E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
IgE-mediated allergic disease manifested as symptoms of allergic rhinitis/rhinoconjunctivitis with or without allergic bronchial asthma (GINA I and II), triggered by grass pollen allergens. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036019 |
E.1.2 | Term | Pollen allergy |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aims of this controlled trial is to obtain evidence for the safety and efficacy of sublingual immunotherapy with grass pollen allergens formulated as solution in comparison to a symptomatic standard treatment with add on placebo in a representative number of grass pollen allergic children suffering from allergic rhinitis/rhinoconjunctivitis with and without asthma bronchiale (GINA I or II). 2. to assess immunologic parameters during the course of the study to obtain evidence of immunologic effects of the therapeutic vaccine. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male and female outpatients •Age 4 – < 12 years •IgE-mediated seasonal allergic rhinitis/rhinoconjunctivitis with or without asthma bronchiale (GINA stage I or II), attributable to grass pollen allergens, documented by positive skin prick test weal for grass pollen at least as large as histaminedihydrochloride (1 %) control reaction or > 5 mm in diameter and positive RAST/CAP > 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 •Rhinitis / Rhinoconjunctivitis symptoms documented in the patient´s diary during the baseline season
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E.4 | Principal 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 (ECCS) •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 β-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)
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |