| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Patients have to suffer from IgE mediated allergic rhinits, rhinoconjunctivitis +/- asthma due to sensitization again birch pollen. | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10036019 | |
| 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 | | For the primary criterion, the area under the curve for the symptom load over the time of exposition will be compared. During the pollen flight time, the active treated group should have a lower symptom load in comparison to the placebo group. | |
| E.2.2 | Secondary objectives of the trial | Secondary parameter considered in this trial will be the following:
- symptom score
- medication score
- specific antibody concentrations (IgG1, IgG4, IgE)
- pollencount for the different time intervals
- adverse events
- oral allergy syndrome
- quality of life | |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | - Patients of both gender at an age from 6 up to 45 years
- Prior to study specific examinations, the patient has to give his/her written informed consent. If patients under legal age will be included, the informed consent must be signed by at least one of the parents or the legal responsible guardian.
- The patients have to suffer from seasonal complaints (rhinitis and/or rhinoconjunctivitis with or without allergic asthma) caused by clinical sensitisation
against birch pollen. The sensitisation against birch pollen has to be verified by
- suggestive medical history
- a positive skin prick test for birch pollen, resulting in a wheal diameter of at
least 4 mm > negative control reaction or '++' versus histamine
- specific IgE for birch pollen >= 2
- Patient’s perception of disease activity of at least 30 mm on a 100 mm visual analogue scale (VAS) | |
| E.4 | Principal exclusion criteria | - pregnant or lactating women
- women of child-bearing age not employing sufficient contraceptive protection
- clinical relevant manifestation - defined as positive suggestive history within the last 12 months checked by a comprehensive questionnaire of symptoms, confirmed by a positive skin prick test (wheal diameter of at least 4 mm > negative control reac-tion or '++' versus histamine) as well as by specific IgE (Rast I or higher) - of the following allergies:
- a perennial allergy against house dust mites (Dermatophagoides pteronyssinus or D. farinae), animal epithelia (of cats or dogs) or mould
- a seasonal allergy against grasses (included rye) or weeds
- participation in an immunotherapy with comparable extracts within the last five years
- participation in another clinical trial within the last 3 month prior to this study
- any contra-indication for the unspecific bronchial challenge test
- smokers with a manifested bronchopathy
- alcohol- or drug abusers
- persons, who are obviously not compliant
- patients with other known concomitant diseases:
- acute tuberculosis
- inflammatory or infectious diseases of the target organs effective
- advanced secondary changes at the target organ (e.g. emphysema or bronchiectasis)
- immunopathological diseases (e.g. of the liver, kidney, the nervous system, thyroid gland, rheumatic diseases) in which autoimmune mechanisms play a role
- immune deficiencies
- history of status asthmaticus, heart- and vascular insufficiency, treatment with beta-blockers
- any disease which prohibits the use of adrenaline (e. g. hyperthyroidism)
- serious psychiatric / psychological disturbances
- concomitant treatment with substances interfering with the immune system
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | The main parameter in this study is the symptom load during the predefined pollen season. It is defined as the time weighted area under the curve of the daily symptom load including all days of the pollen season. The daily symptom load is the sum of the daily rescue medication score and the daily symptom severity score.
At the initial and all subsequent examinations, patients will be questioned about their allergic symptoms and the intensity. The same questions are listed in the patient diary. Before the pollen season, the patients will document their symptoms every two weeks, during the pollen season daily.
Symptom severity:
Every day / every second week the severity of the day’s/week’s sneezing, itchy nose, runny nose, stuffy nose, itchy eyes, watery eyes and red eyes are evaluated (on a per-symptom basis) using a following 4-point scale.
Symptom duration
Every day/week the duration of the day’s itchy nose, runny nose, stuffy nose, itchy eyes, watery eyes, and red eyes are evaluated (on a per symptom basis) using a 4-point scale.
The weekly/daily symptom severity score of a patient is the mean of all single scores, i.e. the weekly/daily score is ranging from 0 to 3.
Any rescue medication which is known to have an influence on the typical allergic symptoms is taken into account for the calculation of the weekly/daily rescue medication score. The medication is recorded in the patient’s diary. The following rescue medication will be dispensed and taken into account. Based on the patients condition the following order should be followed:
- 1. topical nasal medication excluding nasal corticosteroids (disodiumcromoglycate)
- topical ocular medication excluding topical ocular corticosteroids (disodiumcromoglycate)
- systemic antihistamines (cetirizine)
- 2. topical pulmonary medication excluding inhaled corticosteroids (salbutamol)
- topical nasal and/or pulmonary corticosteroids (mometasonfuroate, budesonide)
- 3. systemic corticosteroids (methylprednisolone 2mg/kg b.w.) for three days
- The rescue medication score of a patient is the area under the curve of all daily rescue medication scores of this patient including all days of the pollen season.
The investigator will be responsible for an accurate instruction of the patient including an appropriate documentation of the drug account. Rescue medication will be provided to the patient before the start of the pollen season. | |
| 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 | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | | The trial ends after the last visit of the last patient undergoing the trial. The principal investigator may terminate the study at any time, for safety reasons. The sponsor may end the study for security, ethical or administrative reasons. In such instances, all investigators shall be notified in writing, outlining reasons for the termination. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 9 |
