E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
House Dust Mite (HDM) Allergic Asthma |
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E.1.1.1 | Medical condition in easily understood language |
Asthma that is induced by House Dust Mite allergy |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10038738 |
E.1.2 | Term | Respiratory, thoracic and mediastinal disorders |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
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 |
The primary objective is to demonstrate efficacy of the HDM SLIT-tablet versus placebo as add-on treatment in children and adolescents (5-17 years) with HDM allergic asthma based on clinically relevant asthma exacerbations after at least 4 months of treatment. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objectives are to demonstrate efficacy of the HDM SLIT-tablet versus placebo after at least 4 months as add-on treatment in children and adolescents with HDM allergic asthma with respect to: • Nocturnal awakening due to asthma which require SABA rescue medication • Rescue medication use (SABA) • Lung function (FEV1) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I1. Written informed consent obtained from parents/caregivers before any trial related procedures are performed. Consent or assent from the subject must be obtained according to national requirements. Footnote: At least one parent/caregiver must be able to read. I2. Male or female of any race/ethnicity aged ≥4 to ≤17 years on the day informed consent is obtained from the parent/caregiver. The subject must be ≥5 to ≤17 years old at the randomisation visit I3. A female subject of childbearing potential must have a negative pregnancy test and be willing to practise appropriate contraceptive methods until the follow-up TC I4. A clinical history of HDM allergic asthma of at least 1 year duration diagnosed by a physician I5. Use of low daily dose of ICS plus LABA or medium/high daily dose of ICS with or without LABA for the control of asthma symptoms within the past year prior to randomisation. For definition of ICS doses, please see Table 3 and Table 4 I6. ≥3 clinically relevant asthma exacerbations in the past two years or ≥2 clinically relevant asthma exacerbations in the past year or ≥1 severe asthma exacerbation in the past year prior to randomization while being on asthma controller medication (low dose ICS plus LABA or medium/high dose ICS with or without LABA) . The asthma controller medication at the screening visit must be at a dose equivalent to or below the dose the subject received before the last asthma exacerbation occurred I7. One or more of the following within the past 4 weeks prior to randomisation: a. Daytime asthma symptoms more than twice/week b. Any nocturnal awakening due to asthma which require use of SABA rescue medication c. SABA rescue medication needed for treatment of asthma symptoms more than twice/week d. Any activity limitation due to asthma I8. Lung function measured by FEV1 ≥ 70% of predicted value or according to local requirements while on background treatment following at least a 6-hour washout of SABA at screening and randomisation I9. Clinical history of HDM AR within the last year prior to randomisation I10. An average TCRS>0 during the baseline period (period 2) I11. Positive specific IgE (defined as ≥class 2, ≥0.70 kU/l) against D. pteronyssinus and/or D. farinae at screening I12. Positive SPT to D. pteronyssinus and/or D. farinae at screening I13. Subject willing and able to comply with trial protocol |
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E.4 | Principal exclusion criteria |
E1. Has a clinically relevant history and is sensitized, symptomatic and regularly exposed to animal dander, molds, and/or cockroach (e.g., present in the home, job, school, etc.) or other perennial allergen E2. Has experienced a life-threatening asthma attack defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia requiring non-invasive ventilator support E3. Within the last month before the randomisation visit (visit 3), has had an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalisation, or treatment with systemic corticosteroids E4. Within the last 3 months before the randomisation visit (visit 3) while on high dose ICS treatment, has had an occurrence of any clinical deterioration of asthma that resulted in emergency treatment, hospitalisation, or treatment with systemic corticosteroids E5. SLIT treatment with D. pteronyssinus or D. farinae for more than 1 month within the last 5 years. In addition, any SLIT treatment with D. pteronyssinus or D. farinae within the previous 12 months E6. SCIT treatment with D. pteronyssinus or D. farinae reaching the maintenance dose within the last 5 years. In addition, any SCIT treatment with D. pteronyssinus or D. farinae within the previous 12 months E7. Ongoing treatment with any allergy immunotherapy product E8. Severe chronic oral inflammation E9. Any nasal or naso/oropharyngeal condition that could confound the efficacy or safety assessments (e.g., hypertrophy of the pharyngeal/palatine tonsils, clinically relevant nasal polyps, a history of paranasal sinus surgery or surgery of nasal turbinates) E10. Any clinically relevant chronic disease incl. malignancy that in the opinion of the investigator would interfere with the trial evaluations or the safety of the subject E11. Has a diagnosis or history of eosinophilic oesophagitis E12. A relevant history of systemic allergic reaction e.g. anaphylaxis with cardiorespiratory symptoms, generalised urticaria or severe facial angioedema that in the opinion of the investigator may constitute an increased safety concern E13. Active or poorly controlled autoimmune diseases, immune defects, immunodeficiencies, immunosuppression or malignant neoplastic diseases with current disease relevance E14. Ongoing treatment with OCS E15. Treatment with restricted and prohibited concomitant medication listed in Table 2 E16. Treatment with an investigational drug within 30 days/5 half-lives of the drug (which ever longest) prior to screening E17. A history of allergy, hypersensitivity or intolerance to any of the excipients or active substance of the IMP (except D. pteronyssinus and D. farinae) or to any excipient of the rescue medication provided in this trial E18. A business or personal relationship with trial staff or sponsor who is directly involved with the conduct of the trial E19. A history of alcohol or drug abuse E20. Has previously been randomised into this trial, is participating in this trial at another investigational site or is participating or planning to participate in any other clinical trial during the duration of this trial E21. Has a history or current evidence of any condition, treatment, laboratory values out of range or other circumstance that in the opinion of the investigator are clinically relevant and might expose the subject to risk by participating in the trial, confound the results of the trial, or interfere with the subject’s participation for the full duration of the trial E22. Has a condition or treatment that increase the risk of the subject developing severe adverse reactions after adrenaline/epinephrine administration E23. Is unable to or will not comply with the use of adrenaline/epinephrine auto-injectors for countries where this is a regulatory requirement |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the trial is the annualised rate of clinically relevant asthma exacerbations calculated as the number per year per subject during the efficacy evaluation period (period 4). A clinically relevant asthma exacerbation must be medically confirmed and is defined as asthma worsening leading to at least one of the following criteria: • Doubling of ICS dose compared to background treatment • Systemic corticosteroids for treatment of asthma symptoms for at least 3 days • Emergency room visit due to asthma, requiring systemic corticosteroids • Hospitalisation for more than 12 hours due to asthma, requiring treatment with systemic corticosteroids |
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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) |
The key secondary endpoints are: • Proportion of days with nocturnal awakenings due to asthma requiring SABA rescue medication during the 14 days eDiary recording every 4 months after randomisation • The average daily dose of SABA during the 14 days eDiary recording every 4 months after randomisation • Percentage predicted FEV1 assessed every 4 months after randomisation
Additional secondary efficacy endpoints are: • Time to first clinically relevant asthma exacerbation • Time to recurrent clinically relevant asthma exacerbation • Rate of severe asthma exacerbation during the efficacy period (period 4), defined as asthma worsening leading to at least one of the following criteria: o Systemic corticosteroids for treatment of asthma symptoms for at least 3 days o Emergency room visit due to asthma, requiring systemic corticosteroids o Hospitalisation for more than 12 hours due to asthma, requiring treatment with systemic corticosteroids • Time to first severe asthma exacerbation • Time to recurrent severe asthma exacerbations • ACQ or ACQ-IA Endpoints derived from the two week daily diary collected every 4 months after treatment initiation include: • The average TCRS (TCRS is the sum of the rhinitis daily symptom score (DSS) and the rhinitis daily medication score (DMS)). • Average rhinitis DSS • Average rhinitis DMS • Average rhinoconjunctivitis total combined score (TCS) • Average rhinoconjunctivitis DSS • Average rhinoconjunctivitis DMS • The average combined symptom and medication score (CSMS) • Rhinoconjunctivitis visual analogue scale (VAS) • Average asthma DSS • Asthma VAS • Global evaluation of allergic asthma • Global evaluation of AR |
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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 | No |
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 | No |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
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 |
Russian Federation |
United States |
Bulgaria |
Denmark |
France |
Germany |
Hungary |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |