E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ICD classification code: J45.0 and J30.1 |
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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 | 10039085 |
E.1.2 | Term | Rhinitis allergic |
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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 | 10001705 |
E.1.2 | Term | Allergic asthma |
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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 aim of this study is to establish superiority of perennial specific immunotherapy with rBet v1-FV over placebo. |
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E.2.2 | Secondary objectives of the trial |
2. to evaluate the safety of the preparation of the folding variant of recombinant major allergen of birch pollen (rBet v1-FV) for perennial treatment 3. to assess immunologic parameters during the course of the study in order to obtain evidence of the immunologic effects of the recombinant major allergen of birch pollen
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male and female outpatients, 18 - 60 years -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 birch pollen and -In the course of the year: major allergy symptoms during birch pollen season and -symptoms of allergic rhinoconjunctivitis against birch pollen allergens requiring medication during the last birch pollen season and -proven clinical relevance of birch pollen allergy by positive conjunctival provocation test result using natural birch pollen extract and -positive skin prick test reaction to natural birch pollen allergens demonstrated by birch pollen allergen wheal diameter >= 3mm (to be demonstrated in a valid skin prick test: negative NaCl control wheal < 3mm, positive Histamine (0.1%) control wheal at least 3mm) and -positive EAST to birch pollen at least 1.5 kU/L to be determined in central laboratory -For female patients: effective contraception 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 oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. No pharmacological interactions are known for hormonal contraceptives and specific immunotherapeutic preparations.
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E.4 | Principal exclusion criteria |
-Previous course of hyposensitation against tree pollens 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 birch pollen season: alder, hazel, beech, Dermatophagoides farinae, Dermatophagoides pteronyssinus, dog, cat:Sensitisation in the Skin Prick Test: wheal diameter of respective interfering allergen ≥ wheal diameter of birch pollen allergen - Sensitisation as determined by Serum EAST -Clinically relevant rhinoconjunctival or respiratory symptoms related to other reasons than allergy -PEF or FEV1 < 80% of predicted normal (ECCS) or uncontrolled bronchial asthma according to the GINA Guidelines (2006) -Febrile infections or inflammation of the respiratory tract at the time of inclusion -Irreversible secondary alterations 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, immuno-complex-induced immunopathies -Severe psychiatric and psychological disorders including impairment of cooperation (e.g. alcohol or drug abuse) -Allergy treatment according to severity of symptoms with other than the following medication during the baseline birch pollen season: ·Levocabastine nasal spray/eye drops (0.5mg/mL each), Loratadine/Cetirizine tablets (10mg), Salbutamol (100µg/puff). ·Treatment of exacerbation of allergic rhinoconjunctivitis and bronchial asthma with a short course of oral corticosteroids is permitted. Treatment with other medication must be stopped 2 weeks prior to start of this study. ·Basic asthma treatment with other medication than short acting bronchodilators -Any prophylactic and any treatment with antiallergic medication in fixed (constant) dosage during the baseline and any birch pollen seasons during the study -Treatment with Beta-Blockers -Pregnancy and lactation 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 - Completed or ongoing treatment with anti-IgE-antibody - Possible dependence of patients on sponsor or investigator - Completed or ongoing long-term treatment with tranquilizer or psychoactive drugs - Contra-indication for adrenalin (for example, acute or chronic symptomatic coronary heart disease, severe hypertension) - Treatment with beta-blocker (locally and systemically) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the change of the symptom medication score from the baseline season to the season after 2 years of double-blind treatment. For this purpose patients will carefully complete diaries over a period of 8 weeks during the baseline and the following two pollen seasons. A symptom medication score (SMS) will be calculated by the daily sum of allergic symptoms and the daily sum of additional antiallergic medication. The accurate keeping of the diary will be checked by the investigator. Due to local and annual variations of birch pollen season it is impossible to define the exact time period for assessment of clinical efficacy (AUC) prior to the start of this study. For statistical analysis the period will therefore be defined at the Blind Review Meeting (BRM) before data base lock and unblinding on the bases of reliable retrospective pollen counts for each study year and study region. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 17 |
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 | 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 | 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 | 5 |
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 | 5 |
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 |