Allergic Rhinitis Due to Dermatophagoides Farinae, Allergic Rhinitis Due to Dermatophagoides Pteronyssinus, Allergic Rhinitis Due to House Dust Mite
Conditions
Keywords
Allergic rhinitis, HDM, pediatric
Brief summary
A research study of how house dust mite tablets work compared to placebo in children aged between 5 and 11 years and who have allergy to house dust mites (MATIC)
Detailed description
The trial aims to demonstrate efficacy of the House Dust Mite SLIT-tablet compared to placebo in children (5-11 years of age) with House Dust Mite allergic rhinitis based on the total combined rhinitis symptoms and medication score during the last 8 weeks of treatment. In addition, the trial will evaluate safety and tolerability of the treatment, and assess whether treatment has an impact on asthma symptoms and medication use, immunological parameters, and rhinoconjunctivitis quality of life (QoL). The trial is a randomised, parallel-group, double-blind, placebo-controlled multi-national phase III trial conducted in Europe and North America. The treatment period will be approximately 1 year.
Interventions
BIOLOGICALSublingual allergy immunotherapy tablet
For daily administration (1 tablet per day)
OTHERPlacebo
For daily administration (1 tablet per day)
Sponsors
ALK-Abelló A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects aged 5-11 years * A clinical history of HDM AR/C (Allergic rhinitis/rhinoconjunctivitis) (with or without asthma) and with allergic rhinitis symptoms despite having received allergy pharmacotherapy during the previous year prior to screening * Have a certain level of AR (Allergic rhinitis) symptoms on at least 8 of the last 14 days of the baseline period * Use symptomatic medication for treatment of HDM allergic rhinitis during at least 8 of the last 14 days of the baseline period * Positive skin prick test (SPT) and IgE (Immunoglobulin E) to D. pteronyssinus or D. farinae at screening * Lung function ≥ 70% of predicted value
Exclusion criteria
* Sensitised and regularly exposed to perennial allergens * Any nasal or pharyngeal condition that could interfere with the safety or efficacy evaluation * Asthma requiring treatment with high dose of inhaled corticosteroid * A relevant history of systemic allergic reaction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Total Combined Rhinitis Symptom and Medication Score (TCRS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The primary endpoint in the trial was the average daily total combined rhinitis symptoms and medication score (TCRS) during the primary efficacy assessment period. The average daily TCRS evaluates the treatment effect based on the reduction in daily rhinitis symptoms and medication score (on a scale of 0-24). Higher scores indicate more severe symptoms and/or more use of rhinitis medication. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 daily TCRS values, the primary endpoint is calculated as the average of those values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Average Rhinitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | Average rhinitis DMS evaluates the treatment effect based on the reduction in daily rhinitis medication use (on a scale of 0-12). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis DMS values, the endpoint is calculated as the average of those values. |
| The Average Daily Total Combined Rhinoconjunctivitis Symptom and Medication Score (TCS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | Average rhinoconjunctivitis TCS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 daily TCS values, the endpoint is calculated as the average of those values. |
| The Average Rhinoconjunctivitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The average rhinoconjunctivitis DSS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptom score (on a scale of 0-18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis DSS values, the endpoint is calculated as the average of those values. |
| The Average Rhinoconjunctivitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | Average rhinoconjunctivitis DMS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0-20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis DMS values, the endpoint is calculated as the average of those values. |
| Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score at the End of Trial | Week leading up to visit 7 (at the end of the primary efficacy assessment period, after approximately 52-57 weeks of treatment) | The overall PRQLQ score measures the effect of rhinoconjunctivitis on participant's quality of life on a scale of 0-6. Higher scores indicate worse rhinoconjunctivitis-related quality of life. |
| The Average Asthma Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The average asthma DSS evaluates the treatment effect based on the reduction in daily asthma symptom score (on a scale of 0-12). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 asthma DSS values, the endpoint is calculated as the average of those values. |
| SABA Free Days During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The endpoint SABA free days evaluates the treatment effect based on the reduction in SABA use. The higher the proportion of SABA free days the higher the estimated probability of a participant having a day where they didn't use SABA. |
| Weekly Number of Puffs of As-needed SABA Use During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | Average weekly number of puffs of as-needed SABA use evaluates the treatment effect based on the reduction in the use of asthma reliever medication (SABA), and is calculated as 7 times the average of the daily number of puffs of as-needed SABA use. Higher values indicate more medication use. |
| The Average Rhinitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The average rhinitis DSS evaluates the treatment effect based on the reduction in daily rhinitis symptom score (on a scale of 0-12). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis DSS values, the endpoint is calculated as the average of those values. |
| Rhinitis Exacerbation Days During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The endpoint rhinitis exacerbation days evaluates the treatment effect based on days when participants have severe symptoms. The higher the proportion of rhinitis mild days the higher the estimated probability of a participant having a rhinitis exacerbation day. |
| Average Rhinitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | Average rhinitis CSMS evaluates the treatment effect based on the reduction in daily rhinitis symptoms and/or medication use. For this endpoint, the rhinitis symptoms and medication use were scored using an alternative method as recommended by EAACI (European Academy of Allergy & Clinical Immunology) (on a scale of 0-5). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis CSMS values, the endpoint is calculated as the average of those values. |
| Average Rhinoconjunctivitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | Average rhinoconjunctivitis CSMS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms and/or medication use. For this endpoint, the rhinoconjunctivitis symptoms and medication use were scored using an alternative method as recommended by EAACI (European Academy of Allergy & Clinical Immunology) (on a scale of 0-5). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis CSMS values, the endpoint is calculated as the average of those values. |
| House Dust Mite Specific IgE | Change from screening to the end of trial (after approximately 52-57 weeks of treatment) | House dust mite specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation |
| House Dust Mite Specific IgG4 | Change from screening to the end of trial (after approximately 52-57 weeks of treatment) | House dust mite specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation |
| Total IgE | Change from screening to the end of trial (after approximately 52-57 weeks of treatment) | The change in total IgE was measured from screening to the end of trial. |
| House Dust Mite IgE-Blocking Factor | Change from screening to the end of trial (after approximately 52-57 weeks of treatment) | The IgE-blocking factor assesses the effect of serum components (including IgE-blocing antibodies known to be induced by allergy immunotherapy) competing with IgE for binding to allergen. IgE-blocking factor is calculated as 1-(S/T), where S is the amount of allergen-specific IgE bound to allergen in the (possible) presence of competing components, and where T is the total amount of allergen-specific IgE capable of binding to allergen when all competing antibodies/components have been washed off. IgE-blocking factor values closer to 0 indicate the presence of fewer IgE-blocking components and values closer to 1 indicate that more IgE is blocked from binding to the allergen. |
| Rhinitis Mild Days During the Primary Efficacy Assessment Period | 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP | The endpoint rhinitis mild days evaluates the treatment effect based on days when participants have no symptoms or mild symptoms and no medication use. The higher the proportion of rhinitis mild days the higher the estimated probability of a participant having a rhinitis mild day. |
Countries
Bulgaria, Canada, France, Germany, Lithuania, Poland, Russia, Slovakia, Spain, Ukraine, United States
Participant flow
Recruitment details
The trial randomized 1460 participants from 95 sites in 11 countries (Bulgaria, Canada, France, Germany, Lithuania, Poland, Russia, Slovakia, Spain, Ukraine, United States).
Pre-assignment details
The trial randomized 1460 participants. Two participants in the 12 SQ-HDM group were randomized in error and did not receive study treatment, hence the number of participants that started (who were randomized and treated) is 1458.
Participants by arm
| Arm | Count |
|---|---|
| HDM SLIT-tablet (12 SQ-HDM) Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose). | 727 |
| Placebo SLIT-tablet Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet). | 731 |
| Total | 1,458 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 6 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Reason stated as 'Other' in the case report form (CRF) | 7 | 7 |
| Overall Study | Withdrawal by Subject | 12 | 8 |
Baseline characteristics
| Characteristic | Total | HDM SLIT-tablet (12 SQ-HDM) | Placebo SLIT-tablet |
|---|---|---|---|
| Age, Continuous | 8.0 years STANDARD_DEVIATION 1.9 | 8.0 years STANDARD_DEVIATION 1.9 | 8.0 years STANDARD_DEVIATION 1.9 |
| Allergy history | 1457 Participants | 726 Participants | 731 Participants |
| Asthma status at baseline ICS use | 308 Participants | 148 Participants | 160 Participants |
| Asthma status at baseline Reported asthma | 557 Participants | 267 Participants | 290 Participants |
| Baseline sensitisations House dust mite and others | 761 Participants | 390 Participants | 371 Participants |
| Baseline sensitisations House dust mite only | 697 Participants | 337 Participants | 360 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 26 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1385 Participants | 688 Participants | 697 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 28 Participants | 13 Participants | 15 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 5 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Multiple | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 8 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Race White | 1436 Participants | 722 Participants | 714 Participants |
| Region of Enrollment Bulgaria | 181 participants | 91 participants | 90 participants |
| Region of Enrollment Canada | 38 participants | 18 participants | 20 participants |
| Region of Enrollment France | 3 participants | 2 participants | 1 participants |
| Region of Enrollment Germany | 17 participants | 8 participants | 9 participants |
| Region of Enrollment Lithuania | 94 participants | 47 participants | 47 participants |
| Region of Enrollment Poland | 353 participants | 176 participants | 177 participants |
| Region of Enrollment Russia | 329 participants | 163 participants | 166 participants |
| Region of Enrollment Slovakia | 66 participants | 33 participants | 33 participants |
| Region of Enrollment Spain | 7 participants | 3 participants | 4 participants |
| Region of Enrollment Ukraine | 330 participants | 165 participants | 165 participants |
| Region of Enrollment United States | 40 participants | 21 participants | 19 participants |
| Sex: Female, Male Female | 495 Participants | 241 Participants | 254 Participants |
| Sex: Female, Male Male | 963 Participants | 486 Participants | 477 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 727 | 0 / 731 |
| other Total, other adverse events | 608 / 727 | 534 / 731 |
| serious Total, serious adverse events | 16 / 727 | 6 / 731 |
Outcome results
Primary
Average Daily Total Combined Rhinitis Symptom and Medication Score (TCRS) During the Primary Efficacy Assessment Period
The primary endpoint in the trial was the average daily total combined rhinitis symptoms and medication score (TCRS) during the primary efficacy assessment period. The average daily TCRS evaluates the treatment effect based on the reduction in daily rhinitis symptoms and medication score (on a scale of 0-24). Higher scores indicate more severe symptoms and/or more use of rhinitis medication. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 daily TCRS values, the primary endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Average Daily Total Combined Rhinitis Symptom and Medication Score (TCRS) During the Primary Efficacy Assessment Period | 3.4 score on a scale | Standard Error 0.3 |
| Placebo SLIT-tablet | Average Daily Total Combined Rhinitis Symptom and Medication Score (TCRS) During the Primary Efficacy Assessment Period | 4.4 score on a scale | Standard Error 0.3 |
Comparison: The average daily TCRS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: <0.000195% CI: [0.5, 1.4]Mixed Models Analysis
Secondary
Average Rhinitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period
Average rhinitis CSMS evaluates the treatment effect based on the reduction in daily rhinitis symptoms and/or medication use. For this endpoint, the rhinitis symptoms and medication use were scored using an alternative method as recommended by EAACI (European Academy of Allergy & Clinical Immunology) (on a scale of 0-5). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis CSMS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Average Rhinitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period | 0.8 score on a scale | Standard Error 0.1 |
| Placebo SLIT-tablet | Average Rhinitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period | 1.0 score on a scale | Standard Error 0.1 |
Comparison: The average rhinitis CSMS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: <0.000195% CI: [0.1, 0.3]Mixed Models Analysis
Secondary
Average Rhinoconjunctivitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period
Average rhinoconjunctivitis CSMS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms and/or medication use. For this endpoint, the rhinoconjunctivitis symptoms and medication use were scored using an alternative method as recommended by EAACI (European Academy of Allergy & Clinical Immunology) (on a scale of 0-5). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis CSMS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Average Rhinoconjunctivitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period | 0.7 score on a scale | Standard Error 0.1 |
| Placebo SLIT-tablet | Average Rhinoconjunctivitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period | 0.9 score on a scale | Standard Error 0.1 |
Comparison: The average rhinoconjunctivitis CSMS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: <0.000195% CI: [0.1, 0.3]Mixed Models Analysis
Secondary
House Dust Mite IgE-Blocking Factor
The IgE-blocking factor assesses the effect of serum components (including IgE-blocing antibodies known to be induced by allergy immunotherapy) competing with IgE for binding to allergen. IgE-blocking factor is calculated as 1-(S/T), where S is the amount of allergen-specific IgE bound to allergen in the (possible) presence of competing components, and where T is the total amount of allergen-specific IgE capable of binding to allergen when all competing antibodies/components have been washed off. IgE-blocking factor values closer to 0 indicate the presence of fewer IgE-blocking components and values closer to 1 indicate that more IgE is blocked from binding to the allergen.
Time frame: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)
Population: Participants from Canada and Poland in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | House Dust Mite IgE-Blocking Factor | 0.4 unitless | Standard Deviation 0.3 |
| Placebo SLIT-tablet | House Dust Mite IgE-Blocking Factor | -0.0 unitless | Standard Deviation 0.1 |
Secondary
House Dust Mite Specific IgE
House dust mite specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation
Time frame: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)
Population: Participants from Canada and Poland in the full analysis set with observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | House Dust Mite Specific IgE | Dermatophagoides pteronyssinus specific IgE | 0.2 log10 transformed kU/L | Standard Deviation 0.3 |
| HDM SLIT-tablet (12 SQ-HDM) | House Dust Mite Specific IgE | Dermatophagoides farinae specific IgE | 0.3 log10 transformed kU/L | Standard Deviation 0.3 |
| Placebo SLIT-tablet | House Dust Mite Specific IgE | Dermatophagoides pteronyssinus specific IgE | 0.0 log10 transformed kU/L | Standard Deviation 0.2 |
| Placebo SLIT-tablet | House Dust Mite Specific IgE | Dermatophagoides farinae specific IgE | 0.0 log10 transformed kU/L | Standard Deviation 0.2 |
Secondary
House Dust Mite Specific IgG4
House dust mite specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation
Time frame: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)
Population: Participants from Canada and Poland in the full analysis set with observations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | House Dust Mite Specific IgG4 | Dermatophagoides farinae specific IgG4 | 0.7 log10 transformed mg/L | Standard Deviation 0.4 |
| HDM SLIT-tablet (12 SQ-HDM) | House Dust Mite Specific IgG4 | Dermatophagoides pteronyssinus specific IgG4 | 0.6 log10 transformed mg/L | Standard Deviation 0.4 |
| Placebo SLIT-tablet | House Dust Mite Specific IgG4 | Dermatophagoides pteronyssinus specific IgG4 | 0.0 log10 transformed mg/L | Standard Deviation 0.1 |
| Placebo SLIT-tablet | House Dust Mite Specific IgG4 | Dermatophagoides farinae specific IgG4 | 0.0 log10 transformed mg/L | Standard Deviation 0.2 |
Secondary
Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score at the End of Trial
The overall PRQLQ score measures the effect of rhinoconjunctivitis on participant's quality of life on a scale of 0-6. Higher scores indicate worse rhinoconjunctivitis-related quality of life.
Time frame: Week leading up to visit 7 (at the end of the primary efficacy assessment period, after approximately 52-57 weeks of treatment)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score at the End of Trial | 0.8 score on a scale | Standard Error 0.1 |
| Placebo SLIT-tablet | Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score at the End of Trial | 1.0 score on a scale | Standard Error 0.1 |
Comparison: The overall PRQLQ score was analysed using a linear mixed effect (LME) model. The model includes the overall PRQLQ score as response variable, treatment and cohort as fixed factors, the baseline overall PRQLQ score as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: <0.000195% CI: [0.1, 0.2]Mixed Models Analysis
Secondary
Rhinitis Exacerbation Days During the Primary Efficacy Assessment Period
The endpoint rhinitis exacerbation days evaluates the treatment effect based on days when participants have severe symptoms. The higher the proportion of rhinitis mild days the higher the estimated probability of a participant having a rhinitis exacerbation day.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Rhinitis Exacerbation Days During the Primary Efficacy Assessment Period | 2.5 Probability (%) of a rhinitis exace. day |
| Placebo SLIT-tablet | Rhinitis Exacerbation Days During the Primary Efficacy Assessment Period | 4.4 Probability (%) of a rhinitis exace. day |
Comparison: The odds of having a rhinitis exacerbation day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model included the endpoint (yes/no) as response variable, treatment and cohort as fixed effects, the baseline average rhinitis DSS as a covariate, the combined (country/region) variable within cohort and subject as random effects. Proportion is the estimated probability of having a rhinitis exacerbation day, odds ratio is (odds 12 SQ-HDM / odds Placebo).p-value: <0.000195% CI: [0.4, 0.7]Generalised linear mixed model (GLMM)
Secondary
Rhinitis Mild Days During the Primary Efficacy Assessment Period
The endpoint rhinitis mild days evaluates the treatment effect based on days when participants have no symptoms or mild symptoms and no medication use. The higher the proportion of rhinitis mild days the higher the estimated probability of a participant having a rhinitis mild day.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants with asthma in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Rhinitis Mild Days During the Primary Efficacy Assessment Period | 31.8 Probability (%) of a rhinitis mild day |
| Placebo SLIT-tablet | Rhinitis Mild Days During the Primary Efficacy Assessment Period | 20.9 Probability (%) of a rhinitis mild day |
Comparison: The odds of having a rhinitis mild day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model included the endpoint (yes/no) as response variable, treatment and cohort as fixed effects, the baseline average rhinitis TCRS as a covariate, the combined (country/region) variable within cohort and subject as random effects. Proportion is the estimated probability of having a day with no or mild rhinitis symptoms, odds ratio is (odds 12 SQ-HDM / odds Placebo).p-value: 0.000895% CI: [1.3, 2.5]Generalised linear mixed model (GLMM)
Secondary
SABA Free Days During the Primary Efficacy Assessment Period
The endpoint SABA free days evaluates the treatment effect based on the reduction in SABA use. The higher the proportion of SABA free days the higher the estimated probability of a participant having a day where they didn't use SABA.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants with asthma in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | SABA Free Days During the Primary Efficacy Assessment Period | 99.2 Probability (%) of a SABA free day |
| Placebo SLIT-tablet | SABA Free Days During the Primary Efficacy Assessment Period | 98.6 Probability (%) of a SABA free day |
Comparison: The odds of having a SABA free day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model included SABA free day (yes/no) as response variable, treatment and cohort as fixed effects, the baseline average asthma DSS as a covariate, the combined (country/region) variable within cohort and subject as random effects. Proportion is the estimated probability of having a day where a subject with asthma did not use SABA, odds ratio is (odds active/odds Placebo).p-value: 0.052795% CI: [1, 3.3]Generalised linear mixed model (GLMM)
Secondary
The Average Asthma Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period
The average asthma DSS evaluates the treatment effect based on the reduction in daily asthma symptom score (on a scale of 0-12). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 asthma DSS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants with asthma in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | The Average Asthma Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 0.3 score on a scale | Standard Error 0 |
| Placebo SLIT-tablet | The Average Asthma Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 0.4 score on a scale | Standard Error 0 |
Comparison: The average asthma DSS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: 0.025995% CI: [0, 0.2]Mixed Models Analysis
Secondary
The Average Daily Total Combined Rhinoconjunctivitis Symptom and Medication Score (TCS) During the Primary Efficacy Assessment Period
Average rhinoconjunctivitis TCS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 daily TCS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | The Average Daily Total Combined Rhinoconjunctivitis Symptom and Medication Score (TCS) During the Primary Efficacy Assessment Period | 4.0 score on a scale | Standard Error 0.4 |
| Placebo SLIT-tablet | The Average Daily Total Combined Rhinoconjunctivitis Symptom and Medication Score (TCS) During the Primary Efficacy Assessment Period | 5.2 score on a scale | Standard Error 0.4 |
p-value: <0.000195% CI: [0.6, 1.7]Mixed Models Analysis
Secondary
The Average Rhinitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period
Average rhinitis DMS evaluates the treatment effect based on the reduction in daily rhinitis medication use (on a scale of 0-12). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis DMS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | The Average Rhinitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period | 1.4 score on a scale | Standard Error 0.2 |
| Placebo SLIT-tablet | The Average Rhinitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period | 1.9 score on a scale | Standard Error 0.2 |
Comparison: The average rhinitis DMS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: 0.001695% CI: [0.2, 0.8]Mixed Models Analysis
Secondary
The Average Rhinitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period
The average rhinitis DSS evaluates the treatment effect based on the reduction in daily rhinitis symptom score (on a scale of 0-12). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis DSS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | The Average Rhinitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 1.5 score on a scale | Standard Error 0.1 |
| Placebo SLIT-tablet | The Average Rhinitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 1.9 score on a scale | Standard Error 0.1 |
Comparison: The average rhinitis DSS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: <0.000195% CI: [0.2, 0.6]Mixed Models Analysis
Secondary
The Average Rhinoconjunctivitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period
Average rhinoconjunctivitis DMS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0-20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis DMS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | The Average Rhinoconjunctivitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period | 1.8 score on a scale | Standard Error 0.2 |
| Placebo SLIT-tablet | The Average Rhinoconjunctivitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period | 2.4 score on a scale | Standard Error 0.3 |
Comparison: The average rhinoconjunctivitis DMS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: 0.001895% CI: [0.2, 1]Mixed Models Analysis
Secondary
The Average Rhinoconjunctivitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period
The average rhinoconjunctivitis DSS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptom score (on a scale of 0-18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis DSS values, the endpoint is calculated as the average of those values.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants in the full analysis set with observations in the primary efficacy period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | The Average Rhinoconjunctivitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 1.7 score on a scale | Standard Error 0.1 |
| Placebo SLIT-tablet | The Average Rhinoconjunctivitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period | 2.2 score on a scale | Standard Error 0.2 |
Comparison: The average rhinoconjunctivitis DSS was analysed using a linear mixed effect (LME) model with square root transformation. The model includes the square root of the endpoint as response variable, treatment and cohort as fixed factors, the square root of the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: <0.000195% CI: [0.3, 0.7]Mixed Models Analysis
Secondary
Total IgE
The change in total IgE was measured from screening to the end of trial.
Time frame: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)
Population: Participants from Canada and Poland in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Total IgE | 0.2 log10 transformed kU/L | Standard Deviation 0.3 |
| Placebo SLIT-tablet | Total IgE | 0.0 log10 transformed kU/L | Standard Deviation 0.2 |
Secondary
Weekly Number of Puffs of As-needed SABA Use During the Primary Efficacy Assessment Period
Average weekly number of puffs of as-needed SABA use evaluates the treatment effect based on the reduction in the use of asthma reliever medication (SABA), and is calculated as 7 times the average of the daily number of puffs of as-needed SABA use. Higher values indicate more medication use.
Time frame: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP
Population: Participants with asthma in the full analysis set with observations in the primary efficacy period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HDM SLIT-tablet (12 SQ-HDM) | Weekly Number of Puffs of As-needed SABA Use During the Primary Efficacy Assessment Period | 1.0 weekly number of puffs | Standard Error 0.2 |
| Placebo SLIT-tablet | Weekly Number of Puffs of As-needed SABA Use During the Primary Efficacy Assessment Period | 1.5 weekly number of puffs | Standard Error 0.2 |
Comparison: The endpoint was analysed using a linear mixed effect (LME) model. The model includes the endpoint as response variable, treatment and cohort as fixed factors, the baseline value as a covariate, country/region within cohort as a random effect, and with different residual errors specified for each treatment. No missing data approach was applied.p-value: 0.125695% CI: [-0.1, 1]Mixed Models Analysis