Trial Outcomes & Findings for Mite Asthma Pediatric Immunotherapy Trial (NCT NCT03654976)

Last Updated: 2023-10-19

Results Overview

The primary endpoint of the trial was the annualized rate of clinically relevant asthma exacerbations calculated as the number of exacerbations per year per participant during the efficacy evaluation period of 20 months. A clinically relevant asthma exacerbation had to be medically confirmed and was defined as asthma worsening leading to at least 1 of the following criteria: * Doubling of ICS dose compared to background treatment * Systemic corticosteroids for treatment of asthma symptoms for at least 3 days * Emergency room visit due to asthma, requiring systemic corticosteroids * Hospitalization for more than 12 hours due to asthma, requiring treatment with systemic corticosteroids The outcome measure (by treatment group) is an adjusted annualized rate of clinically relevant asthma exacerbations.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

533 participants

Primary outcome timeframe

Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)

Results posted on

2023-10-19

Participant Flow

The trial had randomized participants from 64 sites in 9 countries (Bulgaria, France, Germany, Hungary, Poland, Russia, Spain, United Kingdom, US).

Participant milestones

Participant milestones
Measure	HDM SLIT-tablet (12 SQ-HDM) Participant's daily background asthma medication of low dose inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) or medium/high dose ICS with or without LABA, reliever asthma medication of short-acting beta-agonist (SABA) as needed plus 1 daily house dust mite (HDM) sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Overall Study STARTED	270	263
Overall Study Completed IMP	239	242
Overall Study Full Analysis Set	264	260
Overall Study Safety Analysis Set	270	263
Overall Study COMPLETED	241	245
Overall Study NOT COMPLETED	29	18

Reasons for withdrawal

Reasons for withdrawal
Measure	HDM SLIT-tablet (12 SQ-HDM) Participant's daily background asthma medication of low dose inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) or medium/high dose ICS with or without LABA, reliever asthma medication of short-acting beta-agonist (SABA) as needed plus 1 daily house dust mite (HDM) sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Overall Study Withdrawal by Subject	12	11
Overall Study Reason stated as 'Other' in CRF	10	6
Overall Study Adverse Event	5	0
Overall Study Lost to Follow-up	2	0
Overall Study Lack of Efficacy	0	1

Baseline Characteristics

Mite Asthma Pediatric Immunotherapy Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HDM SLIT-tablet (12 SQ-HDM) n=270 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=263 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet	Total n=533 Participants Total of all reporting groups
Age, Categorical <=18 years	270 Participants n=93 Participants	263 Participants n=4 Participants	533 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	10.6 years STANDARD_DEVIATION 3.4 • n=93 Participants	10.6 years STANDARD_DEVIATION 3.3 • n=4 Participants	10.6 years STANDARD_DEVIATION 3.4 • n=27 Participants
Age, Customized Children (5-11 years)	162 Participants n=93 Participants	154 Participants n=4 Participants	316 Participants n=27 Participants
Age, Customized Adolescents (12-17 years)	108 Participants n=93 Participants	109 Participants n=4 Participants	217 Participants n=27 Participants
Sex: Female, Male Female	88 Participants n=93 Participants	94 Participants n=4 Participants	182 Participants n=27 Participants
Sex: Female, Male Male	182 Participants n=93 Participants	169 Participants n=4 Participants	351 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=93 Participants	25 Participants n=4 Participants	44 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	238 Participants n=93 Participants	224 Participants n=4 Participants	462 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=93 Participants	14 Participants n=4 Participants	27 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=93 Participants	5 Participants n=4 Participants	11 Participants n=27 Participants
Race/Ethnicity, Customized White	259 Participants n=93 Participants	254 Participants n=4 Participants	513 Participants n=27 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Other	4 Participants n=93 Participants	4 Participants n=4 Participants	8 Participants n=27 Participants
Region of Enrollment Bulgaria	32 Participants n=93 Participants	33 Participants n=4 Participants	65 Participants n=27 Participants
Region of Enrollment France	13 Participants n=93 Participants	12 Participants n=4 Participants	25 Participants n=27 Participants
Region of Enrollment Germany	6 Participants n=93 Participants	5 Participants n=4 Participants	11 Participants n=27 Participants
Region of Enrollment Hungary	18 Participants n=93 Participants	19 Participants n=4 Participants	37 Participants n=27 Participants
Region of Enrollment Poland	146 Participants n=93 Participants	145 Participants n=4 Participants	291 Participants n=27 Participants
Region of Enrollment Russia	19 Participants n=93 Participants	19 Participants n=4 Participants	38 Participants n=27 Participants
Region of Enrollment Spain	20 Participants n=93 Participants	16 Participants n=4 Participants	36 Participants n=27 Participants
Region of Enrollment United Kingdom	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment United States	14 Participants n=93 Participants	12 Participants n=4 Participants	26 Participants n=27 Participants
Region West (DEU, ESP, FRA, GRB, USA)	55 Participants n=93 Participants	47 Participants n=4 Participants	102 Participants n=27 Participants
Region Central (POL)	146 Participants n=93 Participants	145 Participants n=4 Participants	291 Participants n=27 Participants
Region East (BGR, HUN, RUS)	69 Participants n=93 Participants	71 Participants n=4 Participants	140 Participants n=27 Participants

PRIMARY outcome

Timeframe: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)

Population: Participant from the full analysis set with observations in the efficacy assessment period.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=252 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=257 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Annualized Rate of Clinically Relevant Asthma Exacerbations	0.18 Exacerbations per year per participant Interval 0.13 to 0.25	0.21 Exacerbations per year per participant Interval 0.15 to 0.28

SECONDARY outcome

Timeframe: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)

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

The days with nocturnal awakenings due to asthma requiring SABA rescue medication were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months. The proportion of days with nocturnal awakenings due to asthma requiring SABA was presented on a range from 0 to 1 (1 indicating that all days in the eDiary period were with nocturnal awakenings due to asthma requiring SABA rescue medication). The efficacy assessment was based on data collected over the 20 months efficacy assessment period. The outcome measure (by treatment group) is an estimated proportion of days with nocturnal awakenings due to asthma requiring SABA rescue medication.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=253 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=259 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Proportion of Days With Nocturnal Awakenings Due to Asthma Requiring SABA Rescue Medication	0.0147 Proportion of days with awakenings Interval 0.0093 to 0.0233	0.0190 Proportion of days with awakenings Interval 0.0126 to 0.0287

SECONDARY outcome

Timeframe: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)

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

The days with SABA use were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months. The proportion of days with SABA use was presented on a range from 0 to 1 (1 indicating that all days in the eDiary period were with SABA use). The efficacy assessment was based on data collected over the 20 months efficacy assessment period. The outcome measure (by treatment group) is an estimated proportion of days with SABA use.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=253 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=259 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Proportions of Days With SABA Use	0.0943 Proportion of days with SABA use Interval 0.0694 to 0.1269	0.1094 Proportion of days with SABA use Interval 0.0855 to 0.1391

SECONDARY outcome

Timeframe: Efficacy assessment period was 20 months (following a 4-10 months treatment initiation and maintenance period)

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

The outcome measure (by treatment) is an average of the percentage predicted FEV1 measured at visits 5 to 11 (every 4 months during the 20 months efficacy assessment period), analyzed using MMRM (mixed-effect model repeated measurement). FEV1 (forced expired volume in 1 second) is assessed by use of spirometry and is a measure for lung function. Percentage predicted FEV1 is derived from the predicted FEV1, which is the expected value of FEV1 for a person of a certain age, race, height and gender with healthy lungs.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=254 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=259 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Percentage Predicted FEV1	97.17 Percentage predicted FEV1 Interval 96.02 to 98.32	97.05 Percentage predicted FEV1 Interval 95.82 to 98.28

SECONDARY outcome

Timeframe: Assessment done at the end of trial visit (after 24-30 months of treatment)

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

At the end of trial visit, the subject was asked, when compared to their asthma before IMP treatment, how they felt overall. Subjects who answered 'much better' or 'better' were categorized as having improved allergic asthma. At the end of trial visit, subjects had been treated for 24-30 months (including a 4-10 months treatment initiation and maintenance period). The outcome measure (by treatment) is an adjusted odds of experiencing improved allergic asthma.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=239 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=244 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Global Evaluation of Allergic Asthma as Having an Improved Outcome	14.66 Odds of improved allergic asthma Interval 8.3 to 25.89	6.48 Odds of improved allergic asthma Interval 4.03 to 10.43

SECONDARY outcome

Timeframe: Assessment done at the end of trial visit (after 24-30 months of treatment)

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

At the end of trial visit, the subject was asked, when compared to their rhinitis before IMP treatment, how they felt overall. Subjects who answered 'much better' or 'better' were categorized as having improved allergic rhinitis. At the end of trial visit, subjects had been treated for 24-30 months (including a 4-10 months treatment initiation and maintenance period). The outcome measure (by treatment) is an adjusted odds of experiencing improved allergic rhinitis.

Outcome measures

Outcome measures
Measure	HDM SLIT-tablet (12 SQ-HDM) n=239 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=244 Participants Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual tablet
Global Evaluation of Allergic Rhinitis as Having an Improved Outcome	8.29 Odds of improved allergic rhinitis Interval 5.35 to 12.85	5.11 Odds of improved allergic rhinitis Interval 3.49 to 7.48

OTHER_PRE_SPECIFIED outcome

Timeframe: The efficacy assessment period for the endpoint started 4 months after treatment initiation and lasted until the end of the trial or discontinuation of treatment (up to 24-30 months of treatment).

Allergic rhinitis symptoms were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months, for up to 24-30 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Allergic rhinitis medication use were entered in an eDiary by the participant/caregiver in a 2-week period every 4 months, for up to 24-30 months.

Outcome measures

Outcome data not reported

Adverse Events

HDM SLIT-tablet (12 SQ-HDM)

Serious events: 14 serious events

Other events: 250 other events

Deaths: 0 deaths

Placebo SLIT-tablet

Serious events: 12 serious events

Other events: 228 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director Global Clinical Development

ALK-Abelló A/S

Phone: 0045 45747576

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor shall be able to review any proposed publication or presentation at least 60 days in advance of submission. Sponsor cannot require changes. Upon sponsor's request, the investigator shall delay a publication or presentation for 6 months to permit the sponsor to take necessary steps to protect confidential information. For this multi-site trial it is mandatory that the primary publication is based on data from all trial sites analyzed as stipulated in the protocol and in the SAP.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	HDM SLIT-tablet (12 SQ-HDM) n=270 participants at risk Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=263 participants at risk Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual allergy immunotherapy tablet
Blood and lymphatic system disorders Lymphadenitis	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Eosinophilic oesophagitis	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Pancreatic disorder	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Bronchitis	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Infectious mononucleosis	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.76% 2/263 • Number of events 2 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Pneumonia	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Rhinovirus infection	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Salmonellosis	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Wound infection	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Injury, poisoning and procedural complications Skin wound	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Injury, poisoning and procedural complications Spinal compression fracture	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Musculoskeletal and connective tissue disorders Growth retardation	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Musculoskeletal and connective tissue disorders Scoliosis	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Psychiatric disorders Anorexia nervosa	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Psychiatric disorders Anxiety	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Renal and urinary disorders Haematuria	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Reproductive system and breast disorders Testicular cyst	0.00% 0/270 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.38% 1/263 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 4/270 • Number of events 4 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	1.5% 4/263 • Number of events 5 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.37% 1/270 • Number of events 1 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	0.00% 0/263 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.

Other adverse events
Measure	HDM SLIT-tablet (12 SQ-HDM) n=270 participants at risk Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily HDM sublingual allergy immunotherapy tablet (12 SQ-HDM)	Placebo SLIT-tablet n=263 participants at risk Participant's daily background asthma medication of low dose ICS plus LABA or medium/high dose ICS with or without LABA, reliever asthma medication of SABA as needed plus 1 daily placebo sublingual allergy immunotherapy tablet
Ear and labyrinth disorders Ear pruritus	38.5% 104/270 • Number of events 257 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	22.8% 60/263 • Number of events 124 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Eye disorders Conjunctivitis allergic	5.2% 14/270 • Number of events 19 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	4.6% 12/263 • Number of events 13 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Abdominal pain upper	43.7% 118/270 • Number of events 231 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	38.4% 101/263 • Number of events 194 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Aphthous ulcer	5.9% 16/270 • Number of events 28 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	6.5% 17/263 • Number of events 28 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Diarrhoea	22.2% 60/270 • Number of events 96 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	19.4% 51/263 • Number of events 77 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Glossodynia	27.4% 74/270 • Number of events 134 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	6.8% 18/263 • Number of events 23 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Lip swelling	26.3% 71/270 • Number of events 154 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	5.3% 14/263 • Number of events 18 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Mouth swelling	24.8% 67/270 • Number of events 159 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	4.2% 11/263 • Number of events 16 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Mouth ulceration	9.6% 26/270 • Number of events 44 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	6.1% 16/263 • Number of events 17 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Nausea	31.5% 85/270 • Number of events 167 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	21.7% 57/263 • Number of events 96 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Oral pruritus	64.8% 175/270 • Number of events 475 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	24.7% 65/263 • Number of events 126 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Swollen tongue	20.4% 55/270 • Number of events 98 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	3.0% 8/263 • Number of events 8 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Tongue ulceration	7.0% 19/270 • Number of events 34 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	3.4% 9/263 • Number of events 15 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Gastrointestinal disorders Vomiting	12.2% 33/270 • Number of events 49 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	5.3% 14/263 • Number of events 19 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Corona virus infection	6.7% 18/270 • Number of events 18 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	5.3% 14/263 • Number of events 14 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Nasopharyngitis	23.3% 63/270 • Number of events 110 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	21.7% 57/263 • Number of events 95 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Pharyngitis	7.8% 21/270 • Number of events 28 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	5.7% 15/263 • Number of events 21 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Upper respiratory tract infection	9.6% 26/270 • Number of events 38 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	9.5% 25/263 • Number of events 31 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Viral infection	6.7% 18/270 • Number of events 18 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	6.8% 18/263 • Number of events 22 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Nervous system disorders Dysgeusia	20.0% 54/270 • Number of events 120 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	16.7% 44/263 • Number of events 68 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Nervous system disorders Headache	5.9% 16/270 • Number of events 17 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	4.2% 11/263 • Number of events 13 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Asthma	29.6% 80/270 • Number of events 158 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	36.5% 96/263 • Number of events 176 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 15/270 • Number of events 19 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	7.6% 20/263 • Number of events 24 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	21.5% 58/270 • Number of events 113 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	5.3% 14/263 • Number of events 23 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	5.9% 16/270 • Number of events 27 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	8.7% 23/263 • Number of events 47 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Respiratory, thoracic and mediastinal disorders Throat irritation	61.5% 166/270 • Number of events 494 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	35.7% 94/263 • Number of events 178 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
General disorders Pyrexia	4.4% 12/270 • Number of events 14 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	6.5% 17/263 • Number of events 19 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Bronchitis	4.4% 12/270 • Number of events 17 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	8.0% 21/263 • Number of events 29 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.
Infections and infestations Influenza	4.4% 12/270 • Number of events 14 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.	5.3% 14/263 • Number of events 16 • AEs were collected from consent to last follow-up phone contact (up to 24-30 months of treatment). 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 included in TEAEs presented.