Allergy
Conditions
Keywords
Allergic rhinoconjunctivitis, Children, Adolescents, Birch
Brief summary
This is a clinical study in children and adolescents (5-17 years) with allergy to pollen from birch (or related trees). It compares the tree SLIT-tablet with placebo in relieving rhinoconjunctivitis symptoms during the birch/tree pollen season based on the average allergic rhinoconjunctivitis daily total combined score. The study will also collect health-related quality of life information in the groups treated with the tree SLIT-tablet or with placebo during the pollen season. The trial medication used is already approved to treat allergic rhinitis caused by birch/tree pollen in adults in several countries?.
Detailed description
This is a phase III, parallel-group, double-blind, placebo-controlled study to evaluate efficacy and safety of the tree SLIT-tablet in children and adolescents (5-17 years) who have rhinoconjunctivitis (with or without asthma) induced by pollen from birch trees or by trees belonging to the birch homologous group. Approximately 1000 children and adolescents will be enrolled in the trial and will receive either the tree SLIT-tablet or placebo. The trial consists of 3 periods: a screening period, a treatment period, which includes pre-seasonal and co seasonal treatment, and a follow-up period. The duration is up to 13 months for each participant. The trial is conducted in several European countries and in Canada.
Interventions
DRUGPlacebo SLIT-tablet
Placebo
DRUGTree SLIT-tablet
Sublingual allergy immunotherapy tablets
Sponsors
Parexel
ALK-Abelló A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female of any race/ethnicity aged ≥4 to \<18 years on the day informed consent is obtained from the parent/caregiver; the subject must be ≥5 to \<18 years old at the randomisation visit * A documented , physician diagnosed, clinically relevant history of moderate to severe AR/C induced by birch pollen (with or without asthma) despite having received treatment with symptom-relieving medication during at least 1 previous tree pollen season for ages 4 through 6 years at screening or at least 2 previous tree pollen seasons for ages 7 through 17 years at screening * Positive skin prick test (SPT) to Betula verrucosa at screening * Positive specific IgE to Bet v at screening * Presence of 1 or more of the following Allergic Rhinitis Impact on Asthma (ARIA) quality of life items due to AR/C during the previous BPS: 1. Sleep disturbance 2. Impairment of daily activities, leisure and/or sport 3. Impairment of school or work 4. Troublesome symptoms
Exclusion criteria
* A clinically relevant history of symptomatic seasonal AR/C caused by an allergen source, other than tree pollen from the birch homologous group, with a season overlapping the TPS * A clinically relevant history of symptomatic perennial AR/C caused by an allergen source such as animal hair and dander to which the subject is exposed during the TPS * Any clinical deterioration of asthma (i.e. asthma exacerbation) that resulted in emergency treatment, hospitalisation or treatment with systemic corticosteroids within 3 months prior to randomisation * Reduced lung function at randomisation defined as forced expiratory volume in 1 second (FEV1) \<70% of predicted value. For subjects with asthma, this is assessed on subject's usual asthma medication following at least a 6-hour wash-out of SABA. This criterion does not need to be fulfilled if the subject is \<7 years old, cannot perform reproducible FEV1 manoeuvres despite coaching and is not considered as having a diagnosis of asthma * Ongoing treatment with any allergy immunotherapy product * Severe chronic oral inflammation * A diagnosis of eosinophilic oesophagitis * A relevant history of systemic allergic reaction e.g. anaphylaxis with cardiorespiratory symptoms, generalised urticaria or severe facial angioedema that in the opinion of the investigator may constitute an increased safety concern * Immunosuppressive treatment (ATC code L04 or L01) within 3 months prior to the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Total Combined Score (TCS) During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | The primary endpoint of the trial was the average allergic rhinitis and/or conjunctivitis TCS during the BPS. The average TCS evaluates the treatment effect based on 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 BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | Average rhinoconjunctivitis DSS during the BPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks). | Average rhinoconjunctivitis DSS during the TPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). TPS includes hazel, alder, birch and oak pollen seasons. Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | Average rhinoconjunctivitis DMS during the BPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks) | Average rhinoconjunctivitis DMS during the TPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). TPS includes hazel, alder, birch and oak pollen seasons. Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS) | During the AHPS (mean duration of approximately 6-7 weeks) | Average TCS during the AHPS evaluates the treatment effect based on 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 AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS) | During the AHPS (mean duration of approximately 6-7 weeks) | Average rhinoconjunctivitis DSS during the AHPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS) | During the AHPS (mean duration of approximately 6-7 weeks) | Average rhinoconjunctivitis DMS during the AHPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Number of Symptom-free Days During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | A a symptom-free day was defined as a day with no symptoms and with no use of rescue medication (Total Combined Score = 0). The proportion of symptom-free days was the number of symptom-free divided by the number of days in the season. |
| Average Total Combined Score (TCS) During the Oak Pollen Season (OPS) | During the OPS (mean duration of approximately 3 weeks) | Average TCS measured in the OPS evaluates the treatment effect based on 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 OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS) | During the OPS (mean duration of approximately 3 weeks) | Average rhinoconjunctivitis DSS during the OPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS) | During the OPS (mean duration of approximately 3 weeks) | Average rhinoconjunctivitis DMS during the OPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Number of Severe Days During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | The disease burden for participants was analyzed in terms of proportion of severe days. A severe day was a day with a daily symptom score (DSS) ≥6 and ≥2 moderate symptoms or 1 severe symptom. The DSS ranged from 0 to 18 and was the sum of the 6 allergic rhinoconjunctivitis symptom scores, each scored on a scale from 0 to 3 (0 = no symptoms, 1= mild symptoms, 2= moderate symptoms and 3 = severe symptoms). The proportion of severe days was the number of severe days divided by the number of days in the season. |
| Number of Severe Days During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks) | The disease burden for participants was analyzed in terms of proportion of severe days. A severe day was a day with a daily symptom score (DSS) ≥6 and ≥2 moderate symptoms or 1 severe symptom. The DSS ranged from 0 to 18 and was the sum of the 6 allergic rhinoconjunctivitis symptom scores, each scored on a scale from 0 to 3 (0 = no symptoms, 1= mild symptoms, 2= moderate symptoms and 3 = severe symptoms). The proportion of severe days was the number of severe days divided by the number of days in the season. |
| Number of Well Days During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | A well day was defined as a day with no use of allergic rhinitis and/or conjunctivitis (AR/C) rescue medication (daily medication score =0) and daily symptom score ≤2. The proportion of well days was the number of well days divided by the number of days in the season. |
| Number of Well Days During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks) | A well day was defined as a day with no use of allergic rhinitis and/or conjunctivitis (AR/C) rescue medication (daily medication score =0) and daily symptom score ≤2. The proportion of well days was the number of well days divided by the number of days in the season. |
| Average Total Combined Score (TCS) During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks) | Average TCS measured in the TPS. TPS includes hazel, alder, birch and oak pollen seasons. The average TCS evaluates the treatment effect based on 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 TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | A symptom-free day was defined as a day with no symptoms and with no use of rescue medication, i.e. total combined score (TCS) =0. Thus, the endpoint was categorized as a binary variable with a subject being a responder if he/she had no symptoms and had not used rescue medication during the season |
| Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks) | A symptom-free day was defined as a day with no symptoms and with no use of rescue medication, i.e. total combined score (TCS) = 0. Thus, the endpoint was categorized as a binary variable with a subject being a responder if he/she had no symptoms and had not used rescue medication during the tree pollen season. |
| Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS) | During the BPS (mean duration of approximately 3-4 weeks) | The TCS European Academy of Allergy and Clinical Immunology (EAACI) scoring was calculated using the medication score proposed by EAACI and was the sum of the DSS/6 and the daily EAACI medication score (DMSEAACI) (values 0,1,2), and thus ranged 0-5 with higher scores indicating more combined allergy symptoms and medication use. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks). | The TCS European Academy of Allergy and Clinical Immunology (EAACI) scoring was calculated using the medication score proposed by EAACI and was the sum of the DSS/6 and the daily EAACI medication score (DMSEAACI) (values 0,1,2), and thus ranged 0-5 with higher scores indicating more combined allergy symptoms and medication use. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only) | During the BPS (mean duration of approximately 3-4 weeks) | The RQLQ measured the rhinoconjunctivitis quality of life. The RQLQ (for participants 12-17 years only) comprised 28 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall RQLQ score was the mean of the 28 item scores. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only) | During the TPS (mean duration of approximately 11 weeks) | The RQLQ measured the rhinoconjunctivitis quality of life. The RQLQ (for participants 12-17 years only) comprised 28 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall RQLQ score was the mean of the 28 item scores. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only) | During the BPS (mean duration of approximately 3-4 weeks) | The PRQLQ measured the paediatric rhinoconjunctivitis quality of life. The PRQLQ consisted of 23 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall PRQLQ score was the mean of the 23 item scores. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Treatment Satisfaction (TSQM-9) | After ending treatment (after approximately 52 weeks of treatment) | Treatment satisfaction was measured using the 9-item treatment satisfaction questionnaire for medication (TSQM-9 questionnaire). After ending treatment, participants completed the TSQM-9 questionnaire which consisted of 9 items covering 3 domains. Each item was scored on a 5 point (ranging 1-5) or 7 point (ranging 1-7) scale. For each domain, item scores were summed and normalised to a 0-100 scale, with higher scores indicating better satisfaction. |
| Patient-rated Global Evaluation of Treatment Efficacy | End of treatment (after approximately 52 weeks of treatment) | The global evaluation measured patient treatment satisfaction. After ending treatment, participants were asked: 'Compared to your rhinitis and/or conjunctivitis symptoms in the previous birch/tree pollen season, how have you felt overall in this birch/tree pollen season?'. The endpoint was evaluated as a binary endpoint; answer options 'much better' and 'better' were categorised as improved (taking value 1), while answer options 'the same', 'worse', and 'much worse' were categorised as not improved (taking value 0). The primary estimand for the endpoint was he trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed. |
| Change From Baseline in Birch Specific IgE | From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average) | Birch specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation |
| Change From Baseline in Birch Specific IgG4 | From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average) | Birch specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation. |
| Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF) | From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average) | The IgE-blocking factor assesses the effect of serum components (including IgE-blocking 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. |
| Change From Baseline in Alder, Hazel and Oak Specific IgE | From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average) | Change in alder, hazel and oak specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation. |
| Change From Baseline in Alder, Hazel and Oak Specific IgG4 | From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average) | Change in alder, hazel and oak specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation. |
| Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks treatment, on average) | The IgE-blocking factor assesses the effect of serum components (including IgE-blocking 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. |
| Number of Symptom-free Days During the Tree Pollen Season (TPS) | During the TPS (mean duration of approximately 11 weeks) | A a symptom-free day was defined as a day with no symptoms and with no use of rescue medication (Total Combined Score = 0). The proportion of symptom-free days was the number of symptom-free divided by the number of days in the season. |
Countries
Austria, Belgium, Canada, Denmark, Germany, Hungary, Lithuania, Netherlands, Poland, Russia, Slovakia
Participant flow
Recruitment details
952 participants were randomized and treated. Participants were recruited from 80 sites in 11 countries (Austria, Belgium, Canada, Denmark, Germany, Hungary, Lithuania, Netherlands, Poland, Russia and Slovakia). First participant first visit: 08-Apr-2021. Last participant last visit/contact: 31-Jul-2023.
Pre-assignment details
* Male or female aged ≥5 to \<18 years at randomization * Documented, clinically relevant history of moderate to severe allergic rhinitis and/or conjunctivitis (AR/C) induced by birch pollen (with or without asthma) despite treatment with symptom-relieving medication * Positive skin prick test (SPT) and IgE against Betula verrucosa * Presence of at least 1 Allergic Rhinitis Impact on Asthma (ARIA) quality of life item due to AR/C during the previous birch pollen season (BPS)
Participants by arm
| Arm | Count |
|---|---|
| Placebo SLIT-tablet Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed. | 479 |
| Tree SLIT-tablet Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed. | 473 |
| Total | 952 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 13 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Reason stated as other in CRF | 2 | 3 |
| Overall Study | Withdrawal by Subject | 14 | 12 |
Baseline characteristics
| Characteristic | Placebo SLIT-tablet | Tree SLIT-tablet | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 479 Participants | 473 Participants | 952 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.2 years STANDARD_DEVIATION 3.5 | 10.4 years STANDARD_DEVIATION 3.5 | 10.3 years STANDARD_DEVIATION 3.5 |
| Age, Customized Age by group 12-17 years | 179 Participants | 176 Participants | 355 Participants |
| Age, Customized Age by group 5-11 years | 300 Participants | 297 Participants | 597 Participants |
| Allergic condition caused by birch Allergic conjunctivitis | 4 participants | 2 participants | 6 participants |
| Allergic condition caused by birch Allergic rhinitis | 122 participants | 125 participants | 247 participants |
| Allergic condition caused by birch Allergic rhinoconjunctivitis | 353 participants | 346 participants | 699 participants |
| Allergic condition caused by birch Asthma | 125 participants | 126 participants | 251 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 471 Participants | 463 Participants | 934 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 10 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 473 Participants | 468 Participants | 941 Participants |
| Region of Enrollment Austria | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment Belgium | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment Canada | 42 Participants | 45 Participants | 87 Participants |
| Region of Enrollment Denmark | 10 Participants | 8 Participants | 18 Participants |
| Region of Enrollment Germany | 44 Participants | 45 Participants | 89 Participants |
| Region of Enrollment Hungary | 24 Participants | 21 Participants | 45 Participants |
| Region of Enrollment Lithuania | 46 Participants | 46 Participants | 92 Participants |
| Region of Enrollment Netherlands | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Poland | 225 Participants | 221 Participants | 446 Participants |
| Region of Enrollment Russia | 39 Participants | 38 Participants | 77 Participants |
| Region of Enrollment Slovakia | 40 Participants | 39 Participants | 79 Participants |
| Sex: Female, Male Female | 194 Participants | 185 Participants | 379 Participants |
| Sex: Female, Male Male | 285 Participants | 288 Participants | 573 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 479 | 0 / 473 |
| other Total, other adverse events | 194 / 479 | 315 / 473 |
| serious Total, serious adverse events | 6 / 479 | 5 / 473 |
Outcome results
Primary
Average Total Combined Score (TCS) During the Birch Pollen Season (BPS)
The primary endpoint of the trial was the average allergic rhinitis and/or conjunctivitis TCS during the BPS. The average TCS evaluates the treatment effect based on 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 BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Total Combined Score (TCS) During the Birch Pollen Season (BPS) | 5.88 score on a scale | Standard Error 0.33 |
| Tree SLIT-tablet | Average Total Combined Score (TCS) During the Birch Pollen Season (BPS) | 4.60 score on a scale | Standard Error 0.29 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Adjusted p-value.p-value: 0.000495% CI: [0.58, 2]Mixed Models Analysis
Secondary
Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS)
Average rhinoconjunctivitis DMS during the AHPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the AHPS (mean duration of approximately 6-7 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS) | 0.80 score on a scale | Standard Error 0.11 |
| Tree SLIT-tablet | Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS) | 0.59 score on a scale | Standard Error 0.09 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.049995% CI: [0, 0.41]Mixed Models Analysis
Secondary
Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS)
Average rhinoconjunctivitis DMS during the BPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS) | 2.42 score on a scale | Standard Error 0.23 |
| Tree SLIT-tablet | Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS) | 1.55 score on a scale | Standard Error 0.18 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: <0.000195% CI: [0.45, 1.28]Mixed Models Analysis
Secondary
Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS)
Average rhinoconjunctivitis DMS during the OPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the OPS (mean duration of approximately 3 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS) | 2.18 score on a scale | Standard Error 0.23 |
| Tree SLIT-tablet | Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS) | 1.31 score on a scale | Standard Error 0.18 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: <0.000195% CI: [0.44, 1.29]Mixed Models Analysis
Secondary
Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS)
Average rhinoconjunctivitis DMS during the TPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0 to 20). TPS includes hazel, alder, birch and oak pollen seasons. Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS) | 1.72 score on a scale | Standard Error 0.16 |
| Tree SLIT-tablet | Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS) | 1.18 score on a scale | Standard Error 0.13 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.000295% CI: [0.26, 0.82]Mixed Models Analysis
Secondary
Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS)
Average rhinoconjunctivitis DSS during the AHPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the AHPS (mean duration of approximately 6-7 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS) | 1.57 score on a scale | Standard Error 0.12 |
| Tree SLIT-tablet | Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS) | 1.56 score on a scale | Standard Error 0.13 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.970995% CI: [-0.24, 0.25]Mixed Models Analysis
Secondary
Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS)
Average rhinoconjunctivitis DSS during the BPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the BPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS) | 2.75 score on a scale | Standard Error 0.16 |
| Tree SLIT-tablet | Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS) | 2.39 score on a scale | Standard Error 0.15 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Adjusted p-value.p-value: 0.035495% CI: [0.03, 0.71]Mixed Models Analysis
Secondary
Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS)
Average rhinoconjunctivitis DSS during the OPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the OPS (mean duration of approximately 3 weeks)
Population: Participants in the full analysis set with observations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS) | 2.68 score on a scale | Standard Error 0.16 |
| Tree SLIT-tablet | Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS) | 2.20 score on a scale | Standard Error 0.15 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.007595% CI: [0.13, 0.83]Mixed Models Analysis
Secondary
Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS)
Average rhinoconjunctivitis DSS during the TPS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms (on a scale of 0 to 18). TPS includes hazel, alder, birch and oak pollen seasons. Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the TPS (mean duration of approximately 11 weeks).
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS) | 2.28 score on a scale | Standard Error 0.14 |
| Tree SLIT-tablet | Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS) | 2.04 score on a scale | Standard Error 0.13 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Adjusted p-value.p-value: 0.073495% CI: [-0.02, 0.5]Mixed Models Analysis
Secondary
Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS)
Average TCS during the AHPS evaluates the treatment effect based on 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 AHPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the AHPS (mean duration of approximately 6-7 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS) | 2.83 score on a scale | Standard Error 0.22 |
| Tree SLIT-tablet | Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS) | 2.51 score on a scale | Standard Error 0.21 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.151695% CI: [-0.11, 0.76]Mixed Models Analysis
Secondary
Average Total Combined Score (TCS) During the Oak Pollen Season (OPS)
Average TCS measured in the OPS evaluates the treatment effect based on 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 OPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the OPS (mean duration of approximately 3 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Total Combined Score (TCS) During the Oak Pollen Season (OPS) | 5.67 score on a scale | Standard Error 0.36 |
| Tree SLIT-tablet | Average Total Combined Score (TCS) During the Oak Pollen Season (OPS) | 4.22 score on a scale | Standard Error 0.31 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: <0.000195% CI: [0.73, 2.18]Mixed Models Analysis
Secondary
Average Total Combined Score (TCS) During the Tree Pollen Season (TPS)
Average TCS measured in the TPS. TPS includes hazel, alder, birch and oak pollen seasons. The average TCS evaluates the treatment effect based on 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 TPS. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Total Combined Score (TCS) During the Tree Pollen Season (TPS) | 4.51 score on a scale | Standard Error 0.25 |
| Tree SLIT-tablet | Average Total Combined Score (TCS) During the Tree Pollen Season (TPS) | 3.66 score on a scale | Standard Error 0.22 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Adjusted p-value.p-value: 0.00195% CI: [0.34, 1.35]Mixed Models Analysis
Secondary
Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS)
The TCS European Academy of Allergy and Clinical Immunology (EAACI) scoring was calculated using the medication score proposed by EAACI and was the sum of the DSS/6 and the daily EAACI medication score (DMSEAACI) (values 0,1,2), and thus ranged 0-5 with higher scores indicating more combined allergy symptoms and medication use. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS) | 0.95 score on a scale | Standard Error 0.05 |
| Tree SLIT-tablet | Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS) | 0.77 score on a scale | Standard Error 0.05 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in an LME model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.001595% CI: [0.07, 0.29]Mixed Models Analysis
Secondary
Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS)
The TCS European Academy of Allergy and Clinical Immunology (EAACI) scoring was calculated using the medication score proposed by EAACI and was the sum of the DSS/6 and the daily EAACI medication score (DMSEAACI) (values 0,1,2), and thus ranged 0-5 with higher scores indicating more combined allergy symptoms and medication use. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the TPS (mean duration of approximately 11 weeks).
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS) | 0.74 score on a scale | Standard Error 0.04 |
| Tree SLIT-tablet | Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS) | 0.62 score on a scale | Standard Error 0.04 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The square root transformed endpoint was analysed in a linear mixed effects (LME) model with treatment, cohort, and age group as fixed effects, and pollen station within cohort as a random effect with different residual errors specified for each treatment group. Back-transformation was used to estimate the absolute difference. Observed p-value.p-value: 0.003295% CI: [0.04, 0.2]Mixed Models Analysis
Secondary
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only)
The RQLQ measured the rhinoconjunctivitis quality of life. The RQLQ (for participants 12-17 years only) comprised 28 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall RQLQ score was the mean of the 28 item scores. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only) | 0.98 score on a scale | Standard Error 0.09 |
| Tree SLIT-tablet | Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Birch Pollen Season (BPS) (12-17 Years Only) | 0.97 score on a scale | Standard Error 0.09 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The endpoint was analysed in each dataset in a linear mixed effects (LME) model with treatment and cohort as fixed effects, and pollen station within cohort as a random effect. Each treatment group was allowed different residual errors. Observed p-value.p-value: 0.927795% CI: [-0.21, 0.23]Mixed Models Analysis
Secondary
Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only)
The RQLQ measured the rhinoconjunctivitis quality of life. The RQLQ (for participants 12-17 years only) comprised 28 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall RQLQ score was the mean of the 28 item scores. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only) | 0.85 score on a scale | Standard Error 0.07 |
| Tree SLIT-tablet | Average Weekly Overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Score During the Tree Pollen Season (TPS) (12-17 Years Only) | 0.86 score on a scale | Standard Error 0.08 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The endpoint was analysed in each dataset in a linear mixed effect (LME) model with treatment and cohort as fixed effects, and pollen station within cohort as a random effect. Each treatment group was allowed different residual errors. Observed p-value.p-value: 0.964395% CI: [-0.19, 0.18]Mixed Models Analysis
Secondary
Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF)
The IgE-blocking factor assesses the effect of serum components (including IgE-blocking 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: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks treatment, on average)
Population: Alder and hazel specific IgE-BF levels were measured in 132 placebo and 119 tree SLIT-tablet participants. Data were not provided by all participants for both visit 4 and visit 6, thus the overall number of participants analyzed differs from the number analyzed at the specified visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Alder specific IgE-BF, visit 4 | -0.03 Unitless | Standard Deviation 0.08 |
| Placebo SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Alder specific IgE-BF, visit 6 | 0.04 Unitless | Standard Deviation 0.13 |
| Placebo SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Hazel specific IgE-BF, visit 4 | -0.03 Unitless | Standard Deviation 0.08 |
| Placebo SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Hazel specific IgE-BF, visit 6 | 0.02 Unitless | Standard Deviation 0.1 |
| Tree SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Hazel specific IgE-BF, visit 6 | 0.14 Unitless | Standard Deviation 0.17 |
| Tree SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Alder specific IgE-BF, visit 4 | 0.20 Unitless | Standard Deviation 0.18 |
| Tree SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Hazel specific IgE-BF, visit 4 | 0.15 Unitless | Standard Deviation 0.18 |
| Tree SLIT-tablet | Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF) | Alder specific IgE-BF, visit 6 | 0.21 Unitless | Standard Deviation 0.19 |
Secondary
Change From Baseline in Alder, Hazel and Oak Specific IgE
Change in alder, hazel and oak specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Population: Alder, hazel and oak specific IgE levels were measured in 132 placebo and 119 tree SLIT-tablet participants. Data were not provided by all participants for both visit 4 and visit 6, thus the overall number of participants analyzed differs from the number analyzed at the specified visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Alder specific IgE, visit 4 | -0.22 log10 transformed kU/L | Standard Deviation 0.2 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Alder specific IgE, visit 6 | 0.18 log10 transformed kU/L | Standard Deviation 0.34 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Hazel specific IgE, visit 4 | -0.22 log10 transformed kU/L | Standard Deviation 0.21 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Hazel specific IgE, visit 6 | 0.20 log10 transformed kU/L | Standard Deviation 0.36 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Oak specific IgE, visit 4 | -0.21 log10 transformed kU/L | Standard Deviation 0.17 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Oak specific IgE, visit 6 | 0.20 log10 transformed kU/L | Standard Deviation 0.34 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Oak specific IgE, visit 4 | 0.14 log10 transformed kU/L | Standard Deviation 0.37 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Alder specific IgE, visit 4 | 0.17 log10 transformed kU/L | Standard Deviation 0.41 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Hazel specific IgE, visit 6 | 0.11 log10 transformed kU/L | Standard Deviation 0.3 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Alder specific IgE, visit 6 | 0.10 log10 transformed kU/L | Standard Deviation 0.31 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Oak specific IgE, visit 6 | 0.11 log10 transformed kU/L | Standard Deviation 0.29 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgE | Hazel specific IgE, visit 4 | 0.15 log10 transformed kU/L | Standard Deviation 0.38 |
Secondary
Change From Baseline in Alder, Hazel and Oak Specific IgG4
Change in alder, hazel and oak specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Population: Alder, hazel and oak specific IgG4 levels were measured in 132 placebo and 119 tree SLIT-tablet participants. Data were not provided by all participants for both visit 4 and visit 6, thus the overall number of participants analyzed differs from the number analyzed at the specified visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Hazel specific IgG4, visit 4 | -0.08 log10 transformed mg/L | Standard Deviation 0.19 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Alder specific IgG4, visit 4 | -0.08 log10 transformed mg/L | Standard Deviation 0.18 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Alder specific IgG4, visit 6 | 0.13 log10 transformed mg/L | Standard Deviation 0.26 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Hazel specific IgG4, visit 6 | 0.11 log10 transformed mg/L | Standard Deviation 0.24 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Oak specific IgG4, visit 4 | -0.07 log10 transformed mg/L | Standard Deviation 0.14 |
| Placebo SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Oak specific IgG4, visit 6 | 0.08 log10 transformed mg/L | Standard Deviation 0.21 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Oak specific IgG4, visit 4 | 0.28 log10 transformed mg/L | Standard Deviation 0.39 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Hazel specific IgG4, visit 4 | 0.35 log10 transformed mg/L | Standard Deviation 0.39 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Hazel specific IgG4, visit 6 | 0.46 log10 transformed mg/L | Standard Deviation 0.42 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Alder specific IgG4, visit 4 | 0.38 log10 transformed mg/L | Standard Deviation 0.39 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Oak specific IgG4, visit 6 | 0.32 log10 transformed mg/L | Standard Deviation 0.35 |
| Tree SLIT-tablet | Change From Baseline in Alder, Hazel and Oak Specific IgG4 | Alder specific IgG4, visit 6 | 0.51 log10 transformed mg/L | Standard Deviation 0.41 |
Secondary
Change From Baseline in Birch Specific IgE
Birch specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Population: Birch specific IgE levels were measured in 479 placebo and 473 tree SLIT-tablet participants. Data were not provided by all participants for both visit 4 and visit 6, thus the overall number of participants analyzed differs from the number analyzed at the specified visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo SLIT-tablet | Change From Baseline in Birch Specific IgE | Birch specific IgE, visit 4 | -0.21 Log10 transformed kU/L |
| Placebo SLIT-tablet | Change From Baseline in Birch Specific IgE | Birch specific IgE, visit 6 | 0.10 Log10 transformed kU/L |
| Tree SLIT-tablet | Change From Baseline in Birch Specific IgE | Birch specific IgE, visit 4 | 0.22 Log10 transformed kU/L |
| Tree SLIT-tablet | Change From Baseline in Birch Specific IgE | Birch specific IgE, visit 6 | 0.06 Log10 transformed kU/L |
Comparison: Change from baseline (screening) to visit 4 (pre-TPS). Change from baseline of log transformed concentrations is analyzed in a mixed effects linear model including treatment, visit, and treatment-visit-interaction as fixed effects, log(baseline concentration) as a covariate and subject as random effect. Observed p-value.p-value: <0.000195% CI: [0.38, 0.48]Mixed Models Analysis
Comparison: Change from baseline (screening) to visit 6 (end of treatment). Change from baseline of log transformed concentrations is analysed in a mixed effects linear model including treatment, visit, and treatment-visit-interaction as fixed effects, log(baseline concentration) as a covariate and subject as random effect. Observed p-value.p-value: 0.103895% CI: [-0.09, 0.01]Mixed Models Analysis
Secondary
Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF)
The IgE-blocking factor assesses the effect of serum components (including IgE-blocking 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: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Population: Birch specific IgE-BF levels were measured in 132 placebo and 119 tree SLIT-tablet participants. Data were not provided by all participants for both visit 4 and visit 6, thus the overall number of participants analyzed differs from the number analyzed at the specified visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo SLIT-tablet | Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF) | Birch specific IgE-BF, visit 4 | -0.01 Unitless |
| Placebo SLIT-tablet | Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF) | Birch specific IgE-BF, visit 6 | 0.04 Unitless |
| Tree SLIT-tablet | Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF) | Birch specific IgE-BF, visit 4 | 0.28 Unitless |
| Tree SLIT-tablet | Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF) | Birch specific IgE-BF, visit 6 | 0.35 Unitless |
Comparison: Change from baseline (screening) to visit 4 (pre-TPS). Change from baseline of log transformed concentrations is analyzed in a mixed effects linear model including treatment, visit, and treatment-visit-interaction as fixed effects, log(baseline concentration) as a covariate and subject as random effect. Observed p-value.p-value: <0.000195% CI: [0.24, 0.33]Mixed Models Analysis
Comparison: Change from baseline (screening) to visit 6 (end of treatment). Change from baseline of log transformed concentrations is analysed in a mixed effects linear model including treatment, visit, and treatment-visit-interaction as fixed effects, log(baseline concentration) as a covariate and subject as random effect. Observed p-value.p-value: <0.000195% CI: [0.26, 0.36]Mixed Models Analysis
Secondary
Change From Baseline in Birch Specific IgG4
Birch specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Time frame: From baseline (screening) to visit 4 (pre-TPS) (after approximately 19 weeks of treatment, on average) and from baseline (screening) to visit 6 (end of treatment) (after approximately 44 weeks of treatment, on average)
Population: Birch specific IgG4 levels were measured in 479 placebo and 473 tree SLIT-tablet participants. Data were not provided by all participants for both visit 4 and visit 6, thus the overall number of participants analyzed differs from the number analyzed at the specified visits.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo SLIT-tablet | Change From Baseline in Birch Specific IgG4 | Birch specific IgG4, visit 4 | -0.09 Log10 transformed mg/L |
| Placebo SLIT-tablet | Change From Baseline in Birch Specific IgG4 | Birch specific IgG4, visit 6 | 0.05 Log10 transformed mg/L |
| Tree SLIT-tablet | Change From Baseline in Birch Specific IgG4 | Birch specific IgG4, visit 4 | 0.43 Log10 transformed mg/L |
| Tree SLIT-tablet | Change From Baseline in Birch Specific IgG4 | Birch specific IgG4, visit 6 | 0.54 Log10 transformed mg/L |
Comparison: Change from baseline (screening) to visit 4 (pre-TPS). Change from baseline of log transformed concentrations is analysed in a mixed effects linear model including treatment, visit, and treatment-visit-interaction as fixed effects, log(baseline concentration) as a covariate and subject as random effect. Observed p-value.p-value: <0.000195% CI: [0.48, 0.57]Mixed Models Analysis
Comparison: Change from baseline (screening) to visit 6 (end of treatment). Change from baseline of log transformed concentrations is analysed in a mixed effects linear model including treatment, visit, and treatment-visit-interaction as fixed effects, log(baseline concentration) as a covariate and subject as random effect. Observed p-value.p-value: <0.000195% CI: [0.45, 0.53]Mixed Models Analysis
Secondary
Number of Severe Days During the Birch Pollen Season (BPS)
The disease burden for participants was analyzed in terms of proportion of severe days. A severe day was a day with a daily symptom score (DSS) ≥6 and ≥2 moderate symptoms or 1 severe symptom. The DSS ranged from 0 to 18 and was the sum of the 6 allergic rhinoconjunctivitis symptom scores, each scored on a scale from 0 to 3 (0 = no symptoms, 1= mild symptoms, 2= moderate symptoms and 3 = severe symptoms). The proportion of severe days was the number of severe days divided by the number of days in the season.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Number of Severe Days During the Birch Pollen Season (BPS) | 0.23 Proportion of severe days |
| Tree SLIT-tablet | Number of Severe Days During the Birch Pollen Season (BPS) | 0.20 Proportion of severe days |
Comparison: The odds of having a severe day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model includes proportion of severe days as the response variable and treatment, cohort, and age group as fixed effects and pollen station as random effect. Observed p-value.p-value: <0.000195% CI: [1.1, 1.32]Generalised linear mixed model (GLMM)
Secondary
Number of Severe Days During the Tree Pollen Season (TPS)
The disease burden for participants was analyzed in terms of proportion of severe days. A severe day was a day with a daily symptom score (DSS) ≥6 and ≥2 moderate symptoms or 1 severe symptom. The DSS ranged from 0 to 18 and was the sum of the 6 allergic rhinoconjunctivitis symptom scores, each scored on a scale from 0 to 3 (0 = no symptoms, 1= mild symptoms, 2= moderate symptoms and 3 = severe symptoms). The proportion of severe days was the number of severe days divided by the number of days in the season.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Number of Severe Days During the Tree Pollen Season (TPS) | 0.11 Proportion of severe days |
| Tree SLIT-tablet | Number of Severe Days During the Tree Pollen Season (TPS) | 0.11 Proportion of severe days |
Comparison: The odds of having a severe day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model includes proportion of severe days as the response variable and treatment, cohort, and age group as fixed effects and pollen station as random effect. Observed p-value.p-value: 0.912495% CI: [0.93, 1.08]Generalised linear mixed model (GLMM)
Secondary
Number of Symptom-free Days During the Birch Pollen Season (BPS)
A a symptom-free day was defined as a day with no symptoms and with no use of rescue medication (Total Combined Score = 0). The proportion of symptom-free days was the number of symptom-free divided by the number of days in the season.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Number of Symptom-free Days During the Birch Pollen Season (BPS) | 0.24 Proportion of symptom-free days |
| Tree SLIT-tablet | Number of Symptom-free Days During the Birch Pollen Season (BPS) | 0.29 Proportion of symptom-free days |
Comparison: The odds of having a symptom-free day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model includes proportion of symptom-free days as the response variable and treatment, cohort, and age group as fixed effects and pollen station as random effect. Observed p-value.p-value: <0.000195% CI: [0.72, 0.84]Generalised linear mixed model (GLMM)
Secondary
Number of Symptom-free Days During the Tree Pollen Season (TPS)
A a symptom-free day was defined as a day with no symptoms and with no use of rescue medication (Total Combined Score = 0). The proportion of symptom-free days was the number of symptom-free divided by the number of days in the season.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Number of Symptom-free Days During the Tree Pollen Season (TPS) | 0.28 Proportion of symptom-free days |
| Tree SLIT-tablet | Number of Symptom-free Days During the Tree Pollen Season (TPS) | 0.30 Proportion of symptom-free days |
Comparison: The odds of having a symptom-free day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model includes proportion of symptom-free days as the response variable and treatment, cohort, and age group as fixed effects and pollen station as random effect. Observed p-value.p-value: 0.000195% CI: [0.86, 0.95]Generalised linear mixed model (GLMM)
Secondary
Number of Well Days During the Birch Pollen Season (BPS)
A well day was defined as a day with no use of allergic rhinitis and/or conjunctivitis (AR/C) rescue medication (daily medication score =0) and daily symptom score ≤2. The proportion of well days was the number of well days divided by the number of days in the season.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Number of Well Days During the Birch Pollen Season (BPS) | 0.36 Proportion of well days |
| Tree SLIT-tablet | Number of Well Days During the Birch Pollen Season (BPS) | 0.43 Proportion of well days |
Comparison: The odds of having a well day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model includes proportion of well days as the response variable and treatment, cohort, and age group as fixed effects and pollen station as random effect. Observed p-value.p-value: <0.000195% CI: [0.71, 0.81]Generalised linear fixed model (GLMM)
Secondary
Number of Well Days During the Tree Pollen Season (TPS)
A well day was defined as a day with no use of allergic rhinitis and/or conjunctivitis (AR/C) rescue medication (daily medication score =0) and daily symptom score ≤2. The proportion of well days was the number of well days divided by the number of days in the season.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Number of Well Days During the Tree Pollen Season (TPS) | 0.50 Proportion of well days |
| Tree SLIT-tablet | Number of Well Days During the Tree Pollen Season (TPS) | 0.53 Proportion of well days |
Comparison: The odds of having a well day was analysed using a generalised linear mixed model (GLMM) with a logit link function. The model includes proportion of well days as the response variable and treatment, cohort, and age group as fixed effects and pollen station as random effect. Observed p-value.p-value: <0.000195% CI: [0.85, 0.93]Generalised linear mixed model (GLMM)
Secondary
Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only)
The PRQLQ measured the paediatric rhinoconjunctivitis quality of life. The PRQLQ consisted of 23 items, each scored on a 7-point scale ranging 0-6, with higher scores indicating worse quality of life. The overall PRQLQ score was the mean of the 23 item scores. The primary estimand for the endpoint was the trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo SLIT-tablet | Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only) | 1.30 score on a scale | Standard Error 0.07 |
| Tree SLIT-tablet | Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score During the Birch Pollen Season (BPS) (5-11 Years Only) | 1.12 score on a scale | Standard Error 0.07 |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy. The endpoint was analysed in each dataset in a linear mixed effect (LME) model with treatment and cohort as fixed effects, and pollen station within cohort as a random effect. Each treatment group was allowed different residual errors. Observed p-value.p-value: 0.028795% CI: [0.02, 0.34]Mixed Models Analysis
Secondary
Patient-rated Global Evaluation of Treatment Efficacy
The global evaluation measured patient treatment satisfaction. After ending treatment, participants were asked: 'Compared to your rhinitis and/or conjunctivitis symptoms in the previous birch/tree pollen season, how have you felt overall in this birch/tree pollen season?'. The endpoint was evaluated as a binary endpoint; answer options 'much better' and 'better' were categorised as improved (taking value 1), while answer options 'the same', 'worse', and 'much worse' were categorised as not improved (taking value 0). The primary estimand for the endpoint was he trial product estimand. The trial product estimand assesses the anticipated effect of the tree SLIT-tablet if it is taken as instructed.
Time frame: End of treatment (after approximately 52 weeks of treatment)
Population: Participants in the full analysis set with observations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo SLIT-tablet | Patient-rated Global Evaluation of Treatment Efficacy | 0.70 Proportion |
| Tree SLIT-tablet | Patient-rated Global Evaluation of Treatment Efficacy | 0.85 Proportion |
Comparison: Multiple imputation was used to impute missing data under the hypothetical strategy.~The odds of having an improved treatment efficacy according to patient-rated global evaluation was analysed using a generalised linear mixed model with a logit link function. The model includes patient-rated global evaluation of treatment efficacy (improvement/no improvement) as the response variable and treatment, cohort and age group as fixed effects and pollen station as random effects. Observed p-value.p-value: <0.000195% CI: [0.3, 0.58]Generalized linear mixed model (GLMM)
Secondary
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS)
A symptom-free day was defined as a day with no symptoms and with no use of rescue medication, i.e. total combined score (TCS) =0. Thus, the endpoint was categorized as a binary variable with a subject being a responder if he/she had no symptoms and had not used rescue medication during the season
Time frame: During the BPS (mean duration of approximately 3-4 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | No season data | 19 Participants |
| Placebo SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | TCS=0 all days | 21 Participants |
| Placebo SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | TCS> 0 any day | 439 Participants |
| Tree SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | No season data | 18 Participants |
| Tree SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | TCS=0 all days | 20 Participants |
| Tree SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS) | TCS> 0 any day | 435 Participants |
Secondary
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS)
A symptom-free day was defined as a day with no symptoms and with no use of rescue medication, i.e. total combined score (TCS) = 0. Thus, the endpoint was categorized as a binary variable with a subject being a responder if he/she had no symptoms and had not used rescue medication during the tree pollen season.
Time frame: During the TPS (mean duration of approximately 11 weeks)
Population: Participants in the full analysis set with observations
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | No season data | 15 Participants |
| Placebo SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | TCS = 0 all days | 10 Participants |
| Placebo SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | TCS > 0 any day | 454 Participants |
| Tree SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | No season data | 16 Participants |
| Tree SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | TCS = 0 all days | 4 Participants |
| Tree SLIT-tablet | Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS) | TCS > 0 any day | 453 Participants |
Secondary
Treatment Satisfaction (TSQM-9)
Treatment satisfaction was measured using the 9-item treatment satisfaction questionnaire for medication (TSQM-9 questionnaire). After ending treatment, participants completed the TSQM-9 questionnaire which consisted of 9 items covering 3 domains. Each item was scored on a 5 point (ranging 1-5) or 7 point (ranging 1-7) scale. For each domain, item scores were summed and normalised to a 0-100 scale, with higher scores indicating better satisfaction.
Time frame: After ending treatment (after approximately 52 weeks of treatment)
Population: Patient-reported outcomes were collected from 479 placebo and 473 tree SLIT-tablet participants. Not all participants provided data for the 3 categories (convenience, effectiveness, and global satisfaction) resulting in different participant numbers analyzed in each category. The endpoint comprises the 3 categories, and thus to report the endpoint as one, the categories are reported together.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SLIT-tablet | Treatment Satisfaction (TSQM-9) | Effectiveness | 59.8 score on a scale | Standard Deviation 21.1 |
| Placebo SLIT-tablet | Treatment Satisfaction (TSQM-9) | Convenience | 79.6 score on a scale | Standard Deviation 14.7 |
| Placebo SLIT-tablet | Treatment Satisfaction (TSQM-9) | Global satisfaction | 62.1 score on a scale | Standard Deviation 23.5 |
| Tree SLIT-tablet | Treatment Satisfaction (TSQM-9) | Convenience | 78.2 score on a scale | Standard Deviation 15.3 |
| Tree SLIT-tablet | Treatment Satisfaction (TSQM-9) | Effectiveness | 67.6 score on a scale | Standard Deviation 18.4 |
| Tree SLIT-tablet | Treatment Satisfaction (TSQM-9) | Global satisfaction | 69.9 score on a scale | Standard Deviation 20 |