Efficacy and Safety/Tolerability of Ragweed MATA MPL

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

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

Study Overview

• Status: Completed
• Conditions: Type I Hypersensitivity
• Intervention / Treatment: Biological: Ragweed MATA MPL

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.

• Study Type: Interventional
• Enrollment (Actual): 993
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, GIV 4M6
    • Centre De Recherche Appliquée en Allergie De Québec
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • JBN Medical Diagnostic Services Inc.
    • Courtice, Ontario, Canada, L1E 3C3
      • Co-Medica Health Centre
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University
    • Kanata, Ontario, Canada, K2L 3C8
      • Kanata Allergy Services Ltd.
    • Mississauga, Ontario, Canada, L4W 1N2
      • Allied Research International Inc
    • Mississauga, Ontario, Canada, L5A 3V4
      • Alpha Medical Research Inc.
    • Niagara Falls, Ontario, Canada, L2G 1J4
      • Niagara Clinical Research
    • North Bay, Ontario, Canada, P1B2H3
      • Northgate Medical Clinic
    • Ottawa, Ontario, Canada, K1Y 4G2
      • Allergy & Asthma Research Centre
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research
    • Toronto, Ontario, Canada, M3H 3S3
      • Melimar Allergy Laboratory Inc.
    • Toronto, Ontario, Canada, M4P 1P2
      • Asthma, Allergy & Immunology
    • Toronto, Ontario, Canada, M4V 1R2
      • Gordon Sussman, 202 St. Clair Avenue West
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Omnispec Clinical Research
    • Montreal, Quebec, Canada, H3G 1A4
      • Division of Clinical Immunology and Allergy, The McGill University Health Centre
    • Sherbrooke, Quebec, Canada, J1H 4J6
      • Q&T Research
• United States
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • The Centre for Allergy, Asthma & Immunology
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Clinical Research Atlanta
    • Atlanta, Georgia, United States, 30342
      • Allergy & Asthma Consultants
    • Conyers, Georgia, United States, 30013
      • DataQuest Medical Research
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Research Center LLC
    • Lilburn, Georgia, United States, 30047
      • Allergy and Consultants, PC
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergy/Immunlogy
    • Normal, Illinois, United States, 61761
      • Sneeze, Wheeze and Itch Associates, LLC
  • Iowa
    • Iowa City, Iowa, United States, 52244
      • Iowa Clinical Research Corporation
  • Kansas
    • Overland, Kansas, United States, 66210
      • Kansas City Allergy & Asthma
  • Massachusetts
    • Gardner, Massachusetts, United States, 01440
      • Allergy & Arthritis Treatment Centre
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Respiratory Medical Research Institute of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
    • Plymouth, Minnesota, United States, 55441
      • Clinical Research Institute/West Health Building
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • The Clinical Research Center, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Midwest Allergy and Asthma Clinic
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center Division of Allergy, Asthma and Immunology
    • Papillion, Nebraska, United States, 68046
      • The Asthma and Allergy Centre
  • New Jersey
    • Ocean, New Jersey, United States, 07712
      • Atlantic Research Center LLC
    • Skillman, New Jersey, United States, 08558
      • Princeton Center for Clinical Research
    • Summit, New Jersey, United States, 07901
      • Pulmonary & Allergy Associates, P.A.
    • Teaneck, New Jersey, United States, 07666
      • The Medical Center at Teaneck
  • New York
    • Rochester, New York, United States, 14618
      • AAIR Research Center
    • White Plains, New York, United States, 10606
      • Ira Finegold, M.D.
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Regional Allergy & Asthma Consultants
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Allergy & Asthma Care Centre
  • Ohio
    • Canton, Ohio, United States, 44718
      • Allergy & Respiratory Center
    • Sylvania, Ohio, United States, 43560
      • Toledo Center for Clinical Research
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16601
      • Dr. Jeffrey Rosch Office and Research Centre
    • Easton, Pennsylvania, United States, 18045
      • Valley Clinical Research Centre
    • Philadelphia, Pennsylvania, United States, 19115
      • Allergy and Asthma Research of New Jersey Inc.
    • Pittsburgh, Pennsylvania, United States, 15241
      • Allergy and Clinical Immunology Associates
    • Upland, Pennsylvania, United States, 19013
      • Asthma and Allergy Associates
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Tricities Medical Research
    • Chattanooga, Tennessee, United States, 37421
      • The Asthma Institute, PLLC
    • Knoxville, Tennessee, United States, 37909
      • The Allergy, Asthma & Sinus Centre PA
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc
  • Texas
    • Austin, Texas, United States, 78731
      • Allergy & Asthma Associates Research Department
    • Austin, Texas, United States, 78759
      • Lovelace Scientific Resources Allergy and Asthma Centre of Austin
    • Dallas, Texas, United States, 75231
      • AARA Research Centre
    • Fort Worth, Texas, United States, 76132
      • North Texas Institute for Clinical Trials
    • Houston, Texas, United States, 77054
      • Allergy & Asthma Associates
    • San Antonio, Texas, United States, 78229
      • Biogenics Research Institute
    • San Antonio, Texas, United States, 78229
      • Sylvana Research Associates
    • San Antonio, Texas, United States, 78229
      • Diagnostic Research Group
    • Waco, Texas, United States, 76708
      • Allergy & Asthma Care of Waco
    • Waco, Texas, United States, 76712
      • Allergy Asthma Research Institute
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Timber Lane Allergy & Asthma Research
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research
    • Richmond, Virginia, United States, 23226
      • Commonwealth Clinic Research Specialists Inc.
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Allergy, Asthma & Sinus Centre, S.C.
    • Madison, Wisconsin, United States, 53715
      • Dean Foundation Medical Research
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin, Madison, School of Medicine and Public Health
    • Menomonee Falls, Wisconsin, United States, 53051
      • Centre For Clinical Trials
    • Milwaukee, Wisconsin, United States, 53209
      • Advanced Healthcare SC
    • West Allis, Wisconsin, United States, 53227
      • Allergic Diseases SC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; 4 injections of placebo 0.5 ml (2% tyrosine)	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
EXPERIMENTAL: Ragweed MATA MPL; modified Ragweed pollen allergen absorbed to Tyrosine and containing MPL adjuvant	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events, adverse reactions, clinical labs, ECG, and vitals	9 months
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

Collaborators and Investigators

• Sponsor: Allergy Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (ACTUAL): November 1, 2007
• Study Completion (ACTUAL): March 1, 2008

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 17, 2007
• First Posted (ESTIMATE): January 18, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): June 17, 2010
• Last Update Submitted That Met QC Criteria: June 16, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: Allergy; Specific Immunotherapy; Allergoid
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Hypersensitivity, Immediate
• Other Study ID Numbers: RagweedMATAMPL301