 18 to 59 years of age;
* history of moderate to severe symptoms of seasonal allergic rhinitis and/or conjunctivitis ascribed to ragweed pollen exposure that required repeated use of antihistamines, nasal steroids, and/or leukotriene modifiers;
* history of moderate to severe symptoms in the past ragweed pollen season;
* positive skin prick test to ragweed pollen and a positive RAST or equivalent test to ragweed pollen;
* positive skin prick test to histamine;
* negative skin prick test to the negative control;
* forced expiratory volume in 1 second (FEV1) ≥ 80% of predicted, with a FEV1/FVC ratio ≥ 70%;
* Women of childbearing potential must be using a medically acceptable method of birth control;
* able to understand and comply with study instructions;
* Demonstrate proper use of electronic diary with at least 85% compliance during the 1-week period between Visit 1 and Visit 2.

Exclusion Criteria:

* pregnant or lactating
* asthma requiring the daily use of controller medication;
* emergency room visit or admission for asthma in the 12 months prior to Visit 1;
* presence of secondary alteration at the affected organ (i.e., emphysema, bronchiectasis, nasal polyps, chronic sinusitis);
* auto-immune disease;
* acute or subacute (historic) atopic dermatitis, chronic dermatitis, urticaria factitia, and/or urticaria due to physical/chemical influence or any other skin conditions which might interfere with the interpretation of the skin prick test results;
* history or presence of diabetes, cancer or concomitant illness that, in the opinion of the Investigator, would pose a safety risk or compromise the interpretation of efficacy for this ragweed immunotherapy;
* history of angioedema;
* manifest pulmonary or cardiac insufficiency;
* current malignant disease;
* disorders of tyrosine metabolism (i.e., alcaptonuria, tyrosinemia);
* acute or chronic infection;
* any clinically significant abnormal laboratory value at Visit 1;
* Perennial Allergens: positive skin prick test at Visit 1 to: house dust mites, molds, or epithelia. In these cases, a careful history is to be taken and if moderate or severe symptoms are reported when exposed to the aforementioned allergens, the subject is to be excluded. Exception: the source of the allergen (cat, dog, horse) can be avoided for the entire study.
* Springtime Flowering Plant Allergens: positive skin prick test at Visit 1 to birch, oak, sycamore, ash, red maple, black walnut, American elm, or poplar. In these cases, a careful history is to be taken and if moderate to severe symptoms are reported when exposed to the aforementioned allergens the subject is to be excluded. Exception: one or all of the listed allergens must not be tested if they are not common to the Investigator's region or, if common to the region, the treatment phase of the study can be initiated at least 30 days after the end of the allergen(s) season or treatment can be completed 30 days before the anticipated start of the allergen(s) season.
* Summertime Flowering Plant Allergens: positive skin prick test at Visit 1 to grass pollen mix or Bermuda grass. In these cases, a careful history is to be taken and if moderate to severe symptoms are reported when exposed to the aforementioned allergens the subject is to be excluded. Exception: No testing is required if there is no overlap between grass / Bermuda grass and ragweed season and if treatment can be completed 30 days before the start of grass / Bermuda grass season. Bermuda grass must not be tested if it is not common to the Investigator's region.
* Late Summer/Autumn Flowering Plant Allergens: positive skin prick test at Visit 1 to: goosefoot/lamb's quarters, firebush/kochia, or English plantain. In these cases, a careful history is to be taken and if moderate to severe symptoms are reported when exposed to the aforementioned allergens the subject is to be excluded. Exception: some or all of the listed allergens must not be tested if they are not common to the Investigator's region.
* Have inadequate washout period prior to screening (Visit 1). The following washout periods prior to Visit 1 are acceptable:

  * Oral or parenteral corticosteroids (1 month)
  * Inhaled, ocular or intranasal corticosteroids (1 day)
  * Mast cell stabilizers (7 days)
  * Intranasal or systemic decongestants including cold preparations (1 day)
  * Leukotriene modifiers (7 days)
  * Afrin (oxymetazoline hydrochloride) (14 days)
  * Antihistamines
* Once-daily or twice-daily antihistamines (7 days)
* Short-acting 3 or 4 times a day antihistamines (3 days)
* Hydroxyzine (14 days)

  * H2-blockers (1 day)
  * Other anti-inflammatory, anti-allergy, and any other medications which, in the opinion of the Investigator, may interfere with the study objectives should be considered on a case-by-case basis
  * Topical skin medications on the forearms (14 days);
* Require use of beta blockers;
* Are unable to receive epinephrine therapy (i.e., use of epinephrine is contraindicated);
* Have a history of anaphylactic reactions to foods, insect venom, exercise, or drugs;
* Have been treated with a preparation containing MPL® within 6 months prior to Visit 1;
* Have diseases with a pathogenesis interfering with the immune response, and who have received medication which could interfere with the results of the study;
* Have a history of allergy, hypersensitivity or intolerance to the excipients of the study medication;
* Have a history of allergy, hypersensitivity or intolerance to study relief medication;
* Have already undergone hyposensitisation therapy with comparable allergen extracts; An exception will be allowed if prior immunotherapy with comparable allergen was successful, symptoms reappeared some time after stopping the immunotherapy, and the immunotherapy was completed ≥ 3 years before Visit 1;
* Have participated in a clinical research trial with a new chemical substance within 4 weeks of Visit 1;
* Are unable or unwilling to cooperate with the Investigator and to comply with the protocol requirements, or not likely to complete the observation periods sufficiently;
* Have changed residence between geographical regions within the past 3 months

Primary outcomes:
measure: Compare the efficacy of Ragweed MATA MPL versus placebo as measured by the combined allergy symptom (eyes and nose)+ medication scores self-reported by subjects during the 3 peak weeks of the 2007 ragweed pollen season.
timeFrame: 9 months
Secondary outcomes:
measure: Combined symptom + medication scores, Combined symptoms, Individual symptoms, Relief medication use, Specific immunological changes, quality of life, Health Assessments, Days absent from activities
timeFrame: 9 months
measure: Adverse events, adverse reactions, clinical labs, ECG, and vitals
timeFrame: 9 months
Other outcomes:
Locations:
city: Waterbury
country: United States
facility: The Centre for Allergy, Asthma & Immunology
state: Connecticut
city: Atlanta
country: United States
facility: Allergy & Asthma Consultants
state: Georgia
city: Atlanta
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Conyers
country: United States
facility: DataQuest Medical Research
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Research Center LLC
state: Georgia
city: Lilburn
country: United States
facility: Allergy and Consultants, PC
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Chicago
country: United States
facility: University Consultants in Allergy/Immunlogy
state: Illinois
city: Normal
country: United States
facility: Sneeze, Wheeze and Itch Associates, LLC
state: Illinois
city: Iowa City
country: United States
facility: Iowa Clinical Research Corporation
state: Iowa
city: Overland
country: United States
facility: Kansas City Allergy & Asthma
state: Kansas
city: Gardner
country: United States
facility: Allergy & Arthritis Treatment Centre
state: Massachusetts
city: Ypsilanti
country: United States
facility: Respiratory Medical Research Institute of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute
state: Minnesota
city: Plymouth
country: United States
facility: Clinical Research Institute/West Health Building
state: Minnesota
city: St. Louis
country: United States
facility: The Clinical Research Center, LLC
state: Missouri
city: Omaha
country: United States
facility: Midwest Allergy and Asthma Clinic
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center Division of Allergy, Asthma and Immunology
state: Nebraska
city: Papillion
country: United States
facility: The Asthma and Allergy Centre
state: Nebraska
city: Ocean
country: United States
facility: Atlantic Research Center LLC
state: New Jersey
city: Skillman
country: United States
facility: Princeton Center for Clinical Research
state: New Jersey
city: Summit
country: United States
facility: Pulmonary & Allergy Associates, P.A.
state: New Jersey
city: Teaneck
country: United States
facility: The Medical Center at Teaneck
state: New Jersey
city: Rochester
country: United States
facility: AAIR Research Center
state: New York
city: White Plains
country: United States
facility: Ira Finegold, M.D.
state: New York
city: Asheville
country: United States
facility: Regional Allergy & Asthma Consultants
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Fargo
country: United States
facility: Allergy & Asthma Care Centre
state: North Dakota
city: Canton
country: United States
facility: Allergy & Respiratory Center
state: Ohio
city: Sylvania
country: United States
facility: Toledo Center for Clinical Research
state: Ohio
city: Altoona
country: United States
facility: Dr. Jeffrey Rosch Office and Research Centre
state: Pennsylvania
city: Easton
country: United States
facility: Valley Clinical Research Centre
state: Pennsylvania
city: Philadelphia
country: United States
facility: Allergy and Asthma Research of New Jersey Inc.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: Upland
country: United States
facility: Asthma and Allergy Associates
state: Pennsylvania
city: Bristol
country: United States
facility: Tricities Medical Research
state: Tennessee
city: Chattanooga
country: United States
facility: The Asthma Institute, PLLC
state: Tennessee
city: Knoxville
country: United States
facility: The Allergy, Asthma & Sinus Centre PA
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates, Inc
state: Tennessee
city: Austin
country: United States
facility: Allergy & Asthma Associates Research Department
state: Texas
city: Austin
country: United States
facility: Lovelace Scientific Resources Allergy and Asthma Centre of Austin
state: Texas
city: Dallas
country: United States
facility: AARA Research Centre
state: Texas
city: Fort Worth
country: United States
facility: North Texas Institute for Clinical Trials
state: Texas
city: Houston
country: United States
facility: Allergy & Asthma Associates
state: Texas
city: San Antonio
country: United States
facility: Biogenics Research Institute
state: Texas
city: San Antonio
country: United States
facility: Diagnostic Research Group
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
city: Waco
country: United States
facility: Allergy & Asthma Care of Waco
state: Texas
city: Waco
country: United States
facility: Allergy Asthma Research Institute
state: Texas
city: South Burlington
country: United States
facility: Timber Lane Allergy & Asthma Research
state: Vermont
city: Richmond
country: United States
facility: Commonwealth Clinic Research Specialists Inc.
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research
state: Virginia
city: Greenfield
country: United States
facility: Allergy, Asthma & Sinus Centre, S.C.
state: Wisconsin
city: Madison
country: United States
facility: Dean Foundation Medical Research
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin, Madison, School of Medicine and Public Health
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Centre For Clinical Trials
state: Wisconsin
city: Milwaukee
country: United States
facility: Advanced Healthcare SC
state: Wisconsin
city: West Allis
country: United States
facility: Allergic Diseases SC
state: Wisconsin
city: Burlington
country: Canada
facility: JBN Medical Diagnostic Services Inc.
state: Ontario
city: Courtice
country: Canada
facility: Co-Medica Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Kanata
country: Canada
facility: Kanata Allergy Services Ltd.
state: Ontario
city: Mississauga
country: Canada
facility: Allied Research International Inc
state: Ontario
city: Mississauga
country: Canada
facility: Alpha Medical Research Inc.
state: Ontario
city: Niagara Falls
country: Canada
facility: Niagara Clinical Research
state: Ontario
city: North Bay
country: Canada
facility: Northgate Medical Clinic
state: Ontario
city: Ottawa
country: Canada
facility: Allergy & Asthma Research Centre
state: Ontario
city: Toronto
country: Canada
facility: Melimar Allergy Laboratory Inc.
state: Ontario
city: Toronto
country: Canada
facility: Asthma, Allergy & Immunology
state: Ontario
city: Toronto
country: Canada
facility: Gordon Sussman, 202 St. Clair Avenue West
state: Ontario
city: Toronto
country: Canada
facility: Manna Research
state: Ontario
city: Mirabel
country: Canada
facility: Omnispec Clinical Research
state: Quebec
city: Montreal
country: Canada
facility: Division of Clinical Immunology and Allergy, The McGill University Health Centre
state: Quebec
city: Sherbrooke
country: Canada
facility: Q&T Research
state: Quebec
city: Quebec
country: Canada
facility: Centre De Recherche Appliquée en Allergie De Quebec
Study officials:
affiliation: Allergy Therapeutics
name: Karl Jürgen Fischer von Weikersthal-Drachenberg, MD
role: STUDY_CHAIR
References: