Efficacy and Safety/Tolerability of Grass MATA MPL

Type I Hypersensitivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00414141
• Other study ID #: GrassMATAMPL301
• Status: Completed
• Phase: Phase 3
• First received: December 20, 2006
• Last updated: June 16, 2010
• Start date: November 2006
• Est. completion date: November 2007

Study information

• Verified date: September 2009
• Source: Allergy Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaAustria: Agency for Health and Food SafetyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1028
• Est. completion date: November 2007
• Est. primary completion date: August 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;

• 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 ß-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

Study Design

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

Related Conditions & MeSH terms

• Hypersensitivity
• Hypersensitivity, Immediate
• Type I Hypersensitivity

Intervention

Biological:
• Grass MATA MPL
4 subcutaneous injections
• Placebo
4 subcutaneous injections

Locations

Country	Name	City	State
Austria	Universitätsklinik für Umweltdermatologie	Graz
Austria	Universitätsklinik für Dermatologie und Venerologie	Innsbruck
Austria	Allergie-Zentrum Wien West	Vienna
Austria	Allgemeines Krankenhaus der Stadt Wien - Universitätsklinik für Dermatologie	Vienna
Canada	Hamilton Medical Research Group	Hamilton	Ontario
Canada	McMaster University	Hamilton	Ontario
Canada	Kanata Allergy Services Ltd.	Kanata	Ontario
Canada	Kelowna Allergy and Respiratory Health Clinic	Kelowna	British Columbia
Canada	Omnispec Clinical Research	Mirabel	Quebec
Canada	Allied Research International	Mississauga	Ontario
Canada	Alpha Medical Research Inc.	Mississauga	Ontario
Canada	The McGill University Health Centre	Montreal	Quebec
Canada	Niagara Clinical Research	Niagara Falls	Ontario
Canada	Northgate Medical Clinic	North Bay	Ontario
Canada	Allergy and Asthma Research Centre	Ottawa	Ontario
Canada	Centre De Recherche Appliquée en Allergie De Québec	Quebec
Canada	Q&T Research	Sherbrooke	Quebec
Canada	Filderman R.	Toronto	Ontario
Canada	Knight A.	Toronto	Ontario
Canada	Manna Research	Toronto	Ontario
Canada	Sussman G.	Toronto	Ontario
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Brighton General Hospital Dept. Respiratory Medicine	Brighton
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Ninewells Hospital and Medical School	Dundee
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Guys Hospital	London
United Kingdom	Lung Function - Northwest Lung Center	Manchester
United Kingdom	Southampton General Hospital	Southampton
United States	MD Office and Research	Altoona	Pennsylvania
United States	Bellingham Asthma And Allergy Associates	Bellingham	Washington
United States	Montana Allergy and Asthma 2900 12th Avenue North Suite 302E	Billings	Montana
United States	Brigham & Women's Hospital, Rheumatology & Immunology, Smith Building Rm 626	Boston	Massachusetts
United States	Allergy and Respiratory Center	Canton	Ohio
United States	Asthma Immunology & Allergy	Chattanooga	Tennessee
United States	Asthma & Allergy Research Assoc Presidents House	Chester	Pennsylvania
United States	Rush University Medical Center	Chicago	Illinois
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Asthma & Allergy Associates, PC & Research Center	Colorado Springs	Colorado
United States	Asthma and Allergy Associates, PC	Cortland	New York
United States	Colorado Allergy & Asthma Centers, PC	Denver	Colorado
United States	Intermountain Clinical Research	Draper	Utah
United States	Medical Associates Clinic	Dubuque	Iowa
United States	Asthma and Allergy Associates, PC	Elmira	New York
United States	Colorado Allergy and Asthma Clinic, PC	Englewood	Colorado
United States	Allergy & Asthma Research Group	Eugene	Oregon
United States	Physicians Pharmaceutical Study Services	Everett	Washington
United States	Allergy & Asthma Care Center	Fargo	North Dakota
United States	Merit Care Health	Fargo	North Dakota
United States	The Allergy and Asthma Center	Fort Wayne	Indiana
United States	"The Allergy & Arthritis Family Treatment Centers	Gardner	Massachusetts
United States	Allergy Asthma and Sinus Center	Greenfield	Wisconsin
United States	Penn State University Hershey Medical Center, Dept of Medicine	Hershey	Pennsylvania
United States	Iowa Clinical Research Corporation	Iowa City	Iowa
United States	Clinical Partners, LLC	Johnston	Rhode Island
United States	The Allergy, Asthma, and Sinus Center 801 Weisgarber Road	Knoxville	Tennessee
United States	Allergy, Asthma and Dermatology Research Center, L.L.C.	Lake Oswego	Oregon
United States	Dean Foundation for Health Research & Education, Inc.Med Reseach Dept.	Madison	Wisconsin
United States	Allergy & Asthma Center	Marlboro	New Jersey
United States	Clinical Research Institute of Southern	Medford	Oregon
United States	Advanced Healthcare Clinical Research Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Clinical Research Institute	Minneapolis	Minnesota
United States	Montana Medical Research	Missoula	Montana
United States	Allergy Associates of Utah	Murray	Utah
United States	Sneeze, Wheeze & Itch Associates	Normal	Illinois
United States	Creighton University - Allergy & Immunology	Omaha	Nebraska
United States	Midwest Allegy and Asthma Clinic	Omaha	Nebraska
United States	Kansas City Allergy and Asthma Associates, PA	Overland Park	Kansas
United States	Nebraska Medical Research Institute	Papillion	Nebraska
United States	Clinical Research Source, Inc.	Perrysburg	Ohio
United States	Allergy and Asthma Research of NJ	Philadelphia	Pennsylvania
United States	Allergy & Clinical Immunology Associates	Pittsburgh	Pennsylvania
United States	Clinical Research Institute	Plymouth	Minnesota
United States	Allergy Associates Research Center, LLC	Portland	Oregon
United States	Allergy Asthma Immunology Clin RI,Ltd	Providence	Rhode Island
United States	Aair Research Center	Rochester	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Island Medical Research, PC	Rockville Center	New York
United States	Timber Lane Allergy & Asthma Research, LLC	S Burlington	Vermont
United States	Princeton Center for Clinical Research Montgomery Professional Center	Skillman	New Jersey
United States	Clinical Research Specialists of Utah	Spanish Fork	Utah
United States	Marycliff Allergy Specialists	Spokane	Washington
United States	Spokane Allergy & Asthma Clinical Research	Spokane	Washington
United States	McGovern Allergy Associates, PC	Springfield	Massachusetts
United States	Saint Louis University	St Louis	Missouri
United States	Toledo Center for Clinical Research	Sylvania	Ohio
United States	Pulmonary Consultants, P.L.L.C.	Tacoma	Washington
United States	The Medical Center at Teaneck	Teaneck	New Jersey
United States	Allergy Consultants, PA	Verona	New Jersey
United States	Dr. Dreyfus	Waterbury	Connecticut
United States	Allergic Diseases, SC	West Allis	Wisconsin
United States	Respiratory Medicine Researdh Institute of Michigan, PLC	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Allergy Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Grass MATA MPL versus placebo measured by combined allergy symptom + medication scores during 4 peak weeks of grass 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