IgE-mediated allergic disease manifested as symptoms of allergic rhinitis/rhinoconjunctivitis with or without allergic bronchial asthma (GINA I und II) triggered by grass pollen allergens. MedDRA version: 18.1 Level: PT Classification code 10048908 Term: Seasonal allergy System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: 6-Grass-Preparation
Product Code: AL0506st
Pharmaceutical Form: Oral drops, solution
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 40-
Sponsors
Allergopharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male and female outpatients •Age 4 – 5 mm in diameter and ?positive EAST > class 2 to grass pollens and ?proven clinical relevance of grass pollen allergy by positive conjunctival provocation testing with grass pollen allergens •For female patients with childbearing potential: Negative pregnancy test and effective contraception •For patients with Asthma bronchiale at entry: specialist confirmed diagnosis and asthma classification as GINA grade I or II •Written informed consent At the beginning of the treatment phase: •Patients must have demonstrated a symptom score of at least 4 every day during the week following the peak pollen count in the baseline season (patients with less symptoms in the baseline season 2008 can repeat the baseline season in 2009) •Rhinitis / Rhinoconjunctivitis symptoms documented in the patients’ diary during the baseline season For the treatment free follow-up investigation: • Male and female outpatients, previously participating in and completed treatment phase of the clinical trial AL0506st • For female patients with childbearing potential: Negative pregnancy test and effective contraception • Written informed re-consent for follow-up investigation Are the trial subjects under 18? yes Number of subjects for this age range: 230 F.1.2 Adults (18-64 years) no 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 or other current specific immunotherapy with grass pollen allergens in any formulation •Symptoms related to or strong skin test positivity to other seasonal or perennial allergens (skin prick test weal > 5 mm and/or as large as histaminedihydrochloride (1%) control reaction, if clinical relevance cannot be excluded), which are effective in the same period as the relevant grass pollens (June – August) •Previous course of hyposensitisation against grass pollen or other allergens that are not known •Specific immunotherapy with any other allergens during the course of the study •Patients that have undergone an unsuccessful course of specific immunotherapy with any allergen •Clinically relevant rhinoconjunctival or respiratory symptoms related to other reasons •Peak Flow < 80% of predicted normal •Severe bronchial asthma (GINA grade III and IV) •Allergy treatment according to severity of symptoms with other than the following medication during the grass pollen season: Levocabastine nasal spray/eye drops, Loratadine tablets, Cetirizine juice / tablets, Salbutamol and short course treatments on prescription with nasal corticosteroids or oral corticosteroids. •Febrile infections or inflammation of the respiratory tract at the time of inclusion •Severe acute or chronic diseases, severe inflammatory diseases (liver, kidneys, metabolic diseases) •Autoimmune diseases, immune-defects including immuno-suppression, immune-complex-induced immunopathies •Previous or ongoing use of anti-IGE antibodies, tranquilizers or psychoactive medicine •Severe psychiatric and psychological disorders including impairment of cooperation (e.g. alcohol or drug abuse) •Treatment with ß-blockers •Recurrent seizures •Pregnancy and lactation period •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 being in any relationship of dependence with the sponsor and/or with the investigator •Patients, who are institutionalised due to a official or judicial order •Mentally disabled minors •Contra-indications for application of adrenaline (e.g. severe acute or chronic symptomatic coronary heart disease, severe arterial hypertension) For the treatment free follow-up investigation: • Specific immunotherapy with grass pollens or any other allergens after the last dose of study drug. • Allergy treatment according to severity of symptoms with other than the following medication during the grass pollen season: Levocabastine nasal spray/eye drops, Loratadine tablets, Cetirizine juice/tablets, Salbutamol and short course treatments on prescription with nasal corticosteroids or oral corticosteroids. • Previous or ongoing use of anti-IgE antibodies, tranquilizers or psychoactive medicine • Severe psychiatric and psychological disorders including impairment of cooperation (e.g. alcohol or drug abuse) • Recurrent seizures • Pregnancy and lactation period • 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 being in any relationship of dependence with the sponsor and/or with the investigator • Patients, who are institutionalised due to a official or judicial order • Mentally disabled minors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): This is a confirmatory phase III pivotal study. The primary endpoint is the change of the area under the curve (AUC) of the SMS (cf. chapter 7). The primary analysis will be the comparison of the change of the AUC at baseline to the measurement after 1 year treatment. That means that the primary analysis will be done with combined data from 2009 (patients of screening phase 1) and 2010 (patients of screening phase 2). The data after the second treatment year from patients of screening phase 1 will not be considered in the primary analysis. Based on the actual pollen count in the respective year, the AUC of the daily SMS-scores will be calculated over a certain time period to be defined at the Blind Review Meeting. The statistical null-hypothesis of no difference between the change of AUC of both treatment groups will be tested in a confirmatory sense within the Full Analysis Set with an analysis of variance (ANOVA) model adjusting for gender, year of baseline and center, the treatment effect will be tested at a two-sided significance level of 0.05. The ANOVA model will be used to estimate the mean adjusted treatment effect and the corresponding 95% confidence interval. All further statistical tests will be performed in an exploratory sense only. In addition, the treatment effect by gender, year of baseline and center will be described univariately and estimated with corresponding ANOVA models with the corresponding covariate in addition to treatment. A univariate, descriptive analysis of the change of AUC after 1 year will be performed- overall as well as by gender, year of baseline and center.;Timepoint(s) of evaluation of this end point: Primary analysis will be done with combined data from 2009 (patients of screening phase 1) and 2010 (patients of screening phase 2);Main Objective: The primary endpoint of this study is to establish superiority of sublingual perennial specific immunotherapy with the liquid preparation of grass pollen over | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in IgE, IgG1 and IgG4 from start of the therapy to end of pollen season Occurrence of Adverse Events after treatment start Changes in specific conjunctival provocation test Symptom and medication score (SMS) after 1, 2 and 3 years of treatment Changes of the area under the curve of the SMS after 2 years and after the full course of 3 years of treatment will be analysed descriptively by treatment and in an exploratory sense also by strata of AUC of SMS at baseline Response For the treatment free follow-up: • AUC of SMS during the 1st and 2nd (= 4th and 5th grass pollen season) year after the end of the full 3 years treatment course compared to previous years. • Well Days: Number of days with Symptom Score = 4 and Medication Score = 0 within the analysis period (42 days) of the 1st and 2nd (= 4th and 5th grass pollen season) year after the end of the full 3 years treatment course. • Cured Allergy: Percentage of patients with at most one mild symptom in mean during the analysis period (42 days) of the 1st and 2nd (= 4th and 5th grass pollen season) year after the end of the full 3 years treatment course. ;Timepoint(s) of evaluation of this end point: Depending on the availablity of data, after end of double blind phase 2010 and/or after the end of the study in autumn 2013 The data of the treatment free follow-up investigation will be analysed depending from the further treatment group after the 4th and 5th grass pollen season in autumn 2014 and 2015 | — |
Countries
Germany
Contacts
Public ContactDepartment of Clinical Trials
Allergopharma GmbH & Co. KG
Outcome results
None listed