Efficacy and Safety/Tolerability of Ragweed MATA MPL

Type I Hypersensitivity Clinical Trial

Official title:

Efficacy and Safety/Tolerability of Ragweed MATA MPL, a Randomized, Placebo-Controlled, Double-Blind Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423787
• Other study ID #: RagweedMATAMPL301
• Status: Completed
• Phase: Phase 3
• First received: January 17, 2007
• Last updated: June 16, 2010
• Start date: March 2007
• Est. completion date: March 2008

Study information

• Verified date: June 2010
• Source: Allergy Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 993
• Est. completion date: March 2008
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 59 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypersensitivity
• Hypersensitivity, Immediate
• Type I Hypersensitivity

Intervention

Biological:
• Ragweed MATA MPL
4 injections of increasing dose strength: 300 SU/0.5 ml 700 SU/0.5 ml 2000 SU/0.5 ml 6000 SU/0.5 ml

Locations

Country	Name	City	State
Canada	JBN Medical Diagnostic Services Inc.	Burlington	Ontario
Canada	Co-Medica Health Centre	Courtice	Ontario
Canada	McMaster University	Hamilton	Ontario
Canada	Kanata Allergy Services Ltd.	Kanata	Ontario
Canada	Omnispec Clinical Research	Mirabel	Quebec
Canada	Allied Research International Inc	Mississauga	Ontario
Canada	Alpha Medical Research Inc.	Mississauga	Ontario
Canada	Division of Clinical Immunology and Allergy, The McGill University Health Centre	Montreal	Quebec
Canada	Niagara Clinical Research	Niagara Falls	Ontario
Canada	Northgate Medical Clinic	North Bay	Ontario
Canada	Allergy & Asthma Research Centre	Ottawa	Ontario
Canada	Centre De Recherche Appliquée en Allergie De Quebec	Quebec
Canada	Q&T Research	Sherbrooke	Quebec
Canada	Asthma, Allergy & Immunology	Toronto	Ontario
Canada	Gordon Sussman, 202 St. Clair Avenue West	Toronto	Ontario
Canada	Manna Research	Toronto	Ontario
Canada	Melimar Allergy Laboratory Inc.	Toronto	Ontario
United States	Dr. Jeffrey Rosch Office and Research Centre	Altoona	Pennsylvania
United States	Regional Allergy & Asthma Consultants	Asheville	North Carolina
United States	Allergy & Asthma Consultants	Atlanta	Georgia
United States	Clinical Research Atlanta	Atlanta	Georgia
United States	Allergy & Asthma Associates Research Department	Austin	Texas
United States	Lovelace Scientific Resources Allergy and Asthma Centre of Austin	Austin	Texas
United States	Tricities Medical Research	Bristol	Tennessee
United States	Allergy & Respiratory Center	Canton	Ohio
United States	The Asthma Institute, PLLC	Chattanooga	Tennessee
United States	University Consultants in Allergy/Immunlogy	Chicago	Illinois
United States	DataQuest Medical Research	Conyers	Georgia
United States	AARA Research Centre	Dallas	Texas
United States	Valley Clinical Research Centre	Easton	Pennsylvania
United States	Allergy & Asthma Care Centre	Fargo	North Dakota
United States	North Texas Institute for Clinical Trials	Fort Worth	Texas
United States	Northeast Georgia Research Center LLC	Gainesville	Georgia
United States	Allergy & Arthritis Treatment Centre	Gardner	Massachusetts
United States	Allergy, Asthma & Sinus Centre, S.C.	Greenfield	Wisconsin
United States	Allergy & Asthma Associates	Houston	Texas
United States	Iowa Clinical Research Corporation	Iowa City	Iowa
United States	The Allergy, Asthma & Sinus Centre PA	Knoxville	Tennessee
United States	Allergy and Consultants, PC	Lilburn	Georgia
United States	Dean Foundation Medical Research	Madison	Wisconsin
United States	University of Wisconsin, Madison, School of Medicine and Public Health	Madison	Wisconsin
United States	Centre For Clinical Trials	Menomonee Falls	Wisconsin
United States	Advanced Healthcare SC	Milwaukee	Wisconsin
United States	Clinical Research Institute	Minneapolis	Minnesota
United States	Clinical Research Associates, Inc	Nashville	Tennessee
United States	Sneeze, Wheeze and Itch Associates, LLC	Normal	Illinois
United States	Atlantic Research Center LLC	Ocean	New Jersey
United States	Creighton University Medical Center Division of Allergy, Asthma and Immunology	Omaha	Nebraska
United States	Midwest Allergy and Asthma Clinic	Omaha	Nebraska
United States	Kansas City Allergy & Asthma	Overland	Kansas
United States	The Asthma and Allergy Centre	Papillion	Nebraska
United States	Allergy and Asthma Research of New Jersey Inc.	Philadelphia	Pennsylvania
United States	Allergy and Clinical Immunology Associates	Pittsburgh	Pennsylvania
United States	Clinical Research Institute/West Health Building	Plymouth	Minnesota
United States	North Carolina Clinical Research	Raleigh	North Carolina
United States	Wake Research Associates	Raleigh	North Carolina
United States	Commonwealth Clinic Research Specialists Inc.	Richmond	Virginia
United States	National Clinical Research	Richmond	Virginia
United States	AAIR Research Center	Rochester	New York
United States	Biogenics Research Institute	San Antonio	Texas
United States	Diagnostic Research Group	San Antonio	Texas
United States	Sylvana Research Associates	San Antonio	Texas
United States	Princeton Center for Clinical Research	Skillman	New Jersey
United States	Timber Lane Allergy & Asthma Research	South Burlington	Vermont
United States	The Clinical Research Center, LLC	St. Louis	Missouri
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	Pulmonary & Allergy Associates, P.A.	Summit	New Jersey
United States	Toledo Center for Clinical Research	Sylvania	Ohio
United States	The Medical Center at Teaneck	Teaneck	New Jersey
United States	Asthma and Allergy Associates	Upland	Pennsylvania
United States	Allergy & Asthma Care of Waco	Waco	Texas
United States	Allergy Asthma Research Institute	Waco	Texas
United States	The Centre for Allergy, Asthma & Immunology	Waterbury	Connecticut
United States	Allergic Diseases SC	West Allis	Wisconsin
United States	Ira Finegold, M.D.	White Plains	New York
United States	Respiratory Medical Research Institute of Michigan	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Allergy Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		9 months	No
Secondary	Combined symptom + medication scores, Combined symptoms, Individual symptoms, Relief medication use, Specific immunological changes, quality of life, Health Assessments, Days absent from activities		9 months	No
Secondary	Adverse events, adverse reactions, clinical labs, ECG, and vitals		9 months	Yes