E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The aim of the trial is to investigate whether three consecutive years of treatment with Grazax (75.000 SQ-T) reduces the risk of developing asthma in children compared to placebo. |
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E.1.1.1 | Medical condition in easily understood language |
Asthma is the common chronic inflammatory disease of the airways characterised by variable and recurring symptoms,reversible airflow obstruction and bronchospasm. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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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 |
To investigate the effect of Grazax compared to placebo on the risk of developing asthma in children with hay fever
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of Grazax compared to placebo on the risk of developing seasonal asthma(during grass pollen season only) To investigate the proportion of subjects with and without asthma when comparing Grazax and placebo after the end of the trial.
To investigate the efficacy of Grazax compared to placebo based on visual analogue scale (VAS) scoring of hay fever symptoms during in the grass pollen season.
To investigate the effects of GRAZAX compared to placebo on immunological parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Females and males 5-12 years of age at time of randomisation 2.Written informed consent obtained from parents/guardians 3.Assent from subject, according to national guidelines 4.A clinical relevant history of grass pollen induced allergic rhino-conjuctivitis having received symptomatic treatment during the grass pollen seasons 2009 and 2010, 5.Positive Skin Prick Test (SPT) response (wheal diameter ≥ 3 mm) to Phleum pratense 6.Positive specific IgE against Phleum Pratense (≥ IgE Class 2) 7.Female subjects, who are fertile must have a negative pregnancy test |
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E.4 | Principal exclusion criteria |
1.A clinical relevant history of symptomatic seasonal allergic rhinitis and/or conjunctivitis caused by an allergen other than grass overlapping the grass pollen season. 2.A clinical relevant history of symptomatic perennial allergic rhinitis and/or conjuctivitis caused by an allergen, to which the subject is regularly exposed. 3.Not capable of perfoming reproducible lung function tests 4.A medical history of asthma and/or wheezing within the last two years. 5.A medical history of asthma and/or wheezing since the 5th birthday. 6.Use of asthma medication within the last 12 month, to treat respiratory and/or pulmonary symptoms which resulted in a clinical relevant effect. 7.An increase in FEV1 of ≥ 12% after administration of a beta-2-agonist 8.Investigator diagnosed asthma 9.Diurnal PEF variability > 20% for at least 3 out of 14 consecutive days 10.A clinical history of chronic rhinosinusitis during the last 2 years 11. Previous treatment by immunotherapy with grass pollen allergen or a cross-reacting allergen 12. Inflammatory conditions in the oral cavity with severe symptoms such as oral lichen planus with ulcerations or severe oral mycosis at randomisation 13. Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infectious process at randomisation 14. History of anaphylaxis with cardiorespiratory symptoms (food allergy, drugs etc.) 15. History of recurrent urticaria during the last 2 years 16. A history of facial angioedema or a family history of heritable angioedema 17. Currently treated with tricyclic antidepressants or mono amine oxidase inhibitors (MAOIs) 18. Subject with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or optimal participation in the trial 19. History of allergy, hypersensitivity or intolerance to the excipients of IMP (except for Phleum pratense) 20. Use of an investigational drug within 30 days prior to screening 21. Being immediate family of the investigator or trial staff, defined as the investigator's/staff’s child or grandchild
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E.5 End points |
E.5.1 | Primary end point(s) |
Time of onset of asthma. The evaluation of the primary endpoint will be performed after the end of the trial. |
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E.5.2 | Secondary end point(s) |
Time to onset of asthma in GPS
Asthma status (yes/no)(ie status of being asthma symptom free since last visit,defined as when a subject is neither under treatment for asthma nor has experienced asthma symptoms( any episodes of wheeze cough, shorrtness of breath or chest tightness) since last visit) at the end of trial.
VAS score of rhinoconjunctivitis symptoms - Measured yearly at the in season GPS visit -Average daily VAS score, averaged over the 14 days prior to 2015 GPS visit ( visit 14)
Level of specific IgE,IgG4,and IgE blocking factor against Phleum pratense at visits 1,10 and 15.
End points recorded at yearly GPS visits: -Severity of Grass Pollen Induced Rhinitis,acciording to ARIA catagories
During the past 7 days: - Average number of days that hayfever symptoms "interfere wirth getting you to sleep at night", "wake you up at night","waking up up other family members at night" - How often did your hayfever symptoms stop you from participating in recreational or physical activities ( sports,outdoor activities,hobbies etc.)? - How often did your hayfever symptoms stop you from paticipating in social activities. - Rate of hayfever control - How often did you use your hayfever medications ( antihistamines,eydrops or nasal spray)
During the 5 day school/work week : -Average number of days that your hayfever symptoms stop you from attending school/work - How often did your hayfever symptoms interfere with your concentration/ability to perform properly
Compared to your Hayfever symptoms in the previous grass pollen season how have you felt overall in this grass pollen season. - Daily recordings in the last 14 days prior to 2015 grass pollen season visit ( visit 14) - Average use of Allergic Rhinoconjunctivitis medication
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The evaluation of the secondary endpoints will be performed after the end of the trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 | No |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 29 |