Allergic Rhinitis
Conditions
Keywords
House dust mites allergy
Brief summary
The purpose of this study is to assess the efficacy of two doses of sublingual immunotherapy (SLIT) administered as allergen-based tablets once daily over a period of 12 months compared to placebo, for reduction of allergic rhinitis symptoms and rescue medication usage
Detailed description
Allergic rhinitis is a high-prevalence disease in many developed countries, affecting about 10 to 20% of the general population. House dust mite allergens are known to cause perennial allergic rhinitis. In designing the present study, the guidelines proposed by the World Allergy Organization (WAO) task force for methodology of immunotherapy studies have been taken into consideration. After a 2-month screening period, patients will be administered the dose of 300 IR- or 500 IR-house dust mite allergen-based tablets or placebo for a period of 12 months. The carry-over effect will be evaluated after a treatment-free follow up period of 12 months.
Interventions
One sublingual tablet daily for one year
One sublingual tablet daily for one year
DRUGPlacebo tablet
One sublingual tablet daily for one year
Sponsors
Stallergenes Greer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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 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 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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Adjusted Symptom Score (AAdSS) During the Year 1 Primary Period | Last 3 months of Year 1 | The AAdSS is derived from the daily Rhinoconjunctivitis Total Symptom Scores (RTSS), based on the severity of the 4 rhinitis symptoms: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, each graded on a 4-point scale (0-3; 0: absent, 1: mild, 2: moderate, 3: severe). It ranges from 0 to 12, the higher the score the more severe the rhinitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Rhinitis Total Symptom Score (ARTSS) | Last 3 months of Year 1 | The Rhinitis Total Symptom Score (RTSS) evaluates the presence and severity of the 4 rhinitis symptoms: sneezing, rhinorrhoea, nasal pruritus and nasal congestion (absence of symptom (0), mild symptom (1), moderate symptom (2), severe symptom (3)). It ranges from 0 to 12, the higher the score the more severe the rhinitis. |
Participant flow
Recruitment details
First Patient First Visit 12 OCT 2007, Last Patient Last Visit 01 FEB 2010
Participants by arm
| Arm | Count |
|---|---|
| 300 IR 300 IR house dust mites allergen extract tablet | 153 |
| 500 IR 500 IR house dust mites allergen extract tablet | 150 |
| Placebo Placebo tablet | 163 |
| Total | 466 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Year 1 | Adverse Event | 17 | 20 | 5 |
| Year 1 | Any other reason not above-mentioned | 7 | 7 | 6 |
| Year 1 | Withdrawal by Subject | 7 | 7 | 6 |
| Year 2 Follow-up Without Treatment | Adverse Event | 0 | 1 | 1 |
| Year 2 Follow-up Without Treatment | Any other reason not above-mentioned | 5 | 10 | 7 |
| Year 2 Follow-up Without Treatment | Withdrawal by Subject | 1 | 1 | 4 |
Baseline characteristics
| Characteristic | 300 IR | 500 IR | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 29.0 years STANDARD_DEVIATION 8.52 | 30.1 years STANDARD_DEVIATION 8.43 | 30.0 years STANDARD_DEVIATION 8.96 | 29.7 years STANDARD_DEVIATION 8.64 |
| Sex: Female, Male Female | 85 Participants | 77 Participants | 80 Participants | 242 Participants |
| Sex: Female, Male Male | 68 Participants | 73 Participants | 83 Participants | 224 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 128 / 170 | 123 / 169 | 108 / 170 |
| serious Total, serious adverse events | 6 / 170 | 1 / 169 | 2 / 170 |
Outcome results
Primary
Average Adjusted Symptom Score (AAdSS) During the Year 1 Primary Period
The AAdSS is derived from the daily Rhinoconjunctivitis Total Symptom Scores (RTSS), based on the severity of the 4 rhinitis symptoms: sneezing, rhinorrhoea, nasal pruritus and nasal congestion, each graded on a 4-point scale (0-3; 0: absent, 1: mild, 2: moderate, 3: severe). It ranges from 0 to 12, the higher the score the more severe the rhinitis.
Time frame: Last 3 months of Year 1
Population: The Full Analysis Set included all participants who received at least one dose of the investigational product and had at least one Adjusted Symptom Score evaluation in the year.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 300 IR | Average Adjusted Symptom Score (AAdSS) During the Year 1 Primary Period | 3.18 Units on a scale (range: 0 to 12) | Standard Error 0.224 |
| 500 IR | Average Adjusted Symptom Score (AAdSS) During the Year 1 Primary Period | 3.09 Units on a scale (range: 0 to 12) | Standard Error 0.23 |
| Placebo | Average Adjusted Symptom Score (AAdSS) During the Year 1 Primary Period | 3.87 Units on a scale (range: 0 to 12) | Standard Error 0.217 |
p-value: 0.0066ANCOVA
p-value: 0.015ANCOVA
Secondary
Average Rhinitis Total Symptom Score (ARTSS)
The Rhinitis Total Symptom Score (RTSS) evaluates the presence and severity of the 4 rhinitis symptoms: sneezing, rhinorrhoea, nasal pruritus and nasal congestion (absence of symptom (0), mild symptom (1), moderate symptom (2), severe symptom (3)). It ranges from 0 to 12, the higher the score the more severe the rhinitis.
Time frame: Last 3 months of Year 1
Population: The Full Analysis Set included all participants who received at least one dose of the investigational product and had at least one Adjusted Symptom Score evaluation in the year.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 300 IR | Average Rhinitis Total Symptom Score (ARTSS) | 2.74 Units on a scale (range: 0 to 12) | Standard Error 0.178 |
| 500 IR | Average Rhinitis Total Symptom Score (ARTSS) | 2.72 Units on a scale (range: 0 to 12) | Standard Error 0.183 |
| Placebo | Average Rhinitis Total Symptom Score (ARTSS) | 3.32 Units on a scale (range: 0 to 12) | Standard Error 0.173 |
p-value: 0.0086ANCOVA
p-value: 0.0095ANCOVA