ICD classification code: J45.0 and J 30.1 MedDRA version: 14.0 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 10015919 - Eye disorders MedDRA version: 14.0 Level: LLT Classification code 10001705 Term: Allergic asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Cocktail of recombinant major allergens of Phleum pratense
Product Code: rPhleum - Strength 1
Pharmaceutical Form: Suspension for injection
Other descriptive name: recombinant Phleum pr
Sponsors
Allergopharma Joachim Ganzer KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Written Informed Consent - Male and female outpatients, 18-60 years legally competent - Patients suffering from IgE-mediated, moderate to severe seasonal allergic rhinitis with or without controlled bronchial asthma (PEF and/or FEV1 at least 80% predicted normal) attributable to grass pollen - In the course of the year: Major allergy symptoms during grass pollen season - Symptoms of allergic rhinoconjunctivitis against grass pollen allergens requiring medication during the last grass pollen season - Proven clinical relevance of grass pollen allergy by positive conjunctival provocation test (CPT) result using natural grass pollen cocktail. - Positive skin prick test reaction to natural grass pollen allergens demonstsrated by grass pollen allergen weal diameter >= 5mm (to be demonsstrated in a valid skin prick test: Negative NaCl control weal = 3 mm) - Positive EAST to grass pollen >= 1.5 kU/l to be determined in central laboratory - For female patients: effective contracetption and negative pregnancy test result. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectibles, combined or oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. No pharmacological interactins are known for hormonal contraceptives and specific immunotherapeutic preparations. At the Beginning of the Treatment Phase (November 2009): Patients must have demonstrated moderate to severe symptoms of allergic grass pollen disease during the baseline season. Details are described in section 10.1.1 of Trial Protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Previous course of hyposensitisation against grass pollen or unknown other allergens in any pharmaceutical form - Patients who have undergone an unsuccessful course of specific immunotherapy with any allergen - For allergens which interfere with the grass pollen season during May to August (Plantain, Nettle, Cypressus where appropriate, Olive tree, Parietaria officinalis, Alternaria alternata, Cat epithelia, Dermatophagoides farinae, Dermatophagoides pteronyssinus): sensitisation in the Skin Prick Test: ° Weal diameter of respective interfering allergen >= weal diameter of grass pollen allergen ° Sensitisation as determined by serum EAST > 1,5 kU/l - Clinical.y relevant sensitisation has to be excluded in a provocation test - Clinically relevant rhinoconjunctival or respiratory symptoms related to other reasons than allergy - PEF or FEV1 < 80% of predicted normal (ECCS) or uncontrolled/partly controlled bronchial asthma according to the GINA Guidelines (2006) - Febrile infections or inflammation of the respiratory tract at the time of inclusion - Irreversible secondary alternations of the reactive organ (emphysema, bronchiectasis etc.) - Severe acute or chronic diseases, severe inflammatory diseases - Other severe generalised diseases (liver, kidneys, metabolic diseases) - Autoimmune diseases, immune defects including immuno-suppression, immune- complex-induced immunopathies - Severe psychiatric and psychological disorders including impairment of cooperation (i.g. alcohol or drug abuse) - Completed or ongoing long-term treatment with tranquillizer psycho active drug Allergy treatment according to severity of symptoms with other than the following medication during the baseline grass pollen season: ° Levocabastine nasal spray/eye drops (0.5 mg/ml each), ° Loratadine/Cetrizine tablets (10 mg), Salbutamol 100 µg/puff), inhaled steroid in higher doses than 500µg/d Beclomethasonedipropionate/equivalent Treatment of exacerbation of allergic rhinoconjunctivitis and bronchial asthma with a short course oforal corticosteroids permitted. Treatment with or other medication must be stopped 2 weeks prior to start of this study ° Basic asthma treatment with other medication than short acting bronchodilatators and inhaled corticosteroids higher than 500µg Beclomethasonedipropionate or equivalent Any prophylactic and any treatment with antiallergic medication in fixed (constant) dosage during the baselilne and any grass pollen seasons during the study - Pregnancy and location period - Female patients seeking to become pregnant - Concurrent participation in any other clinical trial or participation in any other clinical trial during the previous 30 days - Low compliance or inability to understand instructions / study documents -Patients committed to a mental hospital by government or court - completed or ongoing treatment with Anti-EgE antibody - Patients being in any relationship of dependence with the sponsor and/or investigator - Contraindication for adrenaline, (e.g. acute or chronic symptomatic coronary heart disease, severe arterial hypertension) - Treatment with beta-Blockers, locally and systemically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this study is to establish superiority of perennial specific immunotherapy with an aluminium-hydroxide-adsorbed cocktail of re-combinant major allergens of Timothy Grass (Phleum pratense) over placebo. Changes of the Rhinoconjunctivitis Symptom Medication Score (RC-SMS) from the baseline season to the season after 2 years of double-blind treat-ment will be evaluated. The RC-SMS will be calculated by the daily sum of symptoms and the use of anti-allergic medication documented in patient diaries dur-ing grass pollen season. Documentation period of patient diaries covers 12 weeks. The exact period of analysis of clinical efficacy (AUC) will be defined at the Blind Review Meeting (BRM) before data base lock and unblinding on the basis of the real pollen counts occurred in each study year and region. ;Secondary Objective: Changes of rhinoconjunctivitis specific Quality of Life at peak pollen season. Changes of specific conjunctival reactivity to grass pollen allergens. Changes of RC-SMS after the first treatment year. Changes of overall symptom medication score of rhinoconjunctivitis and asthma (SMS) Response (Improvement of AUC of RC-SMS of at least 40% after 2 years of treatment) Immunologic changes specific IgE, IgG1, IgG4. Safety of treatments during the entire study period. ;Primary end point(s): The aim of this study is to establish superiority of perennial specific immunotherapy with an aluminium-hydroxide-adsorbed cocktail of re-combinant major allergens of Timothy Grass (Phleum pratense) over placebo. Changes of the Rhinoconjunctivitis Symptom Medication Score (RC-SMS) from the baseline season to the season after 2 years of double-blind treat-ment will be evaluated. The RC-SMS will be calculated by the daily sum of symptoms and the use of anti-allergic medication documented in patient diaries dur-ing grass pollen season. Documentation period of patient diaries covers 12 weeks. The exact period of analysis of clinical efficacy ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes of rhinoconjunctivitis specific Quality of Life at peak pollen season. Changes of specific conjunctival reactivity to grass pollen allergens. Changes of RC-SMS after the first treatment year. Changes of overall symptom medication score of rhinoconjunctivitis and asthma (SMS) Response (Improvement of AUC of RC-SMS of at least 40% after 2 years of treatment) Immunologic changes specific IgE, IgG1, IgG4. Safety of treatments during the entire study period. ;Timepoint(s) of evaluation of this end point: Safety: interim analysis Study evaluation after 2 years treatment. | — |
Countries
Germany
Outcome results
None listed