Trial Outcomes & Findings for A Study in Children and Adolescents With Birch Pollen-induced Rhinoconjunctivitis (NCT NCT04878354)
NCT ID: NCT04878354
Last Updated: 2025-01-22
Results Overview
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.
COMPLETED
PHASE3
952 participants
During the BPS (mean duration of approximately 3-4 weeks)
2025-01-22
Participant Flow
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.
* 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)
Participant milestones
| Measure |
Placebo SLIT-tablet
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Overall Study
STARTED
|
479
|
473
|
|
Overall Study
Completed Trial
|
458
|
456
|
|
Overall Study
Full Analysis Set
|
479
|
473
|
|
Overall Study
Safety Analysis Set
|
479
|
473
|
|
Overall Study
Subgroup Analysis Set
|
132
|
119
|
|
Overall Study
COMPLETED
|
454
|
443
|
|
Overall Study
NOT COMPLETED
|
25
|
30
|
Reasons for withdrawal
| Measure |
Placebo SLIT-tablet
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
13
|
|
Overall Study
Withdrawal by Subject
|
14
|
12
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Reason stated as "other" in CRF
|
2
|
3
|
Baseline Characteristics
A Study in Children and Adolescents With Birch Pollen-induced Rhinoconjunctivitis
Baseline characteristics by cohort
| Measure |
Placebo SLIT-tablet
n=479 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
Total
n=952 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
479 Participants
n=5 Participants
|
473 Participants
n=7 Participants
|
952 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
10.2 years
STANDARD_DEVIATION 3.5 • n=5 Participants
|
10.4 years
STANDARD_DEVIATION 3.5 • n=7 Participants
|
10.3 years
STANDARD_DEVIATION 3.5 • n=5 Participants
|
|
Age, Customized
Age by group · 5-11 years
|
300 Participants
n=5 Participants
|
297 Participants
n=7 Participants
|
597 Participants
n=5 Participants
|
|
Age, Customized
Age by group · 12-17 years
|
179 Participants
n=5 Participants
|
176 Participants
n=7 Participants
|
355 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
194 Participants
n=5 Participants
|
185 Participants
n=7 Participants
|
379 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
285 Participants
n=5 Participants
|
288 Participants
n=7 Participants
|
573 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
471 Participants
n=5 Participants
|
463 Participants
n=7 Participants
|
934 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
473 Participants
n=5 Participants
|
468 Participants
n=7 Participants
|
941 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
42 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
24 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
225 Participants
n=5 Participants
|
221 Participants
n=7 Participants
|
446 Participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
40 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Region of Enrollment
Lithuania
|
46 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
92 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
44 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
39 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Allergic condition caused by birch
Allergic conjunctivitis
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Allergic condition caused by birch
Allergic rhinitis
|
122 participants
n=5 Participants
|
125 participants
n=7 Participants
|
247 participants
n=5 Participants
|
|
Allergic condition caused by birch
Allergic rhinoconjunctivitis
|
353 participants
n=5 Participants
|
346 participants
n=7 Participants
|
699 participants
n=5 Participants
|
|
Allergic condition caused by birch
Asthma
|
125 participants
n=5 Participants
|
126 participants
n=7 Participants
|
251 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Total Combined Score (TCS) During the Birch Pollen Season (BPS)
|
5.88 score on a scale
Standard Error 0.33
|
4.60 score on a scale
Standard Error 0.29
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Total Combined Score (TCS) During the Tree Pollen Season (TPS)
|
4.51 score on a scale
Standard Error 0.25
|
3.66 score on a scale
Standard Error 0.22
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Symptoms Score (DSS) During the Birch Pollen Season (BPS)
|
2.75 score on a scale
Standard Error 0.16
|
2.39 score on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks).Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Symptoms Score (DSS) During the Tree Pollen Season (TPS)
|
2.28 score on a scale
Standard Error 0.14
|
2.04 score on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Medication Score (DMS) During the Birch Pollen Season (BPS)
|
2.42 score on a scale
Standard Error 0.23
|
1.55 score on a scale
Standard Error 0.18
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Medication Score (DMS) During the Tree Pollen Season (TPS)
|
1.72 score on a scale
Standard Error 0.16
|
1.18 score on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: During the AHPS (mean duration of approximately 6-7 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=442 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=426 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Total Combined Score (TCS) During the Alder Hazel Pollen Season (AHPS)
|
2.83 score on a scale
Standard Error 0.22
|
2.51 score on a scale
Standard Error 0.21
|
SECONDARY outcome
Timeframe: During the AHPS (mean duration of approximately 6-7 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=442 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=426 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Symptoms Score (DSS) During the Alder Hazel Pollen Season (AHPS)
|
1.57 score on a scale
Standard Error 0.12
|
1.56 score on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: During the AHPS (mean duration of approximately 6-7 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=442 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=426 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Medication Score (DMS) During the Alder Hazel Pollen Season (AHPS)
|
0.80 score on a scale
Standard Error 0.11
|
0.59 score on a scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: During the OPS (mean duration of approximately 3 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=442 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=432 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Total Combined Score (TCS) During the Oak Pollen Season (OPS)
|
5.67 score on a scale
Standard Error 0.36
|
4.22 score on a scale
Standard Error 0.31
|
SECONDARY outcome
Timeframe: During the OPS (mean duration of approximately 3 weeks)Population: Participants in the full analysis set with observations.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=442 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=432 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Symptoms Score (DSS) During the Oak Pollen Season (OPS)
|
2.68 score on a scale
Standard Error 0.16
|
2.20 score on a scale
Standard Error 0.15
|
SECONDARY outcome
Timeframe: During the OPS (mean duration of approximately 3 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=442 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=432 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Daily Medication Score (DMS) During the Oak Pollen Season (OPS)
|
2.18 score on a scale
Standard Error 0.23
|
1.31 score on a scale
Standard Error 0.18
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Number of Severe Days During the Birch Pollen Season (BPS)
|
0.23 Proportion of severe days
|
0.20 Proportion of severe days
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Number of Severe Days During the Tree Pollen Season (TPS)
|
0.11 Proportion of severe days
|
0.11 Proportion of severe days
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Number of Well Days During the Birch Pollen Season (BPS)
|
0.36 Proportion of well days
|
0.43 Proportion of well days
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Number of Well Days During the Tree Pollen Season (TPS)
|
0.50 Proportion of well days
|
0.53 Proportion of well days
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Number of Symptom-free Days During the Birch Pollen Season (BPS)
|
0.24 Proportion of symptom-free days
|
0.29 Proportion of symptom-free days
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Number of Symptom-free Days During the Tree Pollen Season (TPS)
|
0.28 Proportion of symptom-free days
|
0.30 Proportion of symptom-free days
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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
Outcome measures
| Measure |
Placebo SLIT-tablet
n=479 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Birch Pollen Season (BPS)
No season data
|
19 Participants
|
18 Participants
|
|
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
|
20 Participants
|
|
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
|
435 Participants
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=479 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Percentage of Patients Free of Symptoms and With no Use of Rescue Medication During the Tree Pollen Season (TPS)
No season data
|
15 Participants
|
16 Participants
|
|
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
|
4 Participants
|
|
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
|
453 Participants
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=457 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=444 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Total Combined Score (TCS) (EAACI Scoring) During Birch Pollen Season (BPS)
|
0.95 score on a scale
Standard Error 0.05
|
0.77 score on a scale
Standard Error 0.05
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks).Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=461 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=448 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Average Total Combined Score (TCS) (EAACI Scoring) During Tree Pollen Season (TPS)
|
0.74 score on a scale
Standard Error 0.04
|
0.62 score on a scale
Standard Error 0.04
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=167 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=161 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
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
|
0.97 score on a scale
Standard Error 0.09
|
SECONDARY outcome
Timeframe: During the TPS (mean duration of approximately 11 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=172 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=166 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
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
|
0.86 score on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: During the BPS (mean duration of approximately 3-4 weeks)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=260 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=257 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
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
|
1.12 score on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=479 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Treatment Satisfaction (TSQM-9)
Convenience
|
79.6 score on a scale
Standard Deviation 14.7
|
78.2 score on a scale
Standard Deviation 15.3
|
|
Treatment Satisfaction (TSQM-9)
Effectiveness
|
59.8 score on a scale
Standard Deviation 21.1
|
67.6 score on a scale
Standard Deviation 18.4
|
|
Treatment Satisfaction (TSQM-9)
Global satisfaction
|
62.1 score on a scale
Standard Deviation 23.5
|
69.9 score on a scale
Standard Deviation 20.0
|
SECONDARY outcome
Timeframe: End of treatment (after approximately 52 weeks of treatment)Population: Participants in the full analysis set with observations
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=455 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=443 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Patient-rated Global Evaluation of Treatment Efficacy
|
0.70 Proportion
Interval 0.65 to 0.74
|
0.85 Proportion
Interval 0.81 to 0.88
|
SECONDARY outcome
Timeframe: 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.
Birch specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation
Outcome measures
| Measure |
Placebo SLIT-tablet
n=479 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Change From Baseline in Birch Specific IgE
Birch specific IgE, visit 4
|
-0.21 Log10 transformed kU/L
Interval -0.24 to -0.18
|
0.22 Log10 transformed kU/L
Interval 0.18 to 0.26
|
|
Change From Baseline in Birch Specific IgE
Birch specific IgE, visit 6
|
0.10 Log10 transformed kU/L
Interval 0.07 to 0.13
|
0.06 Log10 transformed kU/L
Interval 0.02 to 0.1
|
SECONDARY outcome
Timeframe: 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.
Birch specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=479 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Change From Baseline in Birch Specific IgG4
Birch specific IgG4, visit 4
|
-0.09 Log10 transformed mg/L
Interval -0.11 to -0.07
|
0.43 Log10 transformed mg/L
Interval 0.39 to 0.47
|
|
Change From Baseline in Birch Specific IgG4
Birch specific IgG4, visit 6
|
0.05 Log10 transformed mg/L
Interval 0.03 to 0.07
|
0.54 Log10 transformed mg/L
Interval 0.51 to 0.58
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=132 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=119 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF)
Birch specific IgE-BF, visit 4
|
-0.01 Unitless
Interval -0.03 to 0.01
|
0.28 Unitless
Interval 0.23 to 0.32
|
|
Change From Baseline in Birch Specific IgE-Blocking Factor (IgE-BF)
Birch specific IgE-BF, visit 6
|
0.04 Unitless
Interval 0.02 to 0.05
|
0.35 Unitless
Interval 0.3 to 0.4
|
SECONDARY outcome
Timeframe: 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.
Change in alder, hazel and oak specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=132 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=119 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Change From Baseline in Alder, Hazel and Oak Specific IgE
Alder specific IgE, visit 4
|
-0.22 log10 transformed kU/L
Standard Deviation 0.20
|
0.17 log10 transformed kU/L
Standard Deviation 0.41
|
|
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
|
0.10 log10 transformed kU/L
Standard Deviation 0.31
|
|
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
|
0.15 log10 transformed kU/L
Standard Deviation 0.38
|
|
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
|
0.11 log10 transformed kU/L
Standard Deviation 0.30
|
|
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
|
0.14 log10 transformed kU/L
Standard Deviation 0.37
|
|
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
|
0.11 log10 transformed kU/L
Standard Deviation 0.29
|
SECONDARY outcome
Timeframe: 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.
Change in alder, hazel and oak specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=132 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=119 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
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
|
0.32 log10 transformed mg/L
Standard Deviation 0.35
|
|
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
|
0.38 log10 transformed mg/L
Standard Deviation 0.39
|
|
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
|
0.51 log10 transformed mg/L
Standard Deviation 0.41
|
|
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
|
0.35 log10 transformed mg/L
Standard Deviation 0.39
|
|
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
|
0.46 log10 transformed mg/L
Standard Deviation 0.42
|
|
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
|
0.28 log10 transformed mg/L
Standard Deviation 0.39
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo SLIT-tablet
n=132 Participants
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=119 Participants
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
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
|
0.20 Unitless
Standard Deviation 0.18
|
|
Change From Baseline in Alder and Hazel Specific IgE- Blocking Factor (IgE-BF)
Hazel specific IgE-BF, visit 6
|
0.02 Unitless
Standard Deviation 0.10
|
0.14 Unitless
Standard Deviation 0.17
|
|
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
|
0.21 Unitless
Standard Deviation 0.19
|
|
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
|
0.15 Unitless
Standard Deviation 0.18
|
Adverse Events
Placebo SLIT-tablet
Tree SLIT-tablet
Serious adverse events
| Measure |
Placebo SLIT-tablet
n=479 participants at risk
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 participants at risk
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/479 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.21%
1/473 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Impetigo
|
0.00%
0/479 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.21%
1/473 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Infectious mononucleosis
|
0.00%
0/479 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.21%
1/473 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Appendicitis
|
0.21%
1/479 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.00%
0/473 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Lymph node abscess
|
0.21%
1/479 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.00%
0/473 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Peritonsillar abscess
|
0.21%
1/479 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.00%
0/473 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Tonsillitis
|
0.21%
1/479 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.00%
0/473 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/479 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.21%
1/473 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Surgical and medical procedures
Foot operation
|
0.00%
0/479 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.21%
1/473 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.21%
1/479 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.00%
0/473 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Injury, poisoning and procedural complications
Craniocerebral injury
|
0.21%
1/479 • Number of events 1 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
0.00%
0/473 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
Other adverse events
| Measure |
Placebo SLIT-tablet
n=479 participants at risk
Participants received 1 placebo sublingual immunotherapy (SLIT)-tablet daily plus rhinoconjunctivitis rescue medication as needed.
|
Tree SLIT-tablet
n=473 participants at risk
Participants received 1 tree sublingual immunotherapy (SLIT)-tablet, 12 SQ-Bet dose daily plus rhinoconjunctivitis rescue medication as needed.
|
|---|---|---|
|
Gastrointestinal disorders
Oral pruritus
|
3.5%
17/479 • Number of events 19 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
24.1%
114/473 • Number of events 136 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Gastrointestinal disorders
Tongue pruritus
|
1.3%
6/479 • Number of events 6 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
12.7%
60/473 • Number of events 76 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Gastrointestinal disorders
Paraesthesia oral
|
1.7%
8/479 • Number of events 8 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
5.9%
28/473 • Number of events 34 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Nasopharyngitis
|
17.1%
82/479 • Number of events 124 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
17.1%
81/473 • Number of events 109 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Upper respiratory tract infection
|
9.0%
43/479 • Number of events 55 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
8.9%
42/473 • Number of events 53 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Pharyngitis
|
4.4%
21/479 • Number of events 23 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
6.8%
32/473 • Number of events 35 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
COVID-19
|
9.0%
43/479 • Number of events 44 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
5.7%
27/473 • Number of events 28 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Infections and infestations
Influenza
|
5.2%
25/479 • Number of events 27 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
3.6%
17/473 • Number of events 18 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
3.8%
18/479 • Number of events 19 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
23.7%
112/473 • Number of events 140 • All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration (up to approximately 12 months).
All AEs with start date/time on or after the time of first IMP administration and no later than 7 days after last IMP administration are presented including "all-cause mortality"," serious adverse events" and "other (not including serious) adverse events". Both treatment-related and non-treatment-related AEs are displayed.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No publication can be made before the first multi-center publication. PI shall allow Sponsor (S) not less than 60 days to review publications and 30 days to review presentations. S can comment and require removal of confidential information. Upon S request, PI must delay the publication or presentation for 6 months to permit S to file a patent application or take other steps to protect S' information. Any other public statements regarding the trial requires prior written consent from S.
- Publication restrictions are in place
Restriction type: OTHER