E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
House dust mite induced allergic asthma |
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E.1.1.1 | Medical condition in easily understood language |
Suffer from asthma and being allergic to house dust mites |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001705 |
E.1.2 | Term | Allergic 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 evaluate the efficacy of the ALK house dust mite (HDM) allergy immunotherapy tablet (AIT) (6 Development Unit (DU) and 12 DU) given once daily compared to placebo in subjects with HDM induced asthma, as measured by time to first asthma exacerbation after inhaled corticosteroid (ICS) reduction. |
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E.2.2 | Secondary objectives of the trial |
To determine the effects of ALK HDM AIT on asthma symptoms and immunology.
To evaluate the effects of ALK HDM AIT on lung function, asthma control, safety, symptomatic medication, asthma quality of life, and pharmacoeconomics.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female ≥ 18 years.
• A clinical relevant history consistent with HDM-induced asthma of at least 1 year prior to trial entry.
• Use of an appropriate amount of inhaled corticosteroid (incl. combination products) in accordance with the GINA Guideline step 2-4 for the control of the asthma symptoms for a period of at least 6 months within the past year.
• Dose of ICS after switching should at randomisation be in a range of budesonide 400-1200 mcg.
• Documented reversible airway obstruction.
• Asthma control level above or equal to 1.0 (asthma control questionnaire (ACQ) ≥ 1.0) at screening.
• Asthma control level between 1.0 and 1.5 (1.0 ≤ ACQ ≤ 1.5) at visit 3 (randomisation).
• FEV1 ≥ 70% of predicted value.
• A clinical history consistent with mild to severe HDM-induced allergic rhinitis for at least 1 year.
• Positive SPT response to Der pte and/or Der far. The negative control should be truly negative. A positive SPT response to Der pte and/or Der far is defined as wheal diameter ≥ 3 mm.
• Positive specific IgE against Der pte and/or Der far (≥ IgE Class 2; ≥ 0.70 KU/L). |
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E.4 | Principal exclusion criteria |
• A clinical history of persistent allergic asthma and/or rhinitis caused by an allergen to which the subject is regularly exposed and sensitized (except HDM).
• A clinical history of intermittent allergic asthma and/or rhinitis if the seasonal allergen that may cause symptoms in the ICS reduction period (period 3).
• Previous treatment with immunotherapy with HDM allergen for more than 1 month within the last 5 years.
• Hospitalisation for more than 12 hours due to asthma exacerbation within the last 3 months prior to screening visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time to first asthma exacerbation during period 3 (ICS reduction).
Time to first asthma exacerbation is measured in days from start of period 3 (ICS reduction). The definition of asthma exacerbation used is that the subject must experience one or more of the criteria listed below.
The definition of asthma exacerbation used in this trial is based on the recommendations given in the joint statement from the American Thoracic Society and the European Respiratory Society 2009. The clinical interpretation presented below is based on recommendations from GINA, the joint statement from the American Thoracic Society and the European Respiratory Society 2009 as well as publications covering asthma exacerbations. The cut-off for daytime symptoms is based on recommendations from a multinational board of clinical experts within asthma treatment.
In order to fulfil the criteria for a moderate asthma exacerbation in practice, the subject must experience one or more of the following criteria leading to a change in treatment:
a) Nocturnal awakening(s) due to asthma requiring SABA use for at least 2 consecutive nights or an increase of minimum 0.75 in daily symptom score from baseline value on at least 2 consecutive days.
b) An increase from baseline value in occasions of SABA use on at least 2 consecutive days (a minimum increase of 4 puffs per day).
c) ≥ 20% decrease in PEF from baseline value on at least 2 consecutive mornings or evenings or ≥ 20% decrease in FEV1 from baseline value.
d) Visit to the emergency room or unscheduled visit to the trial centre for asthma treatment not requiring systemic corticosteroids.
The baseline value is the mean value during the last 14 days of the screening period.
If the subject experience one of the following events, this will be characterised as a severe asthma exacerbation:
e) Need of systemic corticosteroids for treatment of asthma symptoms for at least 3 days.
f) Emergency room visit because of asthma, requiring systemic corticosteroids or hospitalisation for more than 12 hours because of asthma.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoints
Key secondary endpoints are:
• Time to first deterioration in asthma symptoms.
Time in days from start of period 3 (ICS reduction) to the first asthma exacerbation fulfilling criterion a), see section 8.6.1 of the protocol.
• Immunology measured at end of trial in terms of specific IgE-blocking factor against HDM allergens.
Other Secondary Endpoints
• Severe asthma exacerbation.
- Time to first severe asthma exacerbation.
Time in days from start of period 3 to the first severe asthma exacerbation fulfilling criterion e) or f), see section 8.6.1 of the protocol.
• Asthma exacerbations during period 3.
- The frequency of asthma exacerbations (number/percentage of subjects) during period 3.
• Asthma symptoms.
- The average overall symptom score over the first asthma exacerbation free period during the first 3 months of period 3.
- The average overall symptom score over the first asthma exacerbation free period during entire period 3.
- Symptom free days during period 3.
A symptom free day is defined as a day with:
o No asthma symptoms (symptom score =0).
o No need for SABA.
o No increase in ICS or use of oral steroid.
• Symptomatic medication.
- Time to first increased use of SABA.
Time in days from start of period 3 to the first asthma exacerbation fulfilling criterion b), see section 8.6.1 of the protocol.
• Lung function.
- The average morning PEF and diurnal variability over the first asthma exacerbation free period during first 3 months of period 3.
- The average morning PEF and diurnal variability over the first asthma exacerbation free period during entire period 3.
- Time to first deterioration in lung function.
Time in days from start of period 3 to the first asthma exacerbation fulfilling criterion c), see section 8.6.1 of the protocol.
- Change in FEV1 from baseline to visit 9 (ICS reduction).
• Asthma control.
- The overall ACQ for the last week of period 2 (treatment maintenance) before period 3 (assessed at visit 9).
• Asthma quality of life.
- The overall AQLQ(s) for the last week of period 2 (treatment maintenance) before period 3 (assessed at visit 9).
• Immunology.
- Specific IgE, IgG4, and other immunological assessments.
• Quality of Life and Pharmacoeconomics Assessments.
- Development and changes in ACQ, AQLQ(s), SF-36, TSQM II, and WPAI:ASTHMA.
- Health care resource use and rate of hospitalisation.
• Safety.
- AEs, SAEs, AE withdrawals, clinical lab tests, vital signs, physical examination. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 3 |
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 | 90 |
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 | No |
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 |
Austria |
Croatia |
Denmark |
France |
Germany |
Lithuania |
Netherlands |
Poland |
Serbia |
Slovakia |
Spain |
United Kingdom |
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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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The end of the trial is defined in the protocol as database closure. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |