Allergic Rhinitis Due to House Dust Mite
Conditions
Keywords
HDM, allergic rhinitis
Brief summary
The purpose of this study is to assess the effect of 3 doses of sublingual house dust mite (HDM) tablets versus placebo in the change from baseline of rhinitis total symptom score during the allergen chamber challenge before and after 6 months of treatment.
Interventions
DRUG100 IR house dust mites allergen extract tablet
One sublingual tablet daily during 6 months
One sublingual tablet daily during 6 months
One sublingual tablet daily during 6 months
DRUGPlacebo tablet
One sublingual tablet daily during 6 months
Sponsors
Stallergenes Greer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* history of HDM rhinitis allergy for \> 1 year * sensitized to D. pteronyssinus and/or D. farinae * RTSS \>= 6 at least 2 time points during allergen challenge session
Exclusion criteria
* co sensitization to other allergen than HDM * FEV1 \< 80% * Asthma GINA \> 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge | 6 months | The primary efficacy endpoint was the change from baseline (ChBL) (that is the first allergen challenge before treatment initiation) to the end-of-treatment period (6 months) in the Area Under the Curve (AUC) of the Rhinitis Total Symptom Score (RTSS) recorded during the four hours of the allergen challenge in the Environmental Exposure Chamber (EEC). The RTSS is the sum of four individual nasal symptom scores (rhinorrhoea, nasal congestion, nasal pruritus and sneezing), each assessed on a 0-3 rating scale. The RTSS was evaluated every 15 minutes in the first 2 hours and every 30 minutes in the last two hours, i.e. at 13 timepoints during each allergen challenge (from T0 to T240), and the scores were plotted against time (0 to 4 hours) to calculate the area under the curve, AUCRTSS\_0-4h. A decrease in the AUCRTSS\_0-4h value represents relief from the HDM allergic symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge | 6 months | Change from baseline (ChBL) (that is the first allergen challenge before treatment initiation) to the end-of-treatment period (6 months) in the Area Under the Curve (AUC) of the Rhinitis Total Symptom Score (RTSS) recorded during the last two hours (2-4h) of the allergen challenge in the Environmental Exposure Chamber (EEC). The RTSS is the sum of four individual nasal symptom scores (rhinorrhoea, nasal congestion, nasal pruritus and sneezing), each assessed on a 0-3 rating scale. |
Countries
Canada
Participant flow
Recruitment details
First Patient First Visit 08 DEC 2010, Last Patient Last Visit 19 SEP 2012
Participants by arm
| Arm | Count |
|---|---|
| 100 IR 100 IR house dust mites allergen extract tablet | 89 |
| 300 IR 300 IR house dust mites allergen extract tablet | 86 |
| 500 IR 500 IR house dust mites allergen extract tablet | 93 |
| Placebo Placebo tablet | 87 |
| Total | 355 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 5 | 11 | 0 |
| Overall Study | Any other reason not above-mentioned | 6 | 7 | 8 | 8 |
| Overall Study | Withdrawal by Subject | 3 | 6 | 4 | 4 |
Baseline characteristics
| Characteristic | 100 IR | 300 IR | 500 IR | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.43 years STANDARD_DEVIATION 10.089 | 32.53 years STANDARD_DEVIATION 8.558 | 32.76 years STANDARD_DEVIATION 9.327 | 31.25 years STANDARD_DEVIATION 8.753 | 32.25 years STANDARD_DEVIATION 9.19 |
| Sex: Female, Male Female | 47 Participants | 45 Participants | 44 Participants | 47 Participants | 183 Participants |
| Sex: Female, Male Male | 42 Participants | 41 Participants | 49 Participants | 40 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 82 / 89 | 73 / 86 | 81 / 93 | 71 / 87 |
| serious Total, serious adverse events | 1 / 89 | 1 / 86 | 2 / 93 | 0 / 87 |
Outcome results
Primary
Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge
The primary efficacy endpoint was the change from baseline (ChBL) (that is the first allergen challenge before treatment initiation) to the end-of-treatment period (6 months) in the Area Under the Curve (AUC) of the Rhinitis Total Symptom Score (RTSS) recorded during the four hours of the allergen challenge in the Environmental Exposure Chamber (EEC). The RTSS is the sum of four individual nasal symptom scores (rhinorrhoea, nasal congestion, nasal pruritus and sneezing), each assessed on a 0-3 rating scale. The RTSS was evaluated every 15 minutes in the first 2 hours and every 30 minutes in the last two hours, i.e. at 13 timepoints during each allergen challenge (from T0 to T240), and the scores were plotted against time (0 to 4 hours) to calculate the area under the curve, AUCRTSS\_0-4h. A decrease in the AUCRTSS\_0-4h value represents relief from the HDM allergic symptoms.
Time frame: 6 months
Population: Full Analysis Set (FAS): all patients who received at least one dose of the investigational product.~(Number of patients at Visit 7 for whom data is available).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 100 IR | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge | -715.83 RTSS * hour | Standard Error 67.261 |
| 300 IR | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge | -769.21 RTSS * hour | Standard Error 70.659 |
| 500 IR | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge | -795.58 RTSS * hour | Standard Error 69.877 |
| Placebo | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 4 Hours (0-4h) of the Allergen Challenge | -597.40 RTSS * hour | Standard Error 67.401 |
p-value: 0.042795% CI: [-389.82, -6.55]ANCOVA
p-value: 0.079395% CI: [-363.87, 20.24]ANCOVA
Comparison: The statistical test is not applicable due to the step-down approach performed to address the multiplicity issue.95% CI: [-305.9, 69.04]ANCOVA
Secondary
Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge
Change from baseline (ChBL) (that is the first allergen challenge before treatment initiation) to the end-of-treatment period (6 months) in the Area Under the Curve (AUC) of the Rhinitis Total Symptom Score (RTSS) recorded during the last two hours (2-4h) of the allergen challenge in the Environmental Exposure Chamber (EEC). The RTSS is the sum of four individual nasal symptom scores (rhinorrhoea, nasal congestion, nasal pruritus and sneezing), each assessed on a 0-3 rating scale.
Time frame: 6 months
Population: Full Analysis Set (FAS): all patients who received at least one dose of the investigational product
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 100 IR | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge | -390.34 RTSS * hour | Standard Error 40.355 |
| 300 IR | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge | -421.39 RTSS * hour | Standard Error 42.4 |
| 500 IR | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge | -424.77 RTSS * hour | Standard Error 41.89 |
| Placebo | Change From Baseline to the End-of-treatment Period in the Area Under the Curve of the Rhinitis Total Symptom Score Recorded During 2 Hours (2-4h) of the Allergen Challenge | -299.16 RTSS * hour | Standard Error 40.43 |
p-value: 0.032395% CI: [-240.53, -10.69]ANCOVA
p-value: 0.037695% CI: [-237.38, -7.08]ANCOVA
p-value: 0.111995% CI: [-203.74, 21.38]ANCOVA