Download PDF

Clinical Trial Results:
A multicenter randomized double-blind placebo-controlled clinical trial for evaluation of efficacy and safety of specific immunotherapy with an aluminium hydroxide-adsorbed allergoid preparation of house dust mite (Dermatophagoides pteronyssinus) in patients with allergic bronchial asthma and with allergic rhinitis or rhinoconjunctivitis

Summary
EudraCT number	2015-000188-15
Trial protocol	PL LT DE ES LV AT HR
Global end of trial date	25 Apr 2019

Results information
Results version number	v1(current)
This version publication date	11 Nov 2020
First version publication date	11 Nov 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

AL1402ac

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Allergopharma GmbH & Co. KG

Sponsor organisation address

Hermann-Körner-Straße 52, Reinbek, Germany, 21465

Public contact

Clinical Trials Information, Allergopharma GmbH & Co. KG, +49 40 727 65 - 0,

Scientific contact

Clinical Trials Information, Allergopharma GmbH & Co. KG, +49 40 727 65 - 0,

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000835-PIP01-10

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

24 Jul 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 Apr 2019

Was the trial ended prematurely?

Main objective of the trial

to demonstrate efficacy and to evaluate safety of AIT with an aluminium hydroxide adsorbed allergoid preparation of major allergens of D.p. in patients with allergic bronchial asthma (GINA 2016; steps 2 to 4) and allergic rhinitis or rhinoconjunctivitis caused by house dust mites.

Protection of trial subjects

The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with the International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use (ICH) guidance for Good Clinical Practice (GCP) and the applicable regulatory requirements. Data Safety Monitoring Board (DSMB ) was in place throughout the trial; DSMB consisted of 3 independent experts, experienced in the field of allergy. The primary function of the DSMB was to ensure the subjects’ safety. The DSMB team reviewed an update of the safety data from all treated subjects. After each administration of the IMP, each subject in the study was kept under supervision of a qualified and trained investigator for at least 30 min. Safety evaluation during supervision after IMP administration consisted of: FEV1, Systolic BP, Diastolic BP, Heart rate (Pulse rate), Respiratory rate.

Background therapy

Evidence for comparator

- Abbreviations used in this document: ACQ=Asthma Quality of Life Questionnaire AE=Adverse Event AIT=Allergen Immunotherapy ALAT=Alanine Aminotransferase AQLQ=Asthma Quality of Life Questionnaire ASAT=Aspartate Aminotransferase BMI=Body Mass Index BP=Blood Pressure bpm=Beats per Minute CS=Clinically Significant CSMS=Combined Symptom Medication Score D.f.=Dermatophagoides Farinae D.p.=Dermatophagoides Pteronyssinus DSMB=Data Safety Monitoring Board dMS=Daily Medication Score dSS=Daily Symptom Score EAACI=European Academy of Allergy and Clinical Immunology FEV1=Forced Expiratory Volume in 1 Second γ-GT=Gamma Glutamyl Transferase GCP=Good Clinical Practice GINA=Global Initiative for Asthma ICF=Informed Consent Form ICS=Inhaled Corticosteroid Ig=Immunoglobulin kU/L=kilo Units per Litre IMP=Investigational Medicinal Product IS=Injection Site MedDRA=Medical Dictionary for Regulatory Activities NCS=Not Clincally Significant PEF=Peakflow PNU=Protein Nitrogen Unit RBC=Red Blood Cells rdss=Rhinitis Daily Symptom Score SABA=Short Acting Beta Agonist SPT=Skin Prickt Test T=Treatment TEAE=Treatment Emergent Adverse event TU=Therapeutic Units WAO=World Allergy Organization

Actual start date of recruitment

01 Mar 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 216

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

Croatia: 2

Country: Number of subjects enrolled

Austria: 21

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Latvia: 40

Country: Number of subjects enrolled

Lithuania: 13

Country: Number of subjects enrolled

Romania: 27

Country: Number of subjects enrolled

Serbia: 50

Country: Number of subjects enrolled

Ukraine: 43

Country: Number of subjects enrolled

Russian Federation: 9

Worldwide total number of subjects

424

EEA total number of subjects

322

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

122

Adults (18-64 years)

302

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Overall, 1038 male and female subjects (12 to 65 y) were screened for eligibility; of these, 426 were randomised to treatment according to the exclusion and inclusion criteria.

Screening details

Study subjects (outpatients) were included if they were suffering from immunoglobulin (Ig) E-mediated allergic bronchial asthma according to GINA step 2-4, caused by house dust mite documented by skin prick test (SPT) wheal for Dermatophagoides pteronyssinus (D.p.) and specific IgE value of ≥ 1.50 kU/L to D.p.

Number of subjects started

1038 ^[1]

Number of subjects completed

424

Reason: Number of subjects

Sponsor/DSMB decision: 10

Reason: Number of subjects

Consent withdrawn by subject: 49

Reason: Number of subjects

Pregnancy: 3

Reason: Number of subjects

Adverse event, non-fatal: 3

Reason: Number of subjects

Lost to follow-up: 4

Reason: Number of subjects

Missing reason: 1

Reason: Number of subjects

Other reasons: 7

Reason: Number of subjects

Inclusion/ exclusion criteria: 537

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The number of subjects: - enrolled worldwide is 1038 - subjects enrolled per country are given for the Safety Set of 424 patient

Period 1 title

Treatmant (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo: solution containing aluminium hydroxide (Al(OH)3) in normal saline (9 g/L sodium chloride) was applied. Injection volume (0.1 mL at minimum 0.6 mL at maximum for matching Strength A placebo and 0.1 - 0.6 mL strength B placebo) was matching the volume of the corresponding active preparation. The injections were administered slowly, strictly subcutaneously, under sterile precautionary measures, on the extensor side of the upper arm, a hand’s breadth above the elbow, using a short-ground cannula. After each administration at the trial center, the patient was kept under close supervision for at least 30 minutes.

Acaroid

Arm description

Arm type

Experimental

Investigational medicinal product name

D. pteronyssinus allergoid preparation 5400 PNU

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

D. pteronyssinus allergoid preparation 5400 PNU For the injection volume and administration details of the active treatment, please see the description above for Placebo. PNU=Protein nitrogen unit

Number of subjects in period 1	Placebo	Acaroid
Started	134	290
Completed	127	272
Not completed	7	18
Consent withdrawn by subject	3	4
Adverse event, non-fatal	-	7
Pregnancy	2	1
Other reasons	1	3
Lost to follow-up	-	2
Sponsor/DSMB decision	1	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Acaroid

Reporting group description

Reporting group values	Placebo	Acaroid	Total
Number of subjects	134	290	424
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	36	86	122
Adults (18-64 years)	98	204	302
From 65-84 years	0	0	0
85 years and over	0	0	0
Adolescents	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	28.5 ( 12.6 )	27.1 ( 11.9 )	-
Gender categorical
Units: Subjects
Female	69	139	208
Male	65	151	216
Race
Units: Subjects
Caucasian	132	287	419
Asian descent	2	3	5

End points

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Acaroid

Reporting group description

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

This was a multicenter, multinational, double-blind, placebo-controlled trial with 2 parallel groups. It was a confirmatory phase III pivotal trial with one primary efficacy endpoint to confirm the efficacy of Acaroid for the treatment of allergic asthma when comparing the dose of 5400 protein nitrogen unit (PNU) to placebo. Adolescent and adult patients with allergic bronchial asthma and allergic rhinitis or rhinoconjunctivitis caused by house dust mites were randomized 2:1 to treatment with Acaroid® or placebo for approximately 8 months. The trial consisted of a screening period, a baseline period, a treatment period, and an eDiary period after treatment. In the baseline period, the necessity of inhaled corticosteroids (ICS) for treating asthma and the minimal dose of ICS required to achieve asthma control were evaluated.

Subject analysis set title

Acaroid

Subject analysis set type

Full analysis

Subject analysis set description

Primary: 1_Change of minimal controlled dose (multiple imputation)

Top of page

End point title

1_Change of minimal controlled dose (multiple imputation)

End point description

This was a confirmatory phase III pivotal trial: The primary objective was to confirm efficacy of Acaroid in the treatment of allergic asthma when comparing to placebo. Primary endpoint was the change in dose steps of the minimum daily inhaled corticosteroid (ICS) dose required to ensure asthma control (well controlled or partly controlled [ACQ 6 score ≤ 1.00]) according to the Asthma Control Questionnaire (ACQ6) between baseline and after Allergen Immunotherapy.

End point type

Primary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Subjects
Increase by 3 steps (+3)	0	1
Increase by 2 steps (+2)	1	0
Increase by 1 step (+1)	1	6
No change	25	38
Reduction by 1 step (-1)	33	64
Reduction by 2 steps (-2)	37	97
Reduction by 3 steps (-3)	24	46
Reduction by 4 steps (-4)	2	12
Missing (imputed)	9	22

Primary efficacy analysis

Statistical analysis description

To derive the p-value for the hypothesis, the one-sided stratified Mann-Whitney U-test, also known as van-Elteren-test (van Elteren 1960)was performed with the stratification variables ‘pooled country’ and ‘age group’ (adolescents [12-17 years] and adults [≥18 years]). No continuity correction was to be done.

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9311 ^[1]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[1] - One sided stratified Mann-Whitney U-test by pooled country and age group comparing active vs. placebo- multiple imputation.

Secondary: 2_1_Minimal controlled dose [μg] – summary statistics

Top of page

End point title

2_1_Minimal controlled dose [μg] – summary statistics

End point description

The change of the minimum daily ICS (Budesonide) dose required to ensure asthma control was analyzed as continuous variable.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: μg
arithmetic mean (standard deviation)	-404.9 ( 309.1 )	-455.0 ( 325.7 )

No statistical analyses for this end point

Secondary: 2_2_Change of minimal controlled ICS dose [μg]

Top of page

End point title

2_2_Change of minimal controlled ICS dose [μg]

End point description

The requirement of the minimum daily ICS (Budesonide) dose to ensure asthma control was analyzed in categories of 200µg (range: -1200 to +800µg).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Subjects
-1200	2	12
-1000	2	7
-800	24	45
-600	11	27
-400	41	110
-200	16	18
'0'	25	38
400	1	5
800	0	0
Missing	10	24

Change of minimal controlled dose [μg]

Statistical analysis description

The one-sided stratified Mann-Whitney U-test was used to compare the distributions of the change from baseline to post-treatment as categorical variable.

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

= 0.0297 ^[3]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[2] - Frequency table
[3] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo - observed cases

Secondary: 3_1_ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

3_1_ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the mean score of all questions and ranges from 0 (no impairment) to 6 (maximum impairment). ACQ6 score was recorded as described in (Barnes P et al., Allergy 2014[69]: 1119-1140).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-1.142 ( 0.723 )	-1.183 ( 0.701 )

No statistical analyses for this end point

Secondary: 3_2_ANCOVA for change of ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

3_2_ANCOVA for change of ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the mean score of all questions and ranges from 0 (no impairment) to 6 (maximum impairment).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-1.067 ( 0.053 )	-1.155 ( 0.039 )

ANCOVA change ACQ6 score at highest daily ICSdose

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1148 ^[4]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.089

Confidence interval

level

95%

sides

2-sided

lower limit

-0.199

upper limit

0.022

Notes
[4] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 3_3_Categorical display of mean ACQ6 score under the lowest daily ICS dose the patient was controlled at post-treatment

Top of page

End point title

3_3_Categorical display of mean ACQ6 score under the lowest daily ICS dose the patient was controlled at post-treatment

End point description

Analysis of categorized ACQ6 score values.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Subjects
ACQ6 = 0 for minimal controlled dose after AIT	37	92
0<ACQ6≤0.5 for minimal controlled dose after AIT	49	103
ACQ6 > 0.5 for minimal controlled dose after AIT	36	65
Missing	10	26

Categorical display of mean ACQ6 score

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.8481 ^[6]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[5] - Frequency table
[6] - One sided stratified Mann-Whitney U-test by pooled country and age group comparing active vs. placebo - observed cases

Secondary: 4_1_Night time awakening with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

4_1_Night time awakening with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (never) to 6 (unable to sleep because of asthma).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-1.04 ( 1.12 )	-0.96 ( 1.07 )

No statistical analyses for this end point

Secondary: 4_2_ANCOVA for change of night time awakening with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

4_2_ANCOVA for change of night time awakening with the highest daily ICS dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (never) to 6 (unable to sleep because of asthma).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-0.88 ( 0.06 )	-0.95 ( 0.04 )

ANCOVA for change of night time awakening

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2723 ^[7]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.05

Notes
[7] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 5_1_Severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline – summary statistics

Top of page

End point title

5_1_Severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline – summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the mean score of all questions and ranges from 0 (no symptoms) to 6 (very severe symptoms).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-1.31 ( 1.15 )	-1.47 ( 1.01 )

No statistical analyses for this end point

Secondary: 5_2_ANCOVA for change of severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

5_2_ANCOVA for change of severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (no symptoms) to 6 (very severe symptoms).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-1.39 ( 0.08 )	-1.46 ( 0.06 )

ANCOVA for change of severity of asthma symptoms

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4565 ^[8]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.1

Notes
[8] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 6_1_Limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

6_1_Limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (not limited at all) to 6 (totally limited).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-1.34 ( 1.07 )	-1.35 ( 1.08 )

No statistical analyses for this end point

Secondary: 6_2_ANCOVA for change of limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

6_2_ANCOVA for change of limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (not limited at all) to 6 (totally limited).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-1.26 ( 0.08 )	-1.31 ( 0.06 )

ANCOVA change of limitation of daily activities

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5224 ^[9]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.11

Notes
[9] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 7_1_Shortness of breath with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

7_1_Shortness of breath with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (none) to 6 (a very great deal).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-1.40 ( 1.10 )	-1.48 ( 1.08 )

No statistical analyses for this end point

Secondary: 7_2_ANCOVA for change of shortness of breath with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

7_2_ANCOVA for change of shortness of breath with the highest daily ICS dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (none) to 6 (a very great deal).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-1.27 ( 0.08 )	-1.45 ( 0.06 )

ANCOVA for change of shortness of breath

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0222 ^[10]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

-0.03

Notes
[10] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 8_1_Wheezing with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

8_1_Wheezing with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (not at all) to 6 (all the time).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-1.09 ( 1.07 )	-1.10 ( 1.08 )

No statistical analyses for this end point

Secondary: 8_2_ANCOVA for change of wheezing with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

8_2_ANCOVA for change of wheezing with the highest daily ICS dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (not at all) to 6 (all the time).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-0.99 ( 0.07 )	-1.05 ( 0.05 )

ANCOVA for change of wheezing

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4677 ^[11]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.09

Notes
[11] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 9_1_Number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

9_1_Number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline - summary statistics

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (none) to 6 (more than 16 puffs/inhalations most days).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
arithmetic mean (standard deviation)	-0.66 ( 0.89 )	-0.74 ( 0.95 )

No statistical analyses for this end point

Secondary: 9_2_ANCOVA for change of number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline

Top of page

End point title

9_2_ANCOVA for change of number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline

End point description

Analysis of ACQ6 score values. The outcome was calculated as the scores and ranged from 0 (none) to 6 (mor than 16 puffs/inhalations most days).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	117	245
Units: Score
least squares mean (standard error)	-0.60 ( 0.06 )	-0.70 ( 0.04 )

ANCOVA for change of number of inhalations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

362

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1104 ^[12]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.02

Notes
[12] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 10_1_Outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

10_1_Outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

Change in outcome of the Quality of Life Questionnaire (Mini-AQLQ; Juniper et al., Eur Resp J 1999; 14(1): 32-38) with the highest daily ICS dose the patient was not controlled at baseline (was not available for Croatia and Romania). The outcome was calculated as the mean score of all questions and ranges from 1 (worse) to 7 (best).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	78	169
Units: Score
arithmetic mean (standard deviation)	1.054 ( 1.008 )	1.047 ( 0.961 )

No statistical analyses for this end point

Secondary: 10_2_ANCOVA for change of outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

10_2_ANCOVA for change of outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline

End point description

Change in outcome of the Quality of Life Questionnaire (Mini-AQLQ) with the highest daily ICS dose the patient was not controlled at baseline (was not available for Croatia and Romania). The outcome was calculated as the mean score of all questions and ranges from 1 (worse) to 7 (best).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	78	169
Units: Score
least squares mean (standard error)	0.904 ( 0.089 )	1.042 ( 0.063 )

ANCOVA for change of outcome of Mini-AQLQ

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

247

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1171 ^[13]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

0.138

Confidence interval

level

95%

sides

2-sided

lower limit

-0.035

upper limit

0.31

Notes
[13] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 11_1_Mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline - summary statistcs

Top of page

End point title

11_1_Mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline - summary statistcs

End point description

Mean pre-bronchodilator morning peak flow [L/min]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	112	233
Units: L/min
arithmetic mean (standard deviation)	17.85 ( 73.00 )	11.16 ( 60.69 )

No statistical analyses for this end point

Secondary: 11_2_ANCOVA for change of mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

11_2_ANCOVA for change of mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline

End point description

ANCOVA for change mean prebronchodilator morning peak flow [L/min]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	112	233
Units: L/min
least squares mean (standard error)	15.59 ( 6.81 )	10.24 ( 4.96 )

ANCOVA for change of mean pre-bronchodilator

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

345

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4528 ^[14]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-5.35

Confidence interval

level

95%

sides

2-sided

lower limit

-19.36

upper limit

8.65

Notes
[14] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 12_1_Patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline - summary statistics

Top of page

End point title

12_1_Patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline - summary statistics

End point description

Mean FEV1 value [L/s]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	8	20
Units: L/s
arithmetic mean (standard deviation)	-0.043 ( 0.580 )	0.232 ( 0.401 )

No statistical analyses for this end point

Secondary: 12_2_ANCOVA for change of patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline

Top of page

End point title

12_2_ANCOVA for change of patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline

End point description

ANCOVA for change of mean FEV1 value [L/s]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	8	20
Units: L/s
least squares mean (standard error)	0.053 ( 0.214 )	0.324 ( 0.130 )

ANCOVA for change of patient's mean FEV1

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.185 ^[15]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

0.272

Confidence interval

level

95%

sides

2-sided

lower limit

-0.141

upper limit

0.685

Notes
[15] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 13_1_Relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Top of page

End point title

13_1_Relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

End point description

A symptom free day was defined as a day where no asthma symptoms were entered into the Diary. The relative number of symptom free days was to be calculated as the number of symptom free days divided by the number of days where the corresponding questions were answered within the first week the highest uncontrolled ICS dose was administered.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	84	175
Units: Number
arithmetic mean (standard deviation)	0.376 ( 0.472 )	0.509 ( 0.455 )

No statistical analyses for this end point

Secondary: 13_2_ANCOVA for change in relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline

Top of page

End point title

13_2_ANCOVA for change in relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline

End point description

A symptom free day was defined as a day where no asthma symptoms were entered into the eDiary. The relative number of symptom free days was to be calculated as the number of symptom free days divided by the number of days where the corresponding questions were answered within the first week the highest uncontrolled ICS dose was administered.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	84	175
Units: Number
least squares mean (standard error)	0.357 ( 0.052 )	0.484 ( 0.038 )

ANCOVA change relative number of symptom free days

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0218 ^[16]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

0.127

Confidence interval

level

95%

sides

2-sided

lower limit

0.019

upper limit

0.236

Notes
[16] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 14_1_Rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Top of page

End point title

14_1_Rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

End point description

Rhinitis and conjunctivitis symptoms and medication were recorded using daily eDiary questions at baseline, during and after treatment evaluated as described in: EAACI Position Paper (Pfaar et al. 2014; Allergy 69: 854–867). The questionnaire consisted of 4 questions for rhinitis (itchy nose, sneezing, runny nose and blocked nose) and 2 questions for conjunctivitis (itchy/red eyes and watery eyes). Symptom scores (medication scores) each ranged from 0 to 3 (severe symptoms; highest medication category). The outcome of the overall combined symptom and medication score (CSMS) ranged from 0 (no symptoms and no medication) to 6 (severe symptoms and highest category of medication).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
arithmetic mean (standard deviation)	-0.31 ( 0.80 )	-0.45 ( 0.88 )

No statistical analyses for this end point

Secondary: 14_2_ANCOVA for change of rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

Top of page

End point title

14_2_ANCOVA for change of rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

End point description

Analysis of rhinitis score values. Symptom scores (medication scores) each ranged from 0 to 3 (severe symptoms; highest medication category). The outcome of the overall combined symptom and medication score (CSMS) ranged from 0 (no symptoms and no medication) to 6 (severe symptoms and highest category of medication).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
least squares mean (standard error)	-0.30 ( 0.07 )	-0.48 ( 0.05 )

ANCOVA for change of rhinitis CSMS

Statistical analysis description

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

332

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0147 ^[17]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

-0.04

Notes
[17] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 14_3_Rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Top of page

End point title

14_3_Rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

End point description

Analysis of rhinitis and conjunctivitis score values. Symptom scores (medication scores) each ranged from 0 to 3 (severe symptoms; highest medication category). The outcome of the overall combined symptom and medication score (CSMS) ranged from 0 (no symptoms and no medication) to 6 (severe symptoms and highest category of medication).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
arithmetic mean (standard deviation)	-0.28 ( 0.74 )	-0.40 ( 0.81 )

No statistical analyses for this end point

Secondary: 14_4_ANCOVA for change of rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

Top of page

End point title

14_4_ANCOVA for change of rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

End point description

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
least squares mean (standard error)	-0.28 ( 0.07 )	-0.45 ( 0.05 )

ANCOVA change of rhinitis and conjunctivitis CSMS

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

332

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0151 ^[18]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

-0.03

Notes
[18] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 14_5_Rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Top of page

End point title

14_5_Rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

End point description

Analysis of rhitis daily symptom score values. The rhinitis daily symptom score (rdSS) was calculated as the mean of the available rhinitis symptoms. The rdSS was calculated if at least 2 single rhinitis symptoms had been reported.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
arithmetic mean (standard deviation)	-0.10 ( 0.43 )	-0.25 ( 0.53 )

No statistical analyses for this end point

Secondary: 14_6_ANCOVA for change of rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

Top of page

End point title

14_6_ANCOVA for change of rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

End point description

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
least squares mean (standard error)	-0.12 ( 0.04 )	-0.24 ( 0.03 )

ANCOVA for change of rhinitis dSS

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

332

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0033 ^[19]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

-0.04

Notes
[19] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 14_7_Rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Top of page

End point title

14_7_Rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

End point description

Analysis of rhitis and conjunctivitis daily symptom score values. The overall daily symptoms score (dSS) were calculated as the mean symptom per day by summing up all available symptom scores and dividing by the number of the available symptoms. If less than 3 single symptoms were available, no dSS was to be calculated for the respective day.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
arithmetic mean (standard deviation)	-0.07 ( 0.35 )	-0.20 ( 0.44 )

No statistical analyses for this end point

Secondary: 14_8_ANCOVA for change of rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

Top of page

End point title

14_8_ANCOVA for change of rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

End point description

Analysis of rhitis and conjunctivitis daily symptom score values. The overall daily symptoms score (dSS) was calculated as the mean symptom per day by summing up all available symptom scores and dividing by the number of the available symptoms. If less than 3 single symptoms were available, no dSS was to be calculated for the respective day.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
least squares mean (standard error)	-0.09 ( 0.03 )	-0.21 ( 0.02 )

ANCOVA change of rhinitis and conjunctivitis dSS

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

332

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0016 ^[20]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

-0.04

Notes
[20] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 14_9_dMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Top of page

End point title

14_9_dMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

End point description

Rescue medication used for symptom control. The daily medication score (dMS) ranged from 0 (no medication taken) to 3 (corticosteroid tablets taken). Antihistamine tablets, eye drops, nasal drops or antihistamine sprays scored 1. Nasal corticoid spray scored 2. Corticoid tablets scored 3. If several questions for medications were answered with ‘yes’, the highest medication score category was to be taken. If more than one single category was missing or if all questions are not answered, the dMS was considered missing.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
median (standard deviation)	-0.21 ( 0.58 )	-0.20 ( 0.62 )

No statistical analyses for this end point

Secondary: 14_10_ANCOVA for change of dMS under the lowest daily ICS dose required to ensure asthma control at baseline

Top of page

End point title

14_10_ANCOVA for change of dMS under the lowest daily ICS dose required to ensure asthma control at baseline

End point description

Rescue medication used for symptom control. The daily medication score (dMS) ranged from 0 (no medication taken) to 3 (corticosteroid tablets taken). If several questions for medications were answered with ‘yes’, the highest medication score category was to be taken. If more than one single category was missing or if all questions are not answered, the dMS was considered missing.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	109	223
Units: Score
least squares mean (standard error)	-0.19 ( 0.05 )	-0.24 ( 0.04 )

ANCOVA for change of dMS

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

332

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3918 ^[21]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.06

Notes
[21] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 15_1_Specific IgG4 of D p [kU/L] - summary statistics

Top of page

End point title

15_1_Specific IgG4 of D p [kU/L] - summary statistics

End point description

Serum specific IgG4 to D p (in kU/L).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	124	262
Units: kU/L
arithmetic mean (standard deviation)	0.06 ( 0.60 )	4.70 ( 3.78 )

No statistical analyses for this end point

Secondary: 15_2_ANCOVA for change of specific IgG4 of D p [kU/L]

Top of page

End point title

15_2_ANCOVA for change of specific IgG4 of D p [kU/L]

End point description

Change in specific IgG4 to D p (in kU/L).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	124	262
Units: kU/L
least squares mean (standard error)	0.49 ( 0.30 )	5.05 ( 0.22 )

ANCOVA for change of specific IgG4 of D p [kU/L]

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

386

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[22]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

4.56

Confidence interval

level

95%

sides

2-sided

lower limit

3.93

upper limit

5.19

Notes
[22] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 15_3_Specific IgG4 of D f [KU/L] - summary statistics

Top of page

End point title

15_3_Specific IgG4 of D f [KU/L] - summary statistics

End point description

Serum specific IgG4 to D f (in kU/L).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	124	262
Units: KU/L
arithmetic mean (standard deviation)	0.03 ( 0.37 )	3.00 ( 2.95 )

No statistical analyses for this end point

Secondary: 15_4_ANCOVA for change of specific IgG4 of D f [KU/L]

Top of page

End point title

15_4_ANCOVA for change of specific IgG4 of D f [KU/L]

End point description

Change in specific IgG4 to D f (in kU/L).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	124	262
Units: KU/L
least squares mean (standard error)	0.27 ( 0.24 )	3.21 ( 0.18 )

ANCOVA for change of specific IgG4 of D f [KU/L]

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

386

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[23]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

2.94

Confidence interval

level

95%

sides

2-sided

lower limit

2.44

upper limit

3.44

Notes
[23] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 15_5_Eosinophils [10^9/L] - summary statistics

Top of page

End point title

15_5_Eosinophils [10^9/L] - summary statistics

End point description

Absolute eosinophil count.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	131	279
Units: 10^9/L
arithmetic mean (standard deviation)	-0.010 ( 0.181 )	0.001 ( 0.204 )

No statistical analyses for this end point

Secondary: 15_6_ANCOVA for change of eosinophils [10^9/L]

Top of page

End point title

15_6_ANCOVA for change of eosinophils [10^9/L]

End point description

Absolute eosinophil count.

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to baseline

End point values	Placebo	Acaroid
Number of subjects analysed	131	279
Units: 10^9/L
least squares mean (standard error)	-0.011 ( 0.017 )	0.008 ( 0.013 )

ANCOVA for change of eosinophils [10^9/L]

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

410

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3033 ^[24]

Method

ANCOVA

Parameter type

LS mean difference (net)

Point estimate

0.019

Confidence interval

level

95%

sides

2-sided

lower limit

-0.017

upper limit

0.054

Notes
[24] - Acaroid vs. placebo - ANCOVA analysis including treatment, pooled country, age group and baseline value

Secondary: 16_1_Time until the first moderate or severe asthma exacerbation during the diary phase after treatment

Top of page

End point title

16_1_Time until the first moderate or severe asthma exacerbation during the diary phase after treatment

End point description

Severe asthma exacerbation: One or more of the following criteria had to be fulfilled: use of systemic corticosteroids (tablets, suspension, or injection); increase from a stable maintenance dose of systemic corticosteroids for at least 3 days; hospitalization or emergency room visit due to the requirement of systemic corticosteroids for asthma treatment. Moderate asthma exacerbation: One or more of the following criteria had to be fulfilled: > 50% increase in SABA use and > 8 puffs per day on 2 of 3 consecutive days compared to baseline; ≥ 20% decrease in morning PEF from baseline on 2 of 3 consecutive days compared to baseline; Night time awakenings requiring SABA use on at least 2 of 3 consecutive nights.

End point type

Secondary

End point timeframe

Weeks after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Weeks
median (confidence interval 95%)	25.4 (13.4 to 25.4)	22.9 (17.1 to 22.9)

Time to event Kaplan Meier [weeks]

Statistical analysis description

Result of Kaplan-Meier did not give a valid parameter for CI. Median (confidence interval 95%): Placebo: 25.4 (13.4 to xx ) Acaroid: 22.9 (17.1 to xx). EudraCT reporting system doesn't allow to enter a missing value for 'xx'. The missing parameters were therefore replaced by exiting parameters: Placebo: 25.4 (13.4 to 25.4 ) Acaroid: 22.9 (17.1 to 22.9).

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[25]

P-value

= 0.9954 ^[26]

Method

Log-rank test

Confidence interval

Notes
[25] - Time-to-event analysis using Kaplan-Meier and log-rank test
[26] - Log-rank test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_2_Time until the first moderate or severe asthma exacerbation from the time of first injection until the end of trial

Top of page

End point title

16_2_Time until the first moderate or severe asthma exacerbation from the time of first injection until the end of trial

End point description

End point type

Secondary

End point timeframe

Weeks after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Weeks
median (confidence interval 95%)	34.0 (19.6 to 43.1)	36.9 (30.4 to 42.9)

Time to event Kaplan Meier [weeks]

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[27]

P-value

= 0.6535 ^[28]

Method

Log-rank test

Confidence interval

Notes
[27] - Time-to-event analysis using Kaplan-Meier and log-rank test
[28] - Log-rank test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_3_Time until the first moderate or severe asthma exacerbation with the minimal ICS dose assessed after treatment

Top of page

End point title

16_3_Time until the first moderate or severe asthma exacerbation with the minimal ICS dose assessed after treatment

End point description

End point type

Secondary

End point timeframe

Weeks after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Weeks
median (confidence interval 95%)	22.0 (22.0 to 22.0)	20.9 (20.9 to 20.9)

Time to event Kaplan Meier [weeks]

Statistical analysis description

Result of Kaplan-Meier did not give a valid parameter for CI. Median (confidence interval 95%): Placebo: xx (22.0 to xx ) Acaroid: xx (20.9 to xx). EudraCT reporting system doesn't allow to enter a missing value for 'xx'. The missing parameters were therefore replaced by exiting parameters: Placebo: 22.0 (22.0 to 22.0 ) Acaroid: 20.9 (20.9 to 20.9).

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

384

Analysis specification

Pre-specified

Analysis type

other ^[29]

P-value

= 0.6964 ^[30]

Method

Log-rank test

Confidence interval

Notes
[29] - Time-to-event analysis using Kaplan-Meier and log-rank test
[30] - Log-rank test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_4_Number of asthma exacerbations (moderate or severe) during the diary phase after treatment - summary statistics

Top of page

End point title

16_4_Number of asthma exacerbations (moderate or severe) during the diary phase after treatment - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number
arithmetic mean (standard deviation)	1.4 ( 2.0 )	1.2 ( 1.7 )

Number of asthma moderate or severe exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[31]

P-value

= 0.5572 ^[32]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[31] - Descriptive statistics
[32] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_5_Number of asthma exacerbations (moderate or severe) during the diary phase after treatment

Top of page

End point title

16_5_Number of asthma exacerbations (moderate or severe) during the diary phase after treatment

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number of exacerbation
'0'	69	141
'1'	23	64
'2'	13	28
'3'	7	21
'4'	6	9
'5'	4	14
'6'	6	4
'7'	3	3
'8'	1	1
'9'	0	1

No statistical analyses for this end point

Secondary: 16_6_Number of asthma exacerbations (moderate or severe) from the time of first injection until the end of trial - summary statistics

Top of page

End point title

16_6_Number of asthma exacerbations (moderate or severe) from the time of first injection until the end of trial - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number
arithmetic mean (standard deviation)	2.9 ( 3.8 )	2.4 ( 3.2 )

Number of moderate or severe asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[33]

P-value

= 0.8345 ^[34]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[33] - Descriptive statistics
[34] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_7_Number of asthma exacerbations (moderate or severe) from the time of first injection until the end of trial

Top of page

End point title

16_7_Number of asthma exacerbations (moderate or severe) from the time of first injection until the end of trial

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number of exacerbation
'0'	47	98
'1'	25	66
'2'	9	27
'3'	12	23
'4'	7	20
'5'	4	9
'6'	8	9
'7'	4	7
'8'	4	7
'9'	2	5
'10'	3	6
'11'	1	3
'12'	1	1
'13'	0	0
'14'	1	4
'15'	3	1
'16'	0	0
'17'	1	0

No statistical analyses for this end point

Secondary: 16_8_Number of asthma exacerbations (moderate or severe) with the minimal ICS dose assessed after treatment - summary statistics

Top of page

End point title

16_8_Number of asthma exacerbations (moderate or severe) with the minimal ICS dose assessed after treatment - summary statistics

End point description

Number of moderate or severe asthma exacerbations with the minmal ICS dose after treatment

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Number
arithmetic mean (standard deviation)	0.9 ( 1.6 )	0.7 ( 1.2 )

Number of moderate or severe asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

384

Analysis specification

Pre-specified

Analysis type

other ^[35]

P-value

= 0.7037 ^[36]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[35] - Descriptive statistics
[36] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_9_Number of asthma exacerbations (moderate or severe) with the minimal ICS dose assessed after treatment

Top of page

End point title

16_9_Number of asthma exacerbations (moderate or severe) with the minimal ICS dose assessed after treatment

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Number of exacerbation
'0'	77	167
'1'	18	51
'2'	11	18
'3'	9	13
'4'	1	8
'5'	1	2
'6'	3	2
'7'	2	1

No statistical analyses for this end point

Secondary: 16_10_Number of severe asthma exacerbations during the diary phase after treatment - summary statistics

Top of page

End point title

16_10_Number of severe asthma exacerbations during the diary phase after treatment - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number
arithmetic mean (standard deviation)	0.0 ( 0.1 )	0.0 ( 0.1 )

Number of severe asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[37]

P-value

= 0.7142 ^[38]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[37] - Descriptive statistics
[38] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_11_Number of severe asthma exacerbations during the diary phase after treatment

Top of page

End point title

16_11_Number of severe asthma exacerbations during the diary phase after treatment

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number of exacerbation
'0'	131	285
'1'	1	1

No statistical analyses for this end point

Secondary: 16_12_Number of severe asthma exacerbations from the time of first injection until the end of trial - summary statistics

Top of page

End point title

16_12_Number of severe asthma exacerbations from the time of first injection until the end of trial - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number
arithmetic mean (standard deviation)	0.0 ( 0.1 )	0.0 ( 0.1 )

Number of severe asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[39]

P-value

= 0.7893 ^[40]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[39] - Descriptive statistics
[40] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_13_Number of severe asthma exacerbations from the time of first injection until the end of trial

Top of page

End point title

16_13_Number of severe asthma exacerbations from the time of first injection until the end of trial

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number of exacerbation
'0'	130	284
'1'	2	2

No statistical analyses for this end point

Secondary: 16_14_Number of severe asthma exacerbations with the minimal ICS dose assessed after treatment - summary statistics

Top of page

End point title

16_14_Number of severe asthma exacerbations with the minimal ICS dose assessed after treatment - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Number
arithmetic mean (standard deviation)	0.0 ( 0.0 )	0.0 ( 0.0 )

Number of severe asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

384

Analysis specification

Pre-specified

Analysis type

other ^[41]

P-value

= 0.5 ^[42]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[41] - Descriptive statistics
[42] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_15_Number of severe asthma exacerbations with the minimal ICS dose assessed after treatment

Top of page

End point title

16_15_Number of severe asthma exacerbations with the minimal ICS dose assessed after treatment

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Number of exacerbation
'0'	122	262

No statistical analyses for this end point

Secondary: 16_16_Number of moderate asthma exacerbations during the diary phase after treatment - summary statistics

Top of page

End point title

16_16_Number of moderate asthma exacerbations during the diary phase after treatment - summary statistics

End point description

Moderate asthma exacerbation: One or more of the following criteria had to be fulfilled: > 50% increase in SABA use and > 8 puffs per day on 2 of 3 consecutive days compared to baseline; ≥ 20% decrease in morning PEF from baseline on 2 of 3 consecutive days compared to baseline; Night time awakenings requiring SABA use on at least 2 of 3 consecutive nights.

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number
arithmetic mean (standard deviation)	1.3 ( 2.0 )	1.2 ( 1.7 )

Number of moderate asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[43]

P-value

= 0.5398 ^[44]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[43] - Descriptive statistics
[44] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_17_Number of moderate asthma exacerbations during the diary phase after treatment

Top of page

End point title

16_17_Number of moderate asthma exacerbations during the diary phase after treatment

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number of exacerbation
'0'	70	141
'1'	22	65
'2'	13	27
'3'	7	21
'4'	6	9
'5'	4	14
'6'	6	4
'7'	3	3
'8'	1	1
'9'	0	1

No statistical analyses for this end point

Secondary: 16_18_Number of moderate asthma exacerbations from the time of first injection until the end of trial - summary statistics

Top of page

End point title

16_18_Number of moderate asthma exacerbations from the time of first injection until the end of trial - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number
arithmetic mean (standard deviation)	2.9 ( 3.8 )	2.4 ( 3.2 )

Number of moderate asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

other ^[45]

P-value

= 0.8301 ^[46]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[45] - Descriptive statistics
[46] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_19_Number of moderate asthma exacerbations from the time of first injection until the end of trial

Top of page

End point title

16_19_Number of moderate asthma exacerbations from the time of first injection until the end of trial

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	132	286
Units: Number of exacerbation
'0'	47	98
'1'	26	67
'2'	8	26
'3'	12	23
'4'	7	20
'5'	5	9
'6'	7	9
'7'	4	7
'8'	4	8
'9'	2	4
'10'	3	6
'11'	1	3
'12'	1	1
'13'	0	0
'14'	1	4
'15'	3	1
'16'	0	0
'17'	1	0

No statistical analyses for this end point

Secondary: 16_20_Number of moderate asthma exacerbations with the minimal ICS dose assessed after treatment - summary statistics

Top of page

End point title

16_20_Number of moderate asthma exacerbations with the minimal ICS dose assessed after treatment - summary statistics

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Number
arithmetic mean (standard deviation)	0.9 ( 1.6 )	0.7 ( 1.2 )

Number of moderate asthma exacerbations

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

384

Analysis specification

Pre-specified

Analysis type

other ^[47]

P-value

= 0.7037 ^[48]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[47] - Descriptive statistics
[48] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Secondary: 16_21_Number of moderate asthma exacerbations with the minimal ICS dose assessed after treatment

Top of page

End point title

16_21_Number of moderate asthma exacerbations with the minimal ICS dose assessed after treatment

End point description

End point type

Secondary

End point timeframe

Number of asthma exacerbations after Allergen Immunotherapy categorized

End point values	Placebo	Acaroid
Number of subjects analysed	122	262
Units: Number of exacerbation
'0'	77	167
'1'	18	51
'2'	11	18
'3'	9	13
'4'	1	8
'5'	1	2
'6'	3	2
'7'	2	1

No statistical analyses for this end point

Secondary: 17_1_Clinical chemistry: Creatinine [μmol/L]: absolute values and change

Top of page

End point title

17_1_Clinical chemistry: Creatinine [μmol/L]: absolute values and change

End point description

Creatinine [μmol/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[49]	290 ^[50]
Units: μmol/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	4.00 ( 12.52 )	4.14 ( 11.42 )
Last treatment visit - Baseline (T1)	4.31 ( 8.19 )	4.40 ( 8.20 )

Notes
[49] - Safety Set
[50] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[51]

P-value

= 0.983 ^[52]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[51] - Descriptive statistics
[52] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[53]

P-value

= 0.937 ^[54]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[53] - Descriptive statistics
[54] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 17_2_Clinical chemistry: Bilirubin, total [μmol/L]: absolute values and change

Top of page

End point title

17_2_Clinical chemistry: Bilirubin, total [μmol/L]: absolute values and change

End point description

Bilirubin, total [μmol/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[55]	290 ^[56]
Units: μmol/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	-1.80 ( 6.21 )	-1.44 ( 5.23 )
Last treatment visit - Baseline (T1)	0.46 ( 5.12 )	-0.50 ( 4.57 )

Notes
[55] - Safety Set
[56] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[57]

P-value

= 0.6087 ^[58]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[57] - Descriptive statistics
[58] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[59]

P-value

= 0.0207 ^[60]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[59] - Descriptive statistics
[60] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 17_3_Clinical chemistry: ASAT (Aspartate Aminotransferase) [U/L]: absolute values and change

Top of page

End point title

17_3_Clinical chemistry: ASAT (Aspartate Aminotransferase) [U/L]: absolute values and change

End point description

ASAT (Aspartate Aminotransferase) [U/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[61]	290 ^[62]
Units: U/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	2.90 ( 11.14 )	2.96 ( 8.00 )
Last treatment visit - Baseline (T1)	7.16 ( 8.94 )	5.33 ( 21.38 )

Notes
[61] - Safety Set
[62] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[63]

P-value

= 0.7378 ^[64]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[63] - Descriptive statistics
[64] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[65]

P-value

= 0.4345 ^[66]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[65] - Descriptive statistics
[66] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 17_4_Clinical chemistry: ALAT (Alanine Aminotransferase) [U/L]: absolute values and change

Top of page

End point title

17_4_Clinical chemistry: ALAT (Alanine Aminotransferase) [U/L]: absolute values and change

End point description

ALAT (Alanine Aminotransferase) [U/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[67]	290 ^[68]
Units: U/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	2.82 ( 13.53 )	5.62 ( 14.52 )
Last treatment visit - Baseline (T1)	3.12 ( 13.42 )	-1.81 ( 21.94 )

Notes
[67] - Safety Set
[68] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[69]

P-value

= 0.0067 ^[70]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[69] - Descriptive statistics
[70] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[71]

P-value

= 0.0138 ^[72]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[71] - Descriptive statistics
[72] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 17_5_Clinical chemistry: γ-GT (Gamma Glutamyl Transferase) [U/L]: absolute values and change

Top of page

End point title

17_5_Clinical chemistry: γ-GT (Gamma Glutamyl Transferase) [U/L]: absolute values and change

End point description

γ-GT (Gamma Glutamyl Transferase) [U/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[73]	290 ^[74]
Units: U/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.08 ( 16.95 )	-0.08 ( 10.82 )
Last treatment visit - Baseline (T1)	0.46 ( 14.84 )	0.00 ( 9.57 )

Notes
[73] - Safety Set
[74] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[75]

P-value

= 0.3629 ^[76]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[75] - Descriptive statistics
[76] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[77]

P-value

= 0.0742 ^[78]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[77] - Descriptive statistics
[78] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 17_6_Clinical chemistry: Glucose [mmol/L]: absolute values and change

Top of page

End point title

17_6_Clinical chemistry: Glucose [mmol/L]: absolute values and change

End point description

Glucose [mmol/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[79]	290 ^[80]
Units: mmol/L]
arithmetic mean (standard deviation)
Final visit – Screening (S1)	-0.17 ( 0.78 )	-0.10 ( 0.83 )
Last treatment visit - Baseline (T1)	-0.35 ( 0.79 )	-0.19 ( 0.93 )

Notes
[79] - Safety Set
[80] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[81]

P-value

= 0.5011 ^[82]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[81] - Descriptive statistics
[82] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[83]

P-value

= 0.1691 ^[84]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[83] - Descriptive statistics
[84] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_1_Hematology: Hemoglobin [mmol/L]: absolute values and change

Top of page

End point title

18_1_Hematology: Hemoglobin [mmol/L]: absolute values and change

End point description

Hemoglobin [mmol/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[85]	290 ^[86]
Units: mmol/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	-0.01 ( 0.53 )	0.02 ( 0.56 )
Last treatment visit - Baseline (T1)	-0.08 ( 0.52 )	-0.11 ( 0.44 )

Notes
[85] - Safety Set
[86] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[87]

P-value

= 0.762 ^[88]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[87] - Descriptive statistics
[88] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[89]

P-value

= 0.4341 ^[90]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[89] - Descriptive statistics
[90] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_2_Hematology: Leukocytes [10^9/L]: absolute values and change

Top of page

End point title

18_2_Hematology: Leukocytes [10^9/L]: absolute values and change

End point description

Leukocytes [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[91]	290 ^[92]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.39 ( 1.90 )	0.43 ( 1.86 )
Last treatment visit - Baseline (T1)	0.13 ( 1.63 )	0.06 ( 1.76 )

Notes
[91] - Safety Set
[92] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[93]

P-value

= 0.6216 ^[94]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[93] - Descriptive statistics
[94] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[95]

P-value

= 0.8715 ^[96]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[95] - Descriptive statistics
[96] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_3_Hematology: Basophils [10^9/L]: absolute values and change

Top of page

End point title

18_3_Hematology: Basophils [10^9/L]: absolute values and change

End point description

Basophils [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[97]	290 ^[98]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.03 ( 0.06 )	0.03 ( 0.05 )
Last treatment visit - Baseline (T1)	0.01 ( 0.04 )	0.00 ( 0.04 )

Notes
[97] - Safety Set
[98] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[99]

P-value

= 0.6571 ^[100]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[99] - Descriptive statistics
[100] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[101]

P-value

= 0.1964 ^[102]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[101] - Descriptive statistics
[102] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_4_Hematology: Basophils/Leukocytes [%]: absolute values and change

Top of page

End point title

18_4_Hematology: Basophils/Leukocytes [%]: absolute values and change

End point description

Basophils/Leukocytes [%]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[103]	290 ^[104]
Units: [%]
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.31 ( 0.59 )	0.28 ( 0.35 )
Last treatment visit - Baseline (T1)	0.11 ( 0.22 )	0.07 ( 0.32 )

Notes
[103] - Safety Set
[104] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[105]

P-value

= 0.7356 ^[106]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[105] - Descriptive statistics
[106] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[107]

P-value

= 0.1312 ^[108]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[107] - Descriptive statistics
[108] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_5_Hematology: Eosinophils [10^9/L]: absolute values and change

Top of page

End point title

18_5_Hematology: Eosinophils [10^9/L]: absolute values and change

End point description

Eosinophils [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[109]	290 ^[110]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	-0.04 ( 0.22 )	-0.05 ( 0.27 )
Last treatment visit - Baseline (T1)	0.01 ( 0.20 )	-0.01 ( 0.18 )

Notes
[109] - Safety Set
[110] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[111]

P-value

= 0.7385 ^[112]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[111] - Descriptive statistics
[112] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[113]

P-value

= 0.29 ^[114]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[113] - Descriptive statistics
[114] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_6_Hematology: Eosinophils/Leukocytes [%]: absolute values and change

Top of page

End point title

18_6_Hematology: Eosinophils/Leukocytes [%]: absolute values and change

End point description

Eosinophils/Leukocytes [%]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[115]	290 ^[116]
Units: [%]
arithmetic mean (standard deviation)
Final visit – Screening (S1)	-0.95 ( 3.26 )	-0.97 ( 3.61 )
Last treatment visit - Baseline (T1)	0.18 ( 2.62 )	-0.29 ( 2.87 )

Notes
[115] - Safety Set
[116] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[117]

P-value

= 0.7898 ^[118]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[117] - Descriptive statistics
[118] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[119]

P-value

= 0.1483 ^[120]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[119] - Descriptive statistics
[120] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_7_Hematology: Lymphocytes [10^9/L]: absolute values and change

Top of page

End point title

18_7_Hematology: Lymphocytes [10^9/L]: absolute values and change

End point description

Lymphocytes [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[121]	290 ^[122]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.10 ( 0.56 )	0.14 ( 0.60 )
Last treatment visit - Baseline (T1)	-0.06 ( 0.62 )	-0.03 ( 0.54 )

Notes
[121] - Safety Set
[122] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Acaroid v Placebo

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[123]

P-value

= 0.4392 ^[124]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[123] - Descriptive statistics
[124] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[125]

P-value

= 0.3844 ^[126]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[125] - Descriptive statistics
[126] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_8_Hematology: Lymphocytes/Leukocytes [%]: absolute values and change

Top of page

End point title

18_8_Hematology: Lymphocytes/Leukocytes [%]: absolute values and change

End point description

Lymphocytes/Leukocytes [%]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[127]	290 ^[128]
Units: [%]
arithmetic mean (standard deviation)
Final visit – Screening (S1)	-0.67 ( 9.47 )	0.43 ( 7.50 )
Last treatment visit - Baseline (T1)	-1.54 ( 8.38 )	-0.55 ( 7.45 )

Notes
[127] - Safety Set
[128] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[129]

P-value

= 0.1111 ^[130]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[129] - Descriptive statistics
[130] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[131]

P-value

= 0.2056 ^[132]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[131] - Descriptive statistics
[132] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_9_Hematology: Monocytes [10^9/L]: absolute values and change

Top of page

End point title

18_9_Hematology: Monocytes [10^9/L]: absolute values and change

End point description

Monocytes [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[133]	290 ^[134]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.05 ( 0.21 )	0.05 ( 0.16 )
Last treatment visit - Baseline (T1)	-0.03 ( 0.15 )	-0.05 ( 0.17 )

Notes
[133] - Safety Set
[134] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[135]

P-value

= 0.9355 ^[136]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[135] - Descriptive statistics
[136] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[137]

P-value

= 0.286 ^[138]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[137] - Descriptive statistics
[138] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_10_Hematology: Monocytes/Leukocytes [%]: absolute values and change

Top of page

End point title

18_10_Hematology: Monocytes/Leukocytes [%]: absolute values and change

End point description

Monocytes/Leukocytes [%]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[139]	290 ^[140]
Units: [%]
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.37 ( 2.47 )	0.27 ( 2.19 )
Last treatment visit - Baseline (T1)	-0.69 ( 1.92 )	-0.73 ( 2.16 )

Notes
[139] - Safety Set
[140] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[141]

P-value

= 0.8945 ^[142]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[141] - Descriptive statistics
[142] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[143]

P-value

= 0.6391 ^[144]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[143] - Descriptive statistics
[144] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_11_Hematology: Neutrophils [10^9/L]: absolute values and change

Top of page

End point title

18_11_Hematology: Neutrophils [10^9/L]: absolute values and change

End point description

Neutrophils [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[145]	290 ^[146]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.26 ( 1.77 )	0.26 ( 1.53 )
Last treatment visit - Baseline (T1)	0.23 ( 1.40 )	0.11 ( 1.49 )

Notes
[145] - Safety Set
[146] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[147]

P-value

= 0.5462 ^[148]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[147] - Descriptive statistics
[148] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[149]

P-value

= 0.7094 ^[150]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[149] - Descriptive statistics
[150] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_12_Hematology: Neutrophils/Leukocytes [%]: absolute values and change

Top of page

End point title

18_12_Hematology: Neutrophils/Leukocytes [%]: absolute values and change

End point description

Neutrophils/Leukocytes [%]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[151]	290 ^[152]
Units: [%]
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.88 ( 11.44 )	-0.10 ( 9.54 )
Last treatment visit - Baseline (T1)	1.93 ( 9.46 )	1.76 ( 9.81 )

Notes
[151] - Safety Set
[152] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[153]

P-value

= 0.2342 ^[154]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[153] - Descriptive statistics
[154] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Acaroid v Placebo

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[155]

P-value

= 0.6848 ^[156]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[155] - Descriptive statistics
[156] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 18_13_Hematology: Platelets [10^9/L]: absolute values and change

Top of page

End point title

18_13_Hematology: Platelets [10^9/L]: absolute values and change

End point description

Platelets [10^9/L]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[157]	290 ^[158]
Units: 10^9/L
arithmetic mean (standard deviation)
Final visit – Screening (S1)	6.05 ( 41.16 )	10.26 ( 47.72 )
Last treatment visit - Baseline (T1)	11.06 ( 41.31 )	4.34 ( 40.58 )

Notes
[157] - Safety Set
[158] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[159]

P-value

= 0.319 ^[160]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[159] - Descriptive statistics
[160] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[161]

P-value

= 0.1039 ^[162]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[161] - Descriptive statistics
[162] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 19_Urinalysis

Top of page

End point title

19_Urinalysis

End point description

The absolute and relative numbers of patients with urinalysis parameter values at normal or abnormal range (clinically significant or not) are displayed. At the last treatment visit, no patients were reported with abnormal clinically significant values for any urinalysis parameter. At the final visit, patients with abnormal clinically significant values were identified for urine occult blood (placebo: 1 patient [0.7%]; Acaroid: 0 patients) and urine glucose (placebo: 0 patients; Acaroid: 1 patient [0.3%]).

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[163]	290 ^[164]
Units: Number
1a_Blood: S1: Normal	134	288
1a_Blood: S1: Abnormal NCS	0	2
1a_Blood: S1: Abnormal CS	0	0
1b_Blood: FV: Normal	132	279
1b_Blood: FV: Abnormal NCS	0	4
1b_Blood: FV: Abnormal CS	1	0
2a_Glucose: S1: Normal	134	290
2a_Glucose: S1: Abnormal NCS	0	0
2a_Glucose: S1: Abnormal CS	0	0
2b_Glucose: FV: Normal	133	282
2b_Glucose: FV: Abnormal NCS	0	0
2b_Glucose: FV: Abnormal CS	0	1

Notes
[163] - Safety Set
[164] - Safety Set

No statistical analyses for this end point

Secondary: 20_1_Vital signs: Systolic blood pressure [mmHg]

Top of page

End point title

20_1_Vital signs: Systolic blood pressure [mmHg]

End point description

Systolic blood pressure [mmHg]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[165]	290 ^[166]
Units: mmHg
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.7 ( 9.3 )	0.4 ( 9.9 )
Last treatment visit - Baseline (T1)	-0.3 ( 9.6 )	-0.6 ( 9.6 )

Notes
[165] - Safety Set
[166] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[167]

P-value

= 0.4265 ^[168]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[167] - Descriptive statistics
[168] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[169]

P-value

= 0.6831 ^[170]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[169] - Descriptive statistics
[170] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 20_2_Vital signs: Diastolic blood pressure [mmHg]

Top of page

End point title

20_2_Vital signs: Diastolic blood pressure [mmHg]

End point description

Diastolic blood pressure [mmHg]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[171]	290 ^[172]
Units: mmHg
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.4 ( 7.5 )	0.2 ( 7.9 )
Last treatment visit - Baseline (T1)	0.5 ( 7.6 )	0.2 ( 7.7 )

Notes
[171] - Safety Set
[172] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[173]

P-value

= 0.7274 ^[174]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[173] - Descriptive statistics
[174] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[175]

P-value

= 0.7094 ^[176]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[175] - Descriptive statistics
[176] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 20_3_Vital signs: Heart rate [beats/min]

Top of page

End point title

20_3_Vital signs: Heart rate [beats/min]

End point description

Heart rate [beats/min]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[177]	290 ^[178]
Units: beats/min
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.3 ( 8.4 )	0.4 ( 8.3 )
Last treatment visit - Baseline (T1)	-0.7 ( 7.2 )	-0.1 ( 7.4 )

Notes
[177] - Safety Set
[178] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[179]

P-value

= 0.5775 ^[180]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[179] - Descriptive statistics
[180] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[181]

P-value

= 0.4971 ^[182]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[181] - Descriptive statistics
[182] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 20_4_Vital signs: Respiratory rate [breaths/min]

Top of page

End point title

20_4_Vital signs: Respiratory rate [breaths/min]

End point description

Respiratory rate [breaths/min]

End point type

Secondary

End point timeframe

Change after Allergen Immunotherapy to screening (S1) / to baseline (T1)

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[183]	290 ^[184]
Units: breaths/min
arithmetic mean (standard deviation)
Final visit – Screening (S1)	0.0 ( 1.6 )	-0.1 ( 1.6 )
Last treatment visit - Baseline (T1)	0.1 ( 1.5 )	0.0 ( 1.4 )

Notes
[183] - Safety Set
[184] - Safety Set

Change final visit to screening visit (S1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[185]

P-value

= 0.3422 ^[186]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[185] - Descriptive statistics
[186] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Change last treatment visit to baseline visit (T1)

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[187]

P-value

= 0.9453 ^[188]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[187] - Descriptive statistics
[188] - Two-sided Mann-Whitney U-test comparing the active treatment group vs. placebo

Secondary: 21_Tolerability assessments of investigator and patient

Top of page

End point title

21_Tolerability assessments of investigator and patient

End point description

Assessment of the overall tolerability by the investigator and the patient using a 5 point Likert scale (1=very bad; 5=very good)

End point type

Secondary

End point timeframe

At trial termination

End point values	Placebo	Acaroid
Number of subjects analysed	134 ^[189]	290 ^[190]
Units: Scale
arithmetic mean (standard deviation)
Investigator's assessment	4.5 ( 0.7 )	4.4 ( 0.8 )
Patient's assessment	4.5 ( 0.7 )	4.3 ( 0.8 )

Notes
[189] - Safety set
[190] - Safety set

Tolerability assessments of investigator

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[191]

P-value

= 0.9753 ^[192]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[191] - Descriptive statistics
[192] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Tolerability assessments of patient

Comparison groups

Placebo v Acaroid

Number of subjects included in analysis

424

Analysis specification

Pre-specified

Analysis type

other ^[193]

P-value

= 0.9987 ^[194]

Method

Wilcoxon (Mann-Whitney)

Confidence interval

Notes
[193] - Descriptive statistics
[194] - One-sided Mann-Whitney U-test stratified by pooled country and age group comparing active vs. placebo

Adverse events

Top of page

Timeframe for reporting adverse events

Serious adverse events occuring from the first screening visit (including trial-related procedures) until 30 days after final visit. Non-serious adverse events are presented in the Safety Set (SAF) from the onset of treatment to 30 d after final visit.

Adverse event reporting additional description

SAEs were reported with similar frequency on active and placebo treatment (placebo: 5 events in 5 patients [3.7%]; Acaroid: 11 events in 8 patients [2.8%]. One SAE in 1 patient in the active treatment group (0.3%; none with placebo) was assessed as related to IMP (active treatment, hypersensitivity systemic adverse event).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Placebo

Reporting group description

One patient 0904-032 was not included in the analysis of SAEs because the patient withdrew from study before treatment started. The patient did not have an adverse event / SAE.

Reporting group title

Acaroid

Reporting group description

One patient 0908-004 was not included in the analysis of SAEs because the patient withdrew from study before treatment started. The patient did not have an adverse event / SAE.

Serious adverse events	Placebo	Acaroid
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 134 (3.73%)	8 / 290 (2.76%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Lip injury
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 134 (0.75%)	0 / 290 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Foetal death
subjects affected / exposed	1 / 134 (0.75%)	0 / 290 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
High risk pregnancy
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	1 / 134 (0.75%)	0 / 290 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 134 (0.75%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis allergic
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 134 (0.75%)	0 / 290 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear infection
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Parvovirus infection
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Type 1 diabetes mellitus
subjects affected / exposed	0 / 134 (0.00%)	1 / 290 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Acaroid
Total subjects affected by non serious adverse events
subjects affected / exposed	72 / 134 (53.73%)	214 / 290 (73.79%)
Nervous system disorders
Headache
subjects affected / exposed	7 / 134 (5.22%)	10 / 290 (3.45%)
occurrences all number	13	16
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	15 / 134 (11.19%)	124 / 290 (42.76%)
occurrences all number	37	628
Injection site pain
subjects affected / exposed	1 / 134 (0.75%)	16 / 290 (5.52%)
occurrences all number	1	33
Injection site pruritus
subjects affected / exposed	3 / 134 (2.24%)	36 / 290 (12.41%)
occurrences all number	9	113
Injection site swelling
subjects affected / exposed	4 / 134 (2.99%)	133 / 290 (45.86%)
occurrences all number	6	586
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	14 / 134 (10.45%)	36 / 290 (12.41%)
occurrences all number	16	44
Infections and infestations
Bronchitis
subjects affected / exposed	3 / 134 (2.24%)	15 / 290 (5.17%)
occurrences all number	3	16
Pharyngitis
subjects affected / exposed	13 / 134 (9.70%)	15 / 290 (5.17%)
occurrences all number	17	23
Viral upper respiratory tract infection
subjects affected / exposed	20 / 134 (14.93%)	48 / 290 (16.55%)
occurrences all number	26	76

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

29 Nov 2017

The initial Trial Protocol final 1.0, dated 03 Aug 2016, was amended twice after the enrolment of patients (first patient, first screening was on 22 Mar 2017), leading to final Trial Protocol 2.0, dated 04 Aug 2017, and to final Trial Protocol 3.0, dated 29 Nov 2017.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1_Change of minimal controlled dose (multiple imputation)

Primary: 1_Change of minimal controlled dose (multiple imputation)

Secondary: 2_1_Minimal controlled dose [μg] – summary statistics

Secondary: 2_1_Minimal controlled dose [μg] – summary statistics

Secondary: 2_2_Change of minimal controlled ICS dose [μg]

Secondary: 2_2_Change of minimal controlled ICS dose [μg]

Secondary: 3_1_ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 3_1_ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 3_2_ANCOVA for change of ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline

Secondary: 3_2_ANCOVA for change of ACQ6 score under the highest daily ICS dose the patient was not controlled at baseline

Secondary: 3_3_Categorical display of mean ACQ6 score under the lowest daily ICS dose the patient was controlled at post-treatment

Secondary: 3_3_Categorical display of mean ACQ6 score under the lowest daily ICS dose the patient was controlled at post-treatment

Secondary: 4_1_Night time awakening with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 4_1_Night time awakening with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 4_2_ANCOVA for change of night time awakening with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 4_2_ANCOVA for change of night time awakening with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 5_1_Severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline – summary statistics

Secondary: 5_1_Severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline – summary statistics

Secondary: 5_2_ANCOVA for change of severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 5_2_ANCOVA for change of severity of asthma symptoms with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 6_1_Limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 6_1_Limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 6_2_ANCOVA for change of limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 6_2_ANCOVA for change of limitation of daily activities with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 7_1_Shortness of breath with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 7_1_Shortness of breath with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 7_2_ANCOVA for change of shortness of breath with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 7_2_ANCOVA for change of shortness of breath with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 8_1_Wheezing with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 8_1_Wheezing with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 8_2_ANCOVA for change of wheezing with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 8_2_ANCOVA for change of wheezing with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 9_1_Number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline - summary statistics

Secondary: 9_1_Number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline - summary statistics

Secondary: 9_2_ANCOVA for change of number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline

Secondary: 9_2_ANCOVA for change of number of inhalations of bronchodilator rescue medication with the daily ICS highest dose the patient was not controlled at baseline

Secondary: 10_1_Outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 10_1_Outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 10_2_ANCOVA for change of outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 10_2_ANCOVA for change of outcome of Mini-AQLQ with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 11_1_Mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline - summary statistcs

Secondary: 11_1_Mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline - summary statistcs

Secondary: 11_2_ANCOVA for change of mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 11_2_ANCOVA for change of mean pre-bronchodilator morning peak flow [L/min] with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 12_1_Patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline - summary statistics

Secondary: 12_1_Patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline - summary statistics

Secondary: 12_2_ANCOVA for change of patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline

Secondary: 12_2_ANCOVA for change of patient's mean FEV1 [L/s] value with the highest daily dose ICS the patient was not controlled at baseline

Secondary: 13_1_Relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 13_1_Relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline - summary statistics

Secondary: 13_2_ANCOVA for change in relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 13_2_ANCOVA for change in relative number of symptom free days with the highest daily ICS dose the patient was not controlled at baseline

Secondary: 14_1_Rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_1_Rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_2_ANCOVA for change of rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_2_ANCOVA for change of rhinitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_3_Rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_3_Rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_4_ANCOVA for change of rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_4_ANCOVA for change of rhinitis and conjunctivitis CSMS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_5_Rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_5_Rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_6_ANCOVA for change of rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_6_ANCOVA for change of rhinitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_7_Rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_7_Rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_8_ANCOVA for change of rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_8_ANCOVA for change of rhinitis and conjunctivitis dSS under the lowest daily ICS dose required to ensure asthma control at baseline

Secondary: 14_9_dMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_9_dMS under the lowest daily ICS dose required to ensure asthma control at baseline - summary statistics

Secondary: 14_10_ANCOVA for change of dMS under the lowest daily ICS dose required to ensure asthma control at baseline