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 inflamatory disease of the airways characterized 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 | 18.0 |
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 |
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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 asthma during grass pollen season (GPS)
To investigate the proportion of subjects with and without asthma when comparing Grazax and placebo after the end of trial
To investigate the efficacy of Grazax compared to placebo based on visual analogue scale (VAS) scoring of rhinoconjunctivitis symptoms in the GPS
To investigate the effect 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 |
Females and males 5-12 years of age at time of randomisation
Written informed consent obtained from parents/guardians
Assent from subject, according to national guidelines
A clinical relevant history of grass pollen induced allergic rhino-conjuctivitis having received symptomatic treatment during the GPS 2009 and 2010,
Positive Skin Prick Test (SPT) reponse (wheal diameter ≥ 3 mm) to Phleum pratense
Positive specific IgE against Phleum Pratense (≥ IgE Class 2)
Female subjects, who are fertile must have a negative pregnancy test |
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E.4 | Principal exclusion criteria |
A clinical relevant history of symptomatic seasonal allergic rhinitis and/or conjunctivitis caused by an allergen other than grass overlapping the GPS.
A clinical relevant history of symptomatic perennial allergic rhinitis and/or conjuctivitis caused by an allergen, to which the subject is regularly exposed.
Not capable of perfoming reproducible lung function tests
A medical history of astma and/or wheezing within the last two years.
A medical hsiotry of asthma and/or wheezing since the 5th birthday.
Use of asthma medication within the last 12 month, to treat respiratory and/or pulmonary symptoms which resulted in a clinical relevant effect.
An increase in FEV-1 of ≥ 12% after administration of a beta-2-agonist
Investigator diagnosed asthma
Diurnal PEF variability > 20% for at least 3 out of 14 consecutive days
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
the evaluation of the primary end point will be performed after the end of trial |
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E.5.2 | Secondary end point(s) |
• Time to onset of asthma in GPS
• Asthma status (yes/no) (i.e. status of being asthma symptom free since last visit, defined as when a subject is neither under treatment for asthma nor hass experienced asthma symptoms (any episodes of wheeze, cough, shortness of breath or chest tightness) since last visit) at end of trial
• VAS score of rhinoconjunctivitis symptoms.
o Measured yearly at the in-season GPS visit
o 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 visit 1, visit 10 and visit 15
Endpoints recorded at yearly GPS visits:
• Severity of grass pollen induced allergic rhinitis, according to ARIA categories
• During the past 7 days:
o Average number of days that hay fever symptoms "interfere with getting you to sleep at night", "wake you up at night", "waking up other
family members at night"
o How often did your hay fever symptoms stop you from participating in recreational or physical activities (sports, outdoor activities, going for
a walk, hobbies, etc.)?
o How often did your hay fever symptoms stop you from participating in social activities (activities with family or friends, playing with friends, etc.)?
o Rate of hay fever control
o How often did you use your hay fever medications (antihistamine tablet, eye-drops or nasal spray)?
• During a 5 day school/work week:
o Average number of days that your hay fever symptoms stop you from attending school/work
o How often did your hay fever symptoms interfere with your concentration/ability to work properly at school/work?
• Compared to your hay fever symptoms in the previous grass pollen season, how have you felt overall in this grass pollen season?
Daily recording during the 14 days prior to 2015 GPS 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 end points will be performed after the end of 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
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 | 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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End of trial is when the last subject has completed Visit 15 ( last visit) |
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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 | 0 |