| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Allergic rhinitis/rhinoconjunctivitis induced by house dust mites | |
| E.1.1.1 | Medical condition in easily understood language | |
| 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 | 20.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10020419 | | E.1.2 | Term | House dust mite allergy | | E.1.2 | System Organ Class | 100000004870 | |
| 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 the efficacy of the HDM SLIT-tablet compared to placebo in the treatment of HDM allergic rhinitis (AR)
in children (5-11 years of age) based on total combined rhinitis symptoms and medication use (TCRS) during the primary efficacy assessment period. | |
| E.2.2 | Secondary objectives of the trial | The key secondary objectives are to demonstrate the efficacy of the HDM SLIT-tablet compared to placebo during the primary efficacy assessment
period based on:
1. Rhinitis symptoms (based on DSS)
2. Rhinitis medication use (based on DMS)
3. Combined rhinoconjunctivitis symptoms and medication use (based on TCS)
The additional secondary objectives are to evaluate the HDM SLIT-tablet compared to placebo during the primary efficacy assessment period with
respect to:
- Safety and tolerability
- Rhinoconjunctivitis symptoms
- Rhinoconjunctivitis medication use
- Rhinoconjunctivitis quality of life (QoL)
- Asthma symptoms and medication use
-Changes in immunological parameters | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | - Male or female, aged 5-11 years old at randomisation, of any race/ethnicity and weighing 15 kg or more on the day of screening
- A clinical history of AR/C when exposed to HDM (diagnosed by a physician) of 1 year duration or more (with or without asthma) and with
allergic rhinitis symptoms despite having received allergy pharmacotherapy during the previous year prior to the screening visit
- Have a rhinitis DSS of at least 6, or a score of at least 5 with one symptom being severe, on at least 8 of the last 14 days of the baseline period
- Use symptomatic medication for treatment of HDM allergic rhinitis during at least 8 of the last 14 days of the baseline period
- Presence of one or more of the Allergic Rhinitis Impact on Asthma (ARIA) quality of life items due to HDM AR/C during the last 14 days of
the baseline period
- Positive skin prick test (SPT) to D. pteronyssinus or D. farinae at screening
- Positive D. pteronyssinus or D. farinae specific IgE (defined as ≥class 3, ≥3.5 kU/l) at screening
- Lung function measured by FEV1 ≥ 70% of predicted value or according to local requirements at randomisation (visit 3). For subjects having a diagnosis of asthma, FEV1 is measured while on subject's usual asthma medication following at least a 6-hour washout of SABA. The criteria must be fulfilled, unless subject is ≤7 years old and not able to perform reproducible FEV1 manoeuvres despite coaching and is not considered as having a diagnosis of asthma as defined in section 11.5 of this protocol. | |
| E.4 | Principal exclusion criteria | -A clinically relevant history of symptomatic perennial AR/C caused by a perennial allergen source such as animal hair and dander and/or mould,
or symptomatic seasonal AR/C and/or asthma caused by an allergen to which the subject is exposed in the baseline and/or efficacy assessment
period.
- SLIT or SCIT treatment reaching the maintenance dose, with D. pteronyssinus or D. farinae for more than 1 month within the last 5
years. In addition, any SLIT or SCIT treatment with D. pteronyssinus or D. farinae within the previous 12 months
- Treatment with medications with potential impact on efficacy endpoints (e.g. treatment with anti-IgE drugs within 130 days/5 halflives
of the drug (which ever longest) or treatment with antidepressant or antipsychotic medications with antihistaminergic effect)
- Asthma requiring daily use of more than 400 mcg budesonide or equivalent at screening or any clinical deterioration of asthma that resulted in emergency treatment, hospitalisation or treatment with systemic corticosteroids within 3 months prior to randomisation
- Any systemic immunosuppressive treatment, other than glucocorticosteroids, within 130 days prior to screening. Any oral
glucocorticosteroids from 60 days prior to baseline. Any other systemic glucocorticosteroids (depot or parenteral) from 90 days prior to baseline,
- A history of chronic urticaria (> 6 weeks) and/or chronic angioedema (> 6 weeks) within the last 2 years prior to screening that in the opinion
of the investigator may constitute an increased safety concern.
- 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
- Severe chronic oral inflammation
- A diagnosis or history of eosinophilic oesophagitis
- Active or poorly controlled autoimmune diseases, immune defects, immunodeficiencies, immunosuppression or malignant neoplastic
diseases with current disease relevance or any immunosuppressive treatment within 3 months prior to screening
- Known history of allergy, hypersensitivity or intolerance to any of the excipients or active substances of the IMP (except for D. pteronyssinus
and/or D. farinae) or to any excipient of the rescue medication provided in this trial
- May be at greater risk of developing severe adverse reactions after adrenaline/epinephrine administration | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Primary efficacy endpoint during the efficacy assessment period is:
The average daily TCRS
The daily TCRS is the sum of the rhinitis daily symptoms score (DSS) and the rhinitis daily medication score (DMS). | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | During the efficacy assessment period which is the last 8 weeks (period 4) of the approximately 12 months IMP treatment. | |
| E.5.2 | Secondary end point(s) | Key secondary efficacy endpoints during the efficacy assessment period are:
- The average rhinitis DSS
- The average rhinitis DMS
- The average total combined score (TCS)
The daily TCS is the sum of the rhinoconjunctivitis DSS (rhinitis DSS + conjunctivitis DSS) and the rhinoconjunctivitis DMS (rhinitis DMS +
conjunctivitis DMS).
The safety and tolerability endpoints are:
- Treatment-emergent adverse events (TEAEs), solicited AEs, IMP related AEs, treatment-emergent serious adverse events (SAEs), event
of special interest (ESI), TEAEs leading to discontinuation, time to discontinuation due to TEAEs
- Vital signs, physical examination, FEV1 and clinical laboratory values during treatment and at the final visit (visit 7)
Additional secondary efficacy endpoints during the efficacy assessment period are:
- Average rhinoconjunctivitis DSS
- Average rhinoconjunctivitis DMS
- Paediatric rhinoconjunctivitis quality of life questionnaire (PRQLQ)
- Average asthma DSS
- Average daily use of short-acting β2-agonist (SABA)
- Rhinitis mild days
- Rhinitis exacerbation days (days with a rhinitis DSS of 6 or of 5 with
one individual symptom scored 3 (symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping))
- Average rhinitis combined symptom and medication score (CSMS)
The immunologic endpoints are:
- Change from baseline in specific IgE and IgG4 to D. pteronyssinus and D. farina, change in baseline for HDM IgE-Blocking factor (IgE-BF) and
change in baseline for total IgE measured at end of trial (visit 7) | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | | Secondary endpoints will be evaluated during the efficacy asessment period, as specified for applicable endpoints, or througout the trial (safety and tolerability as well as immunologic endpoints). | |
| 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 | 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 | 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 46 |
| 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 | | Canada | | Russian Federation | | Ukraine | | United States | | Bulgaria | | France | | Germany | | Lithuania | | Poland | | Slovakia | | Spain | |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
