Prevention of childhood asthma using house dust mite allergen tablets

Approved 08/09/2025, Nottingham 2 Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8065; nottingham2.rec@hra.nhs.uk), ref: 25/EM/0185

At final year 3 visit:
A. *Recurrent wheeze (2 or more wheezing episodes) in the last 12 months of treatment AND
B. **Positive SPT and/or sIgE to one or more common allergens during the last 12 months
* A wheezing episode is defined as parental or documented report of an episode of wheezing or whistling in the chest that lasts at least 24 hours. Wheezing events separated by at least 5 consecutive days without wheezing shall be counted as separate episodes.
**The common allergens include HDM in duplicate (Dermatophagoides pteronyssinus and Dermatophagoides farinae), grass mix, tree mix, cat, dog, cow’s milk, egg, peanut), as assessed both by; 1) SPT ≥3 mm wheal diameter, OR 2) sIgE ≥0.35 kU/litre.

3 years post randomisation, in the last 12 months, 1-2 years post randomisation, over 3 years of the study:

1. Allergic Sensitisation and Allergic Disease
1.1 Proportion of participants with ARW assessed at 3 years post-randomisation. Atopy defined as per the primary endpoint and wheeze defined as per the primary endpoint but excluding wheeze episodes occurring only in March to August (inclusive).
1.2 Proportion of participants at 3 years post-randomisation with allergic sensitisation to HDM, as assessed by 1) SPT ≥ 3mm and/or 2) sIgE ≥0.35 kU/litre and recurrent wheeze during the last 12 months.

2. Allergic Sensitisation
2.1 Cumulative proportion of participants with sensitisation to one or more common allergens over the 3 years of study. The common allergens include HDM (D. pteronyssinus and D. farina), cockroach, grass pollen, tree pollen, ragweed pollen, cat, dog, cow’s milk, egg, peanut), as assessed both by 1) SPT ≥3 mm and/or 2) sIgE ≥0.35 kU/litre.
2.2 Cumulative proportion of participants with allergic sensitisation to HDM over the 3 years of study, as assessed by 1) SPT ≥ 3mm and/or 2) sIgE ≥0.35 kU/litre.

3. Allergic Disease
3.1 Proportion of participants with ARW at 1- and 2-years post-randomisation:
(a) Recurrent wheeze: defined as two or more separate wheezing episodes in the last 12 months treatment period. A wheezing episode is defined as parental or documented report of an episode of wheezing or whistling in the chest that lasts at least 24 hours. Wheezing events separated by at least 5 consecutive days without wheezing shall be counted as separate episodes.
(b) Atopy: Sensitisation to one or more common allergens in the last 12 months treatment period. The common allergens include HDM (D. pteronyssinus and D. farina), cockroach, grass pollen, tree pollen, ragweed pollen, cat, dog, cow’s milk, egg, peanut), as assessed by SPT ≥3 mm.
3.2 Proportion of participants with allergic rhinitis in the 12 months before the final study visit at 3 years post-randomisation, as assessed by the Allergy and Environment questionnaire based on the standardised ISAAC questionnaire, and evidence of allergic sensitisation to the relevant allergen.
3.3 Proportion of participants with atopic dermatitis (AD) recorded using standard criteria in the 12 months before the final study visit at 3 years post-randomisation, using standardised criteria.
3.4 Proportion of participants with any recurrent wheeze assessed at 3 years post-randomisation (recurrent wheeze defined in 3.1(a)).
3.5 Impulse Oscillometry: Summaries of air flow measurements at the final visit at 3 years post-randomisation.
3.6 Proportion of participants with abnormal exhaled nitric oxide (FeNO) at the final visit at 3 years post-randomisation where a cutoff of < 20 parts per billion (ppb) will be considered normal, as per ATS guidelines.
3.7 Summaries of peak flow measurements at the final visit at 3 years post-randomisation.

4. Safety
4.1 Proportion of participants with any adverse events
4.2 Proportion and incidence with clinically relevant asthma exacerbations over 3 years
4.3 Proportion and incidence with clinically relevant anaphylactic reactions, anaphylaxis and/or systemic allergic reactions over 3 years
4.4 Proportion and incidence treated with adrenaline/epinephrine over 3 years
4.5 Proportion and incidence with severe local swelling or oedema of the mouth and/or throat over 3 years
4.6 Proportion and incidence with eosinophilic esophagitis over 3 years
4.7 Proportion with an increase in proportion and incidence of HDM sensitisation over 3 years

5. Tolerability
5.1 Proportion of participants who stop treatment prior to planned 3 years of treatment of active HDM tablet compared with placebo
5.2 Proportion of participants who stop treatment due to adverse events prior to planned 3 years of treatment of active HDM tablet compared with placebo
5.3 Proportion of participant who took 60% of the treatment over 3 years as recorded in the MedSearchTM App

6. Mechanistic
6.1 Functional IgG and IgA antibodies linked to the prevention of asthma
6.2 Induction of regulatory T and B cell subsets that can produce immunomodulatory cytokines linked with the prevention of asthma