House Dust Mite Allergic Rhinitis MedDRA version: 14.1 Level: LLT Classification code 10001723 Term: Allergic rhinitis System Organ Class: 100000004855
Conditions
Interventions
Product Name: Sublingual tablet of HDM Allergen Extracts
Pharmaceutical Form: Sublingual tablet
Other descriptive name: Dermatophagoides pteronyssinus allergen extract
Concentration unit: BAU/ml Bioeq
Sponsors
Stallergenes S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female outpatients, aged 5-17 years inclusive 2. History of house dust mite-related allergic rhinitis for at least 1 year requiring regular intake of symptomatic treatment(s) 3. Sensitised to D. pteronyssinus and/or D. farinae (positive skin prick test with wheal diameter greater than 3 mm and a specific IgE level = 0.7 kU/L) 4. Baseline ARTSS = 5 after completion of the 7-day daily record card with at least 4 days of valid data 5. General good condition as determined by past medical history, physical examination and safety laboratory tests 6. Negative urine pregnancy test on all female patients who have had their menarche 7. Patients and/or legal representative who are willing to comply with the protocol 8. Patients and/or legal representative who are able to understand the information given and the text of the consent form, who are able to complete the daily record card and the RQLQ; patients who are able to understand the information of the RQLQ given by the interviewer (applicable only from 6 years on) 9. Patient and/or legal representative having given his signed informed consent. 10. Patient registered with the French Social Security System (for France only) Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Co-sensitization associated with clinically relevant allergic rhinitis, sinusitis, conjunctivitis or asthma likely to significantly change the symptoms of the patient throughout the study (that means patient symptomatic to another allergen than house dust mites to which the patient will be exposed during the study; i.e. will notably be excluded - patients sensitised to cat or dog allergens and regularly exposed to these allergens - patients sensitised to aspergillus, cladosporium, alternaria - patients sensitised to parietaria , ragweed, or mugwort, if this allergen is endemic to the region 2. Patients with any nasal or oral condition that could confound the efficacy or safety assessments such as nasal polyposis, chronic sinusitis or oral inflammation (for example oral lichen planus, oral ulceration or oral mycosis). 3. Patients with moderate or severe persistent asthma (GINA 3 or 4) 4. Patients with mild persistent asthma (GINA 2) necessitating treatment with inhaled glucocorticosteroids at a daily dose level greater than 400 mcg budesonide dose-equivalents [that is, patients with GINA 1 asthma or asthmatic patients necessitating treatment with inhaled corticosteroids at a daily dose level equal to or less than 400 mcg budesonide dose-equivalents at stable dose in the last 4 weeks may be included in the study] 5. FEV1 < 80% of predicted value at visit V1 6. Any change in environmental measures for allergen avoidance during the study. 7. Patients treated with systemic steroids (whatever the indication) within 4 weeks before visit V1. 8. Patients treated with long acting systemic steroids (whatever the indication) within 12 weeks before visit V1 or between visits V1 and V2. 9. Patients treated with beta-blockers or continuous corticotherapy, other than a daily dose level equal to or less than 400 mcg of inhaled budesonide dose-equivalents for asthmatic patients. 10. Patients treated with antihistamines for any reasons other than house dust mite allergic rhinitis symptoms 11. Patients who received allergen specific immunotherapy for house dust mites in the last 5 years. 12. Ongoing immunotherapy with any allergen. 13. Patients with a past or current disease, which as judged by the investigator, may affect the patient's participation in or the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, immunological disease, psychiatric disease, dermatological disease, and endocrine disease. 14. Usual contraindications of immunotherapy such as serious immunopathologic conditions or malignancies. 15. Intolerance to any excipients (more specifically to lactose) 16. Patients with a history of drug or alcohol abuse. 17. Pregnant or breast-feeding women 18. Sexually active female patients of childbearing potential who are not willing to use a medically accepted contraceptive method until the end of the study(hormonal birth control [orally, injectable or by implant, for at least 2 months before enrolment], bilateral tubal ligation, monogamous relationship with a vasectomised partner) 19. Patients likely to be non-compliant 20. Patients who have already been included in this study or who are participating in another study 21. Patients having participated in a study with an investigational drug in the 12 weeks preceding V1 22. Children of Investigators, co-investigators and of all the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if sublingual tablet of HDM Allergen Extracts administered at a dosage of 300 IR to children and adolescents during approximately 12 months, is significantly better than placebo in relieving house dust mite allergic rhinitis symptoms, as assessed by the magnitude of response observed on the Average Adjusted Symptom Score (AAdSS). The AAdSS is a score assessing four rhinitis symptoms: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, adjusted on the rescue medication intake. Sustained Treatment efficacy objective: To assess the sustained clinical efficacy of 300 IR sublingual tablet of HDM Allergen Extracts on the AAdSS after two and three treatment years. Post-treatment long-term efficacy objective: To assess the post treatment long-term efficacy (disease modifying effect) of 300IR sublingual tablet of HDM Allergen Extracts on the AAdSS after one and two treatment-free years. ;Secondary Objective: To assess treatment sustained clinical efficacy after 1 treatment year & post treatment long-term efficacy of 300IR in rhinitis overall & overtime, assessed on different global or individual scores, improvement in allergic rhinitis life impact, & safety on: o Average Adjusted Symptom Score (AAdSS) by tertile o Average Adjusted Symptom Score (AAdSS) at different periods o Average Rhinitis Total Symptom Score of 4 rhinitis symptoms o Average Rescue Medication Score o Each of 5 individual Average Rhinoconjunctivitis Symptom Score o Onset action of SLIT o Rescue medication usage o Average Combined Score – score combining Rhinitis Total Symptom Score & Rescue medication score. o Overall Rhinoconjunctivitis Quality of Life Questionnaire score. o Proportion of symptom-controlled days (PSCD) o The Proportion of Not-Controlled Days (PNCD) o The onset of action of SLIT o Safety of treatment ;Primary end point(s): The primary efficacy criterion is the Average Adjusted Symptom Score (AAdSS), during the primary period of the acti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy criterion • AAdSS during the other periods of the trial • The Average Rhinitis Total Symptom Score (ARTSS) • The Average Rescue Medication Score (ARMS) • Five individual Average Rhinoconjunctivitis Symptom Scores (ARSS) • Proportion of patients using rescue medication will be calculated for the periods of assessment. • Proportion of days patients use rescue medication will be calculated for the periods of assessment. • Average Combined Score (ACS). • Proportion of Symptom-controlled Days (PSCD). • Overall Rhinoconjunctivitis Quality of Life Questionnaire • Onset of action of SLIT Exploratory criteria • Global evaluation of allergic rhinitis by the patient using a VAS score (0-10 cm) • Asthma evaluation (Status: present/absent; classification using GINA; asthma-related lower airway symptoms (cough, wheezing, chest tightness and breathlessness)) • Nasal provocation test in patients from some selected sites (the nasal provocation test will not be proposed to patients who are only sensitised to D. Farinae) at Visit 2 and Visit 7 only. Other Criteria • Wheal diameters after Skin Prick Tests (SPT) to mites allergens • Immunological markers: (IgE, IgG4, IgA) specific for house dust mite extracts and Der p 1, Der p 2, Der p 10, Der f 1 and Der f 2 allergens (list not exhaustive) • Circulating house dust mite-specific CD4+ T-cell responses in a sub-group of at least 50 children • Sensitisation status Safety • Occurrence of adverse events • Routine haematology and biochemistry ;Timepoint(s) of evaluation of this end point: 12 months. | — |
Countries
Denmark, France, Germany, Hungary, Ireland, Romania, Slovakia, Spain, Ukraine
Outcome results
None listed