Efficacy and Safety/Tolerability of Grass MATA MPL

NCT ID: NCT00414141

Last Updated: 2010-06-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1028 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2007-11-30

Brief Summary

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Grass MATA MPL has been developed by Allergy Therapeutics (UK) Ltd. to provide pre-seasonal specific immunotherapy for patients with proven type I hypersensitivity to cross reacting grass 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 Grass MATA MPL versus placebo in grass-allergic subjects following 4 subcutaneous injections of study medication administered before the start of the 2007 grass pollen season.

Detailed Description

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Grass MATA MPL has been developed by Allergy Therapeutics (UK9 Ltd.to provide pre-seasonal specific immunotherapy for patients with proven type I hypersensitivity to cross reacting grass pollens causing rhinitis and/or conjunctivitis with or without mild to moderate asthma bronchiale. Grass MATA MPL is produced as a re-formulation of the Allergy Therapeutics product Pollinex Quattro, which has been used in Europe since 1999 on a 'named patient' basis (with approximately 65,000 treatment courses containing grass pollens).

Grass MATA MPL contains an extract of the 13 grass 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 Grass MATA MPL versus placebo in grass-allergic subjects following 4 subcutaneous injections of study medication administered before the start of the 2007 grass pollen season.

Conditions

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Type I Hypersensitivity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Grass MATA MPL

Group Type EXPERIMENTAL

Grass MATA MPL

Intervention Type BIOLOGICAL

4 subcutaneous injections

2

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

4 subcutaneous injections

Interventions

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Grass MATA MPL

4 subcutaneous injections

Intervention Type BIOLOGICAL

Placebo

4 subcutaneous injections

Intervention Type BIOLOGICAL

Other Intervention Names

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tyrosine solution

Eligibility Criteria

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Inclusion Criteria

* Have given written informed consent;
* Are 18 to 59 years of age;
* Have a history of moderate to severe symptoms of seasonal allergic rhinitis and/or conjunctivitis ascribed to grass pollen exposure that required repeated use of antihistamines, nasal steroids, and/or leukotriene modifiers;
* Have a history of moderate to severe symptoms in the past grass pollen season as determined by a score of ≥ 5 on the Disease Severity Questionnaire;
* Have a positive skin prick test to grass pollen mix \[wheal (longest diameter) ≥ 5 mm greater than the negative control\] and a positive RAST or equivalent test (class ≥ 2) to grass pollen mix;
* Have a positive skin prick test to histamine \[wheal (longest diameter) of ≥ 3 mm greater than the negative control\];
* Have a negative skin prick test to the negative control (redness with wheal ≤ 2 mm is acceptable);
* Have a 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 \[i.e. double barrier method of contraception (e.g., intrauterine device and condom, spermicide and condom), stable hormonal contraceptive for ≥ 90 days prior to the study or if \< 90 days additional use of a double barrier method until 90 days reached, sexual abstinence or have a vasectomized partner until study completion\], and have a negative β-HCG pregnancy test result at Visits 1 and 2;
* Are able to understand and comply with study instructions;
* Demonstrate proper use of electronic diary with at least 85% compliance (i.e., correct entries for symptoms on 6 of 7 days) during the 1-week period between Visit 1 and Visit 2.

Exclusion Criteria

* Are pregnant or lactating
* Have asthma requiring the daily use of controller medication;
* Had an emergency room visit or admission for asthma in the 12 months prior to Visit 1;
* Have the presence of secondary alteration at the affected organ (i.e., emphysema, bronchiectasis, nasal polyps, chronic sinusitis);
* Have auto-immune disease (e.g., liver, kidney, thyroid, nervous system);
* Have 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;
* Have a history or presence of diabetes (both insulin dependent and non-dependent), cancer or concomitant illness (e.g., cardiac, metabolic, renal, hepatic, gastrointestinal, dermatologic, venereal, hematologic, neurologic, or psychiatric diseases or disorders) that, in the opinion of the Investigator, would pose a safety risk or compromise the interpretation of efficacy for this grass immunotherapy;
* Have a history of angioedema;
* Have manifest pulmonary or cardiac insufficiency;
* Have current malignant disease;
* Have disorders of tyrosine metabolism (i.e., alcaptonuria, tyrosinemia);
* Have an acute or chronic infection;
* Have any clinically significant abnormal laboratory value (as determined by the Investigator) at Visit 1;
* Perennial Allergens: Have a positive skin prick test \[wheal (longest diameter) ≥ 3mm greater than the negative control\] at Visit 1 to: house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae), molds (Cladosporium cladosporioides, Alternaria alternata, Penicillium chrysogenum, and Aspergillus fumigatus), or epithelia (cat, dog, and horse). 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. Subjects with mild or no symptoms when exposed to the aforementioned allergens during the 3 years prior to Visit 1 will be allowed to enroll. Mild symptoms are defined as: sign/symptom clearly present, but minimal awareness; easily tolerated;
* Only for the USA and Canada:Autumn/Winter Flowering Plant Allergens: Have a positive skin prick test \[wheal (longest diameter) ≥ 3mm greater than the negative control\] at Visit 1 to: ragweed (Ambrosia sp.) or mountain cedar/mountain juniper (Juniperus ashei). 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 both 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. Subjects with mild or no symptoms when exposed to the aforementioned allergens during the 3 years prior to Visit 1 will be allowed to enroll. Mild symptoms are defined as: sign/symptom clearly present, but minimal awareness, easily tolerated;
* Springtime Flowering Plant Allergens: Applies only to subjects living in geographic areas where springtime flowering plant season and grass season overlap and/or when treatment phase cannot be completed at least 30 days prior to the start of the springtime flowering plant season. Otherwise, no testing of the following allergens is necessary; Have a positive skin prick test \[wheal (longest diameter) ≥ 3mm greater than the negative control\] at Visit 1 to: birch (Betula sp.), oak (Quercus sp.), sycamore/plane (Platanus sp.), beech (Fagus sp.), ash (Fraxinus sp.), or poplar (Populus sp.). 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. Subjects with mild or no symptoms when exposed to the aforementioned allergens during the 3 years prior to Visit 1 will be allowed to enroll. Mild symptoms are defined as: sign/symptom clearly present, but minimal awareness, easily tolerated;
* Only for the USA and Canada:Summertime Flowering Plant Allergens: Have a positive skin prick test \[wheal (longest diameter) ≥ 3mm greater than the negative control\] at Visit 1 to: Bermuda grass (Cynodon dactylon). 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: the listed allergen must not be tested if it is not common to the Investigator's region. Subjects with mild or no symptoms when exposed to the aforementioned allergens during the 3 years prior to Visit 1 will be allowed to enroll. Mild symptoms are defined as: sign/symptom clearly present, but minimal awareness; easily tolerated;
* 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 (e.g., anticholinergic agents and tricyclic antidepressants) 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 (e.g., 2 weeks holiday abroad during the time of diary recording);
* Have changed residence between geographical regions within the past 3 months
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Allergy Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Allergy Therapeutics (UK) Ltd.

Principal Investigators

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Karl Jürgen Fischer von Weikersthal-Drachenberg, MD

Role: STUDY_CHAIR

Allergy Therapeutics

Locations

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Asthma & Allergy Associates, PC & Research Center

Colorado Springs, Colorado, United States

Site Status

Colorado Allergy & Asthma Centers, PC

Denver, Colorado, United States

Site Status

Colorado Allergy and Asthma Clinic, PC

Englewood, Colorado, United States

Site Status

Dr. Dreyfus

Waterbury, Connecticut, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Sneeze, Wheeze & Itch Associates

Normal, Illinois, United States

Site Status

The Allergy and Asthma Center

Fort Wayne, Indiana, United States

Site Status

Medical Associates Clinic

Dubuque, Iowa, United States

Site Status

Iowa Clinical Research Corporation

Iowa City, Iowa, United States

Site Status

Kansas City Allergy and Asthma Associates, PA

Overland Park, Kansas, United States

Site Status

Brigham & Women's Hospital, Rheumatology & Immunology, Smith Building Rm 626

Boston, Massachusetts, United States

Site Status

"The Allergy & Arthritis Family Treatment Centers

Gardner, Massachusetts, United States

Site Status

McGovern Allergy Associates, PC

Springfield, Massachusetts, United States

Site Status

Respiratory Medicine Researdh Institute of Michigan, PLC

Ypsilanti, Michigan, United States

Site Status

Clinical Research Institute

Minneapolis, Minnesota, United States

Site Status

Clinical Research Institute

Plymouth, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

Montana Allergy and Asthma 2900 12th Avenue North Suite 302E

Billings, Montana, United States

Site Status

Montana Medical Research

Missoula, Montana, United States

Site Status

Midwest Allegy and Asthma Clinic

Omaha, Nebraska, United States

Site Status

Creighton University - Allergy & Immunology

Omaha, Nebraska, United States

Site Status

Nebraska Medical Research Institute

Papillion, Nebraska, United States

Site Status

Allergy & Asthma Center

Marlboro, New Jersey, United States

Site Status

Princeton Center for Clinical Research Montgomery Professional Center

Skillman, New Jersey, United States

Site Status

The Medical Center at Teaneck

Teaneck, New Jersey, United States

Site Status

Allergy Consultants, PA

Verona, New Jersey, United States

Site Status

Asthma and Allergy Associates, PC

Cortland, New York, United States

Site Status

Asthma and Allergy Associates, PC

Elmira, New York, United States

Site Status

Aair Research Center

Rochester, New York, United States

Site Status

Island Medical Research, PC

Rockville Centre, New York, United States

Site Status

Allergy & Asthma Care Center

Fargo, North Dakota, United States

Site Status

Merit Care Health

Fargo, North Dakota, United States

Site Status

Allergy and Respiratory Center

Canton, Ohio, United States

Site Status

New Horizons Clinical Research

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Clinical Research Source, Inc.

Perrysburg, Ohio, United States

Site Status

Toledo Center for Clinical Research

Sylvania, Ohio, United States

Site Status

Allergy & Asthma Research Group

Eugene, Oregon, United States

Site Status

Allergy, Asthma and Dermatology Research Center, L.L.C.

Lake Oswego, Oregon, United States

Site Status

Clinical Research Institute of Southern

Medford, Oregon, United States

Site Status

Allergy Associates Research Center, LLC

Portland, Oregon, United States

Site Status

MD Office and Research

Altoona, Pennsylvania, United States

Site Status

Asthma & Allergy Research Assoc Presidents House

Chester, Pennsylvania, United States

Site Status

Penn State University Hershey Medical Center, Dept of Medicine

Hershey, Pennsylvania, United States

Site Status

Allergy and Asthma Research of NJ

Philadelphia, Pennsylvania, United States

Site Status

Allergy & Clinical Immunology Associates

Pittsburgh, Pennsylvania, United States

Site Status

Clinical Partners, LLC

Johnston, Rhode Island, United States

Site Status

Allergy Asthma Immunology Clin RI,Ltd

Providence, Rhode Island, United States

Site Status

Asthma Immunology & Allergy

Chattanooga, Tennessee, United States

Site Status

The Allergy, Asthma, and Sinus Center 801 Weisgarber Road

Knoxville, Tennessee, United States

Site Status

Intermountain Clinical Research

Draper, Utah, United States

Site Status

Allergy Associates of Utah

Murray, Utah, United States

Site Status

Clinical Research Specialists of Utah

Spanish Fork, Utah, United States

Site Status

Timber Lane Allergy & Asthma Research, LLC

South Burlington, Vermont, United States

Site Status

Bellingham Asthma And Allergy Associates

Bellingham, Washington, United States

Site Status

Physicians Pharmaceutical Study Services

Everett, Washington, United States

Site Status

Marycliff Allergy Specialists

Spokane, Washington, United States

Site Status

Spokane Allergy & Asthma Clinical Research

Spokane, Washington, United States

Site Status

Pulmonary Consultants, P.L.L.C.

Tacoma, Washington, United States

Site Status

Allergy Asthma and Sinus Center

Greenfield, Wisconsin, United States

Site Status

Dean Foundation for Health Research & Education, Inc.Med Reseach Dept.

Madison, Wisconsin, United States

Site Status

Advanced Healthcare Clinical Research Center

Milwaukee, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Allergic Diseases, SC

West Allis, Wisconsin, United States

Site Status

Universitätsklinik für Umweltdermatologie

Graz, , Austria

Site Status

Universitätsklinik für Dermatologie und Venerologie

Innsbruck, , Austria

Site Status

Allgemeines Krankenhaus der Stadt Wien - Universitätsklinik für Dermatologie

Vienna, , Austria

Site Status

Allergie-Zentrum Wien West

Vienna, , Austria

Site Status

Kelowna Allergy and Respiratory Health Clinic

Kelowna, British Columbia, Canada

Site Status

Hamilton Medical Research Group

Hamilton, Ontario, Canada

Site Status

McMaster University

Hamilton, Ontario, Canada

Site Status

Kanata Allergy Services Ltd.

Kanata, Ontario, Canada

Site Status

Allied Research International

Mississauga, Ontario, Canada

Site Status

Alpha Medical Research Inc.

Mississauga, Ontario, Canada

Site Status

Niagara Clinical Research

Niagara Falls, Ontario, Canada

Site Status

Northgate Medical Clinic

North Bay, Ontario, Canada

Site Status

Allergy and Asthma Research Centre

Ottawa, Ontario, Canada

Site Status

Filderman R.

Toronto, Ontario, Canada

Site Status

Knight A.

Toronto, Ontario, Canada

Site Status

Sussman G.

Toronto, Ontario, Canada

Site Status

Manna Research

Toronto, Ontario, Canada

Site Status

Omnispec Clinical Research

Mirabel, Quebec, Canada

Site Status

The McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Centre De Recherche Appliquée en Allergie De Québec

Québec, Quebec, Canada

Site Status

Q&T Research

Sherbrooke, Quebec, Canada

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Brighton General Hospital Dept. Respiratory Medicine

Brighton, , United Kingdom

Site Status

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

Ninewells Hospital and Medical School

Dundee, , United Kingdom

Site Status

Glenfield Hospital

Leicester, , United Kingdom

Site Status

Guys Hospital

London, , United Kingdom

Site Status

Lung Function - Northwest Lung Center

Manchester, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Austria Canada United Kingdom

References

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Frew AJ, DuBuske L, Keith PK, Corrigan CJ, Aberer W, Fischer von Weikersthal-Drachenberg KJ. Assessment of specific immunotherapy efficacy using a novel placebo score-based method. Ann Allergy Asthma Immunol. 2012 Nov;109(5):342-347.e1. doi: 10.1016/j.anai.2012.08.013.

Reference Type DERIVED
PMID: 23062390 (View on PubMed)

Other Identifiers

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GrassMATAMPL301

Identifier Type: -

Identifier Source: org_study_id

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