E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
House dust mite allergic rhinitis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
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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 assess the efficacy of approximately 12 months of SLIT on the Average Adjusted Symptom Score (AASS): a score adjusted according to the daily Rhinitis Total Symptom Scores (RTSSs) and daily rescue medication use, during the increased symptom period.
To document the safety of approximately 12 months of SLIT as well as the safety of a further approximate 12 months Treatment-free Follow-up Phase, during the increased symptom period of both phases (Treatment and Treatment-Free Follow-up Phase)
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of approximately 12 months of SLIT during the increased symptom period on the: Average Rhinitis Total Symptom Score (ARTSS) of the four rhinitis symptoms: sneezing, rhinorrhoea, nasal pruritus and nasal congestion Average Rescue Medication Score (ARMS)(antihistamine[oral and eye drops],nasal corticosteroids and oral corticosteroids). Average Combined Score(ACS)–a score taking into account the Rhinitis Total Symptom Score(RTSS)and Rescue Medication Score(RMS). Five individual Average Symptom Scores(ASS)(sneezing, rhinorrhoea, nasal pruritus, nasal congestion and ocular itching).Proportion of symptom-controlled days(PSCD) Overall Rhinoconjunctivitis QoL Questionnaire(RQLQ) score.Global evaluation of the efficacy of SLIT by the patient.Skin prick test(SPT)specific for house dust mites Immunological markers (IgE and IgG4 specific for house dust mite extract and allergens)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis and Criteria for Inclusion: Inclusion criteria: 1. Male or female outpatients aged 18 to 50 years (inclusive). 2. Patients who have been informed of the nature and aims of the study and have given their written consent to participate in this study in accordance with local laws and requirements. 3. Patients must be in general good health as determined by past medical history, physical examination and safety laboratory tests. 4. Female patients of childbearing potential are eligible if they are not sexually active or if they use a medically accepted contraceptive method. 5. Negative urine pregnancy test on female patients of childbearing potential. 6. House dust mite-related allergic rhinitis for at least 1 year. 7. Sensitised to D. pteronyssinus or D. farinae (positive SPT with wheal diameter greater than 3 mm and a specific IgE level ≥ 0.7 kU/L). 8. Baseline ARTSS ≥5 (after completion of the 7-day daily record card). 9. Patients who are willing to comply with the protocol. 10. Patients who are able to understand the information given and the text of the consent form, and who are able to complete the daily record card and the RQLQ.
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E.4 | Principal exclusion criteria |
Exclusion Criteria: 1. Whatever the considered allergens, co-sensitisation leading to 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). 2. Patients with any nasal condition that could confound the efficacy or safety assessments (for example nasal polyposis). 3. Patients sensitised to cat or dog allergens and living with these animals at home. 4. Pregnant, breast-feeding / lactating or sexually active women of childbearing potential who are not using a medically accepted contraceptive method. 5. Asthma requiring treatment other than beta-2 inhaled agonists. Patients with intermittent asthma not necessitating inhaled or systemic corticoid treatment may be included (corresponding to the Global Initiative for Asthma [GINA] Step 1). 6. Patients treated with systemic, nasal or inhaled steroids (whatever the indication) within 4 weeks before Visit 1. 7. Patients treated with long acting systemic steroids (whatever the indication) within 12 weeks before Visit 1 and before Visit 2. 8. FEV1 < 80% of predicted value at Visit 1. 9. Patients who received allergy specific immunotherapy for house dust mites in the last 10 years. 10. Patients at risk of non-compliance. 11. Participation in any clinical study within the 12 weeks before Visit 1. 12. Investigators, co-investigators, as well as their children or spouses and all the study collaborators should not be enrolled in the study. 13. Any change in environmental measures for allergen avoidance during the study. 14. 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 and endocrine disease. 15. Patients treated with beta-blockers or under continuous corticotherapy. 16. Usual contraindications of immunotherapy such as serious immunopathologic conditions or malignancies. 17. Ongoing treatment by immunotherapy with another allergen. 18. Patients with a history of drug or alcohol abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
Criteria for Evaluation: Primary Efficacy Variable: The primary efficacy variable will be the AASS at endpoint, with endpoint defined as the rhinitis symptom data collected and rescue medication use recorded during the period 01 October 2008 to 31 December 2008 while on treatment. (i.e period of increased symptoms).Adjusted Symptom Score (ASS) is derived as follows: • ASS and RTSS are equal the first day of the period: ASS1 = RTSS1. If a patient did not take rescue medication at days (d-1) and d then: ASSd = RTSSd. If a patient took rescue medication at day d then: ASSd = max (RTSSd, ASSd-1). ASSd+1 = max (RTSSd+1, ASSd). If RTSS is missing, ASS is missing. That is, when a patient takes rescue medication, his / her symptom score will be adjusted the current day and the day after. The ASS ranges from 0 to 12. • For each patient, the AASS will be calculated as the average of the daily (non-missing) ASSs during the period (AASS ranges from 0 to 12). • The AASS will be calculated for each visit period (average of the available and valid daily data) for 1 week after Visit 1 (4 valid days of data are needed in the 7-day period) and each of the 2 weeks after Visit 4, Visit 5 and Visit 6, as well as the average of the available and valid daily data from 01 October 2008 to 31 December 2008. The same principle will apply to Visit 11 to Visit 14, that is, 2 weeks after Visit 11 and Visit 12, as well as the average of the available and valid daily data from 01 October 2009 to 31 December 2009. Data for a given day is valid if the four symptom scores (sneezing, rhinorrhoea, nasal pruritus and nasal congestion) have been recorded appropriately. At least 1 day of data (unless otherwise specified) needs to be valid in a given visit period for the ARTSS to be calculated for the visit period in question. • If no valid data for a given visit period is available, the last observation carried forward (LOCF) approach will be used, if appropriate, to impute the AASS , that is, the AASS from the previous visit period or the baseline AASS if the previous visit period AASS is not available, will be used.
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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) | Yes |
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.8.3 |
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 | 51 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |