Trial Outcomes & Findings for House Dust Mite Allergy Trial In Children (NCT NCT04145219)

Last Updated: 2024-06-12

Results Overview

The primary endpoint in the trial was the average daily total combined rhinitis symptoms and medication score (TCRS) during the primary efficacy assessment period. The average daily TCRS evaluates the treatment effect based on the reduction in daily rhinitis symptoms and medication score (on a scale of 0-24). Higher scores indicate more severe symptoms and/or more use of rhinitis medication. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 daily TCRS values, the primary endpoint is calculated as the average of those values.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1460 participants

Primary outcome timeframe

8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Results posted on

2024-06-12

Participant Flow

The trial randomized 1460 participants from 95 sites in 11 countries (Bulgaria, Canada, France, Germany, Lithuania, Poland, Russia, Slovakia, Spain, Ukraine, United States).

The trial randomized 1460 participants. Two participants in the 12 SQ-HDM group were randomized in error and did not receive study treatment, hence the number of participants that started (who were randomized and treated) is 1458.

Participant milestones

Participant milestones
Measure	HDM SLIT-tablet (12 SQ-HDM) Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Overall Study STARTED	727	731
Overall Study COMPLETED	688	705
Overall Study NOT COMPLETED	39	26

Reasons for withdrawal

Reasons for withdrawal
Measure	HDM SLIT-tablet (12 SQ-HDM) Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Overall Study Adverse Event	18	6
Overall Study Lost to Follow-up	2	3
Overall Study Physician Decision	0	2
Overall Study Withdrawal by Subject	12	8
Overall Study Reason stated as 'Other' in the case report form (CRF)	7	7

Baseline Characteristics

House Dust Mite Allergy Trial In Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HDM SLIT-tablet (12 SQ-HDM) n=727 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=731 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).	Total n=1458 Participants Total of all reporting groups
Age, Continuous	8.0 years STANDARD_DEVIATION 1.9 • n=5 Participants	8.0 years STANDARD_DEVIATION 1.9 • n=7 Participants	8.0 years STANDARD_DEVIATION 1.9 • n=5 Participants
Sex: Female, Male Female	241 Participants n=5 Participants	254 Participants n=7 Participants	495 Participants n=5 Participants
Sex: Female, Male Male	486 Participants n=5 Participants	477 Participants n=7 Participants	963 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=5 Participants	19 Participants n=7 Participants	45 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	688 Participants n=5 Participants	697 Participants n=7 Participants	1385 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	722 Participants n=5 Participants	714 Participants n=7 Participants	1436 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Multiple	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Canada	18 participants n=5 Participants	20 participants n=7 Participants	38 participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	19 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Ukraine	165 participants n=5 Participants	165 participants n=7 Participants	330 participants n=5 Participants
Region of Enrollment Poland	176 participants n=5 Participants	177 participants n=7 Participants	353 participants n=5 Participants
Region of Enrollment Slovakia	33 participants n=5 Participants	33 participants n=7 Participants	66 participants n=5 Participants
Region of Enrollment Bulgaria	91 participants n=5 Participants	90 participants n=7 Participants	181 participants n=5 Participants
Region of Enrollment France	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Lithuania	47 participants n=5 Participants	47 participants n=7 Participants	94 participants n=5 Participants
Region of Enrollment Germany	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Russia	163 participants n=5 Participants	166 participants n=7 Participants	329 participants n=5 Participants
Region of Enrollment Spain	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Allergy history	726 Participants n=5 Participants	731 Participants n=7 Participants	1457 Participants n=5 Participants
Baseline sensitisations House dust mite only	337 Participants n=5 Participants	360 Participants n=7 Participants	697 Participants n=5 Participants
Baseline sensitisations House dust mite and others	390 Participants n=5 Participants	371 Participants n=7 Participants	761 Participants n=5 Participants
Asthma status at baseline Reported asthma	267 Participants n=5 Participants	290 Participants n=7 Participants	557 Participants n=5 Participants
Asthma status at baseline ICS use	148 Participants n=5 Participants	160 Participants n=7 Participants	308 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Average Daily Total Combined Rhinitis Symptom and Medication Score (TCRS) During the Primary Efficacy Assessment Period	3.4 score on a scale Standard Error 0.3	4.4 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period

The average rhinitis DSS evaluates the treatment effect based on the reduction in daily rhinitis symptom score (on a scale of 0-12). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis DSS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
The Average Rhinitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period	1.5 score on a scale Standard Error 0.1	1.9 score on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period.

Average rhinitis DMS evaluates the treatment effect based on the reduction in daily rhinitis medication use (on a scale of 0-12). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis DMS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
The Average Rhinitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period	1.4 score on a scale Standard Error 0.2	1.9 score on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period

Average rhinoconjunctivitis TCS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms and medication use (on a scale of 0-38). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 daily TCS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
The Average Daily Total Combined Rhinoconjunctivitis Symptom and Medication Score (TCS) During the Primary Efficacy Assessment Period	4.0 score on a scale Standard Error 0.4	5.2 score on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period

The average rhinoconjunctivitis DSS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptom score (on a scale of 0-18). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis DSS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
The Average Rhinoconjunctivitis Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period	1.7 score on a scale Standard Error 0.1	2.2 score on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period.

Average rhinoconjunctivitis DMS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis medication use (on a scale of 0-20). Higher scores indicate more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis DMS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
The Average Rhinoconjunctivitis Daily Medication Score (DMS) During the Primary Efficacy Assessment Period	1.8 score on a scale Standard Error 0.2	2.4 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: Week leading up to visit 7 (at the end of the primary efficacy assessment period, after approximately 52-57 weeks of treatment)

Population: Participants in the full analysis set with observations

The overall PRQLQ score measures the effect of rhinoconjunctivitis on participant's quality of life on a scale of 0-6. Higher scores indicate worse rhinoconjunctivitis-related quality of life.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=695 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=690 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Overall Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score at the End of Trial	0.8 score on a scale Standard Error 0.1	1.0 score on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants with asthma in the full analysis set with observations in the primary efficacy period

The average asthma DSS evaluates the treatment effect based on the reduction in daily asthma symptom score (on a scale of 0-12). Higher scores indicate more severe symptoms. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 asthma DSS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=251 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=280 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
The Average Asthma Daily Symptom Score (DSS) During the Primary Efficacy Assessment Period	0.3 score on a scale Standard Error 0.0	0.4 score on a scale Standard Error 0.0

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants with asthma in the full analysis set with observations in the primary efficacy period

The endpoint SABA free days evaluates the treatment effect based on the reduction in SABA use. The higher the proportion of SABA free days the higher the estimated probability of a participant having a day where they didn't use SABA.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=251 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=280 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
SABA Free Days During the Primary Efficacy Assessment Period	99.2 Probability (%) of a SABA free day Interval 98.6 to 99.6	98.6 Probability (%) of a SABA free day Interval 97.7 to 99.2

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants with asthma in the full analysis set with observations in the primary efficacy period.

Average weekly number of puffs of as-needed SABA use evaluates the treatment effect based on the reduction in the use of asthma reliever medication (SABA), and is calculated as 7 times the average of the daily number of puffs of as-needed SABA use. Higher values indicate more medication use.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=251 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=280 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Weekly Number of Puffs of As-needed SABA Use During the Primary Efficacy Assessment Period	1.0 weekly number of puffs Standard Error 0.2	1.5 weekly number of puffs Standard Error 0.2

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants with asthma in the full analysis set with observations in the primary efficacy period

The endpoint rhinitis mild days evaluates the treatment effect based on days when participants have no symptoms or mild symptoms and no medication use. The higher the proportion of rhinitis mild days the higher the estimated probability of a participant having a rhinitis mild day.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Rhinitis Mild Days During the Primary Efficacy Assessment Period	31.8 Probability (%) of a rhinitis mild day Interval 22.6 to 42.8	20.9 Probability (%) of a rhinitis mild day Interval 14.2 to 29.7

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period

The endpoint rhinitis exacerbation days evaluates the treatment effect based on days when participants have severe symptoms. The higher the proportion of rhinitis mild days the higher the estimated probability of a participant having a rhinitis exacerbation day.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Rhinitis Exacerbation Days During the Primary Efficacy Assessment Period	2.5 Probability (%) of a rhinitis exace. day Interval 1.7 to 3.6	4.4 Probability (%) of a rhinitis exace. day Interval 3.1 to 6.2

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period.

Average rhinitis CSMS evaluates the treatment effect based on the reduction in daily rhinitis symptoms and/or medication use. For this endpoint, the rhinitis symptoms and medication use were scored using an alternative method as recommended by EAACI (European Academy of Allergy \& Clinical Immunology) (on a scale of 0-5). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinitis CSMS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Average Rhinitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period	0.8 score on a scale Standard Error 0.1	1.0 score on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: 8 weeks (primary efficacy assessment period), which started 44-49 weeks after initiation of IMP

Population: Participants in the full analysis set with observations in the primary efficacy period.

Average rhinoconjunctivitis CSMS evaluates the treatment effect based on the reduction in daily rhinoconjunctivitis symptoms and/or medication use. For this endpoint, the rhinoconjunctivitis symptoms and medication use were scored using an alternative method as recommended by EAACI (European Academy of Allergy \& Clinical Immunology) (on a scale of 0-5). Higher scores indicate more severe symptoms and/or more medication use. The endpoint is calculated as the average score of all reported daily values during the 8-week primary efficacy assessment period. For example, if a subject reported 56 rhinoconjunctivitis CSMS values, the endpoint is calculated as the average of those values.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=693 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=706 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Average Rhinoconjunctivitis Combined Symptom and Medication Score (CSMS) During the Primary Efficacy Assessment Period	0.7 score on a scale Standard Error 0.1	0.9 score on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)

Population: Participants from Canada and Poland in the full analysis set with observations

House dust mite specific IgE reflects the allergen-specific allergy immunotherapy-induced immune modulation

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=178 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=184 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
House Dust Mite Specific IgE Dermatophagoides pteronyssinus specific IgE	0.2 log10 transformed kU/L Standard Deviation 0.3	0.0 log10 transformed kU/L Standard Deviation 0.2
House Dust Mite Specific IgE Dermatophagoides farinae specific IgE	0.3 log10 transformed kU/L Standard Deviation 0.3	0.0 log10 transformed kU/L Standard Deviation 0.2

SECONDARY outcome

Timeframe: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)

Population: Participants from Canada and Poland in the full analysis set with observations

House dust mite specific IgG4 reflects the allergen-specific allergy immunotherapy-induced immune modulation

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=178 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=184 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
House Dust Mite Specific IgG4 Dermatophagoides pteronyssinus specific IgG4	0.6 log10 transformed mg/L Standard Deviation 0.4	0.0 log10 transformed mg/L Standard Deviation 0.1
House Dust Mite Specific IgG4 Dermatophagoides farinae specific IgG4	0.7 log10 transformed mg/L Standard Deviation 0.4	0.0 log10 transformed mg/L Standard Deviation 0.2

SECONDARY outcome

Timeframe: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)

Population: Participants from Canada and Poland in the full analysis set with observations

The change in total IgE was measured from screening to the end of trial.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=178 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=183 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
Total IgE	0.2 log10 transformed kU/L Standard Deviation 0.3	0.0 log10 transformed kU/L Standard Deviation 0.2

SECONDARY outcome

Timeframe: Change from screening to the end of trial (after approximately 52-57 weeks of treatment)

Population: Participants from Canada and Poland in the full analysis set with observations

The IgE-blocking factor assesses the effect of serum components (including IgE-blocing antibodies known to be induced by allergy immunotherapy) competing with IgE for binding to allergen. IgE-blocking factor is calculated as 1-(S/T), where S is the amount of allergen-specific IgE bound to allergen in the (possible) presence of competing components, and where T is the total amount of allergen-specific IgE capable of binding to allergen when all competing antibodies/components have been washed off. IgE-blocking factor values closer to 0 indicate the presence of fewer IgE-blocking components and values closer to 1 indicate that more IgE is blocked from binding to the allergen.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=103 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily house dust mite sublingual immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=140 Participants Rhinitis/rhinoconjunctivitis rescue medication as needed, plus daily placebo sublingual immunotherapy tablet (Placebo SLIT-tablet).
House Dust Mite IgE-Blocking Factor	0.4 unitless Standard Deviation 0.3	-0.0 unitless Standard Deviation 0.1

Adverse Events

HDM SLIT-tablet (12 SQ-HDM)

Serious events: 16 serious events

Other events: 608 other events

Deaths: 0 deaths

Placebo SLIT-tablet

Serious events: 6 serious events

Other events: 534 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Vice President, Clinical Operations Strategy

ALK-Abelló A/S

Phone: +45 4574 7576

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No publication can be made before the primary publication. PI shall provide Sponsor (S) with a copy of any publication or presentation 60 days before submission/public disclosure. S can require changes or non-publication of the article, if appropriate. Upon S request, the PI must delay the publication, presentation or public disclosure for an additional 120 days to permit S to apply for a patent application. Any other public statements regarding the trial requires prior written consent from S.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	HDM SLIT-tablet (12 SQ-HDM) n=727 participants at risk Rhinitis/rhinoconjunctivitis rescue medication and asthma controller/reliever medication as needed, plus daily house dust mite sublingual allergy immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=731 participants at risk Rhinitis/rhinoconjunctivitis rescue medication and asthma controller/reliever medication as needed, plus daily placebo sublingual allergy immunotherapy tablet (Placebo SLIT-tablet).
Infections and infestations Gastroenteritis norovirus	0.28% 2/727 • Number of events 2 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations COVID-19	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Campylobacter gastroenteritis	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Influenza	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Laryngitis	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Pneumonia	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.27% 2/731 • Number of events 2 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Pseudomonas bronchitis	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Tonsillitis	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Appendicitis	0.00% 0/727 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.14% 1/731 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Nasopharyngitis	0.00% 0/727 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.14% 1/731 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Injury, poisoning and procedural complications Contusion	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Injury, poisoning and procedural complications Fracture	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Injury, poisoning and procedural complications Carbon monoxide poisoning	0.00% 0/727 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.14% 1/731 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Psychiatric disorders Attention deficit hyperactivity disorder	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Psychiatric disorders Hallucinations, mixed	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Nausea	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Vomiting	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
General disorders Non-cardiac chest pain	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Immune system disorders Immune system disorder	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Skin and subcutaneous tissue disorders Angioedema	0.14% 1/727 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.00% 0/731 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Reproductive system and breast disorders Testicular torsion	0.00% 0/727 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	0.14% 1/731 • Number of events 1 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.

Other adverse events
Measure	HDM SLIT-tablet (12 SQ-HDM) n=727 participants at risk Rhinitis/rhinoconjunctivitis rescue medication and asthma controller/reliever medication as needed, plus daily house dust mite sublingual allergy immunotherapy tablet (HDM-SLIT tablet, 12 SQ-HDM dose).	Placebo SLIT-tablet n=731 participants at risk Rhinitis/rhinoconjunctivitis rescue medication and asthma controller/reliever medication as needed, plus daily placebo sublingual allergy immunotherapy tablet (Placebo SLIT-tablet).
Gastrointestinal disorders Oral pruritus	57.6% 419/727 • Number of events 1149 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	25.3% 185/731 • Number of events 425 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Abdominal pain upper	33.4% 243/727 • Number of events 512 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	22.4% 164/731 • Number of events 320 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Lip swelling	20.8% 151/727 • Number of events 282 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	5.2% 38/731 • Number of events 63 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Glossodynia	19.5% 142/727 • Number of events 313 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	5.6% 41/731 • Number of events 54 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Nausea	18.6% 135/727 • Number of events 260 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	11.1% 81/731 • Number of events 125 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Mouth swelling	13.6% 99/727 • Number of events 210 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	3.7% 27/731 • Number of events 41 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Swollen tongue	13.6% 99/727 • Number of events 203 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	2.7% 20/731 • Number of events 29 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Diarrhoea	13.1% 95/727 • Number of events 151 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	10.1% 74/731 • Number of events 107 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Mouth ulceration	12.8% 93/727 • Number of events 162 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	7.3% 53/731 • Number of events 80 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Tongue ulceration	6.9% 50/727 • Number of events 82 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	3.7% 27/731 • Number of events 34 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Vomiting	6.6% 48/727 • Number of events 76 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	4.5% 33/731 • Number of events 38 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Gastrointestinal disorders Tooth loss	5.5% 40/727 • Number of events 66 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	4.8% 35/731 • Number of events 61 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Respiratory, thoracic and mediastinal disorders Throat irritation	55.2% 401/727 • Number of events 1072 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	32.3% 236/731 • Number of events 504 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Respiratory, thoracic and mediastinal disorders Pharyngeal swelling	9.4% 68/727 • Number of events 134 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	3.0% 22/731 • Number of events 33 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Respiratory, thoracic and mediastinal disorders Asthma	1.9% 14/727 • Number of events 16 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	5.2% 38/731 • Number of events 49 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Nasopharyngitis	25.4% 185/727 • Number of events 250 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	22.4% 164/731 • Number of events 206 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations COVID-19	5.2% 38/727 • Number of events 38 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	5.2% 38/731 • Number of events 38 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Pharyngitis	5.2% 38/727 • Number of events 44 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	5.1% 37/731 • Number of events 49 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Bronchitis	5.0% 36/727 • Number of events 42 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	6.2% 45/731 • Number of events 52 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Infections and infestations Upper respiratory tract infection	3.0% 22/727 • Number of events 29 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	5.1% 37/731 • Number of events 53 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Ear and labyrinth disorders Ear pruritus	33.3% 242/727 • Number of events 547 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	18.5% 135/731 • Number of events 299 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.
Nervous system disorders Taste disorder	16.9% 123/727 • Number of events 213 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.	15.9% 116/731 • Number of events 218 • Adverse events (AEs) were collected from consent until the last follow-up phone contact with the participant (from V1 to TC3 (telephone call 3), for approximately 54-59 weeks). Treatment emergent AEs (TEAEs) are displayed (these were AEs starting on/after time of first IMP and no later than 7 days after last day of IMP). For the first 28 days of treatment, the presence/absence of 15 specific symptoms, identified as local side effects of sublingual immunotherapy (solicited events), were captured in an eDiary. Solicited events were evaluated by the investigator and reported in the eCRF as AEs as per their discretion. TEAEs from the eCRF are presented.