Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43871 clinical trials with a EudraCT protocol, of which 7290 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

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

< Back to search results

Clinical Trial Results:
A multi-center, randomized, double-blind, active and placebo-controlled study to investigate the safety and efficacy of ligelizumab (QGE031) in the treatment of Chronic Spontaneous Urticaria (CSU) in adolescents and adults inadequately controlled with H1-antihistamines

Summary
EudraCT number	2018-000839-28
Trial protocol	FR HU DK ES DE SE AT GR CZ BG PL HR
Global end of trial date	14 Jun 2022

Results information
Results version number	v1(current)
This version publication date	29 Dec 2022
First version publication date	29 Dec 2022
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

CQGE031C2302

ISRCTN number

-

US NCT number

NCT03580369

WHO universal trial number (UTN)

-

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com

Scientific contact

Study Director, Novartis Pharmaceuticals, 1 (862) 778-8300, novartis.email@novartis.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001811-PIP02-15

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

No

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

Yes

Analysis stage

Final

Date of interim/final analysis

14 Jun 2022

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

14 Jun 2022

Was the trial ended prematurely?

No

Main objective of the trial

The main purpose of this trial was to demonstrate that ligelizumab (72 mg q4w and/or 120 mg q4w) is superior to placebo and superior to omalizumab 300 mg q4w measured by change from baseline in UAS7 at Week 12

Protection of trial subjects

This study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

17 Oct 2018

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 53

Country: Number of subjects enrolled

Austria: 10

Country: Number of subjects enrolled

Brazil: 28

Country: Number of subjects enrolled

Bulgaria: 27

Country: Number of subjects enrolled

Canada: 39

Country: Number of subjects enrolled

Colombia: 13

Country: Number of subjects enrolled

Croatia: 5

Country: Number of subjects enrolled

Czechia: 31

Country: Number of subjects enrolled

Denmark: 10

Country: Number of subjects enrolled

France: 22

Country: Number of subjects enrolled

Germany: 118

Country: Number of subjects enrolled

Greece: 28

Country: Number of subjects enrolled

Guatemala: 12

Country: Number of subjects enrolled

Hungary: 18

Country: Number of subjects enrolled

India: 42

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 99

Country: Number of subjects enrolled

Malaysia: 23

Country: Number of subjects enrolled

Oman: 8

Country: Number of subjects enrolled

Peru: 16

Country: Number of subjects enrolled

Poland: 52

Country: Number of subjects enrolled

Russian Federation: 97

Country: Number of subjects enrolled

Singapore: 11

Country: Number of subjects enrolled

South Africa: 38

Country: Number of subjects enrolled

Spain: 39

Country: Number of subjects enrolled

Sweden: 1

Country: Number of subjects enrolled

Thailand: 30

Country: Number of subjects enrolled

Turkey: 40

Country: Number of subjects enrolled

United States: 162

Worldwide total number of subjects

1072

EEA total number of subjects

361

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

38

Adults (18-64 years)

971

From 65 to 84 years

63

85 years and over

0

Subject disposition

Top of page

Recruitment details

1,072 participants enrolled at 164 sites in 28 countries

Screening details

There were 1,034 adult subjects and 38 adolescent subjects

Period 1 title

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

Ligelizumab 72 mg

Arm description

Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Arm type

Experimental

Investigational medicinal product name

Ligelizumab

Investigational medicinal product code

QGE031

Other name

QGE031

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

liquid in vial for subcutaneous injection

Ligelizumab 120 mg

Arm description

Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Arm type

Experimental

Investigational medicinal product name

Ligelizumab

Investigational medicinal product code

QGE031

Other name

QGE031

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

liquid in vial for subcutaneous injection

Omalizumab 300 mg

Arm description

Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w

Arm type

Experimental

Investigational medicinal product name

Omalizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

liquid in vial for subcutaneous injection

Placebo - QGE031 120mg

Arm description

Placebo and Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Arm type

Experimental

Investigational medicinal product name

Placebo + drug

Investigational medicinal product code

placebo + QGE031

Other name

placebo + QGE031

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

liquid in vial for subcutaneous injection

Number of subjects in period 1	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo - QGE031 120mg
Started	317	324	322	109
Completed	273	267	277	94
Not completed	44	57	45	15
Physician decision	4	5	1	-
Consent withdrawn by subject	19	17	17	7
Adverse event, non-fatal	7	15	6	1
Technical problems	-	-	1	2
No treatment due to mis-randomization	1	-	3	-
Pregnancy	2	3	2	-
Reason unknown	-	1	-	-
Lost to follow-up	2	2	3	1
Lack of efficacy	3	7	2	3
Protocol deviation	6	7	10	1

Baseline characteristics

Top of page

Reporting group title

Ligelizumab 72 mg

Reporting group description

Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Reporting group title

Ligelizumab 120 mg

Reporting group description

Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Reporting group title

Omalizumab 300 mg

Reporting group description

Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w

Reporting group title

Placebo - QGE031 120mg

Reporting group description

Placebo and Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Reporting group values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo - QGE031 120mg	Total
Number of subjects	317	324	322	109	1072
Age Categorical
Adults (971+63=1,034) + Adolescents (38) = Total (1,072)
Units: Participants
<=18 years	10	12	13	3	38
Between 18 and 65 years	288	297	291	95	971
>=65 years	19	15	18	11	63
Age Continuous
Units: Years
arithmetic mean (standard deviation)	43.3 ( 13.12 )	42.3 ( 13.48 )	42.2 ( 13.19 )	0 ( 0 )	-
Sex: Female, Male
Adults (1,034) + Adolescents (38) = Total (1,072)
Units: Participants
Adult\|Female	217	226	218	76	737
Adolescent\|Female	5	9	9	1	24
Adult\|Male	90	86	91	30	297
Adolescent\|Male	5	3	4	2	14
Race/Ethnicity, Customized
All participants: Adult and Adolescent
Units: Subjects
Adult White	226	220	221	80	747
Adolescent White	8	8	8	2	26
Adult Black or African American	1	4	9	1	15
Adolescent Black or African American	0	1	0	0	1
Adult Asian	60	72	64	22	218
Adolescent Asian	0	3	2	0	5
Adult Native Hawaiian or Other Pacific Islander	0	1	0	0	1
Adolescent Native Hawaiian or Pacific Islander	0	0	0	0	0
Adult Native American	12	10	9	3	34
Adolescents Native American	2	0	3	1	6
Adult Multi-racial	6	4	6	0	16
Adolescent Multi-racial	0	0	0	0	0
Adult Race Not Reported	2	1	0	0	3
Adolescent Race Not Reported	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	15.1 ( 1.62 )	14.6 ( 2.01 )	14.7 ( 1.65 )	( )	-

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis sets values	Placebo	Placebo	Placebo	Placebo
Number of subjects	109	106	2	3
Age Categorical
Adults (971+63=1,034) + Adolescents (38) = Total (1,072)
Units: Participants
<=18 years	3
Between 18 and 65 years	95
>=65 years	11
Age Continuous
Units: Years
arithmetic mean (standard deviation)	43.2 ( 14.06 )	( )	( )	( )
Sex: Female, Male
Adults (1,034) + Adolescents (38) = Total (1,072)
Units: Participants
Adult\|Female	76
Adolescent\|Female	2
Adult\|Male	30
Adolescent\|Male	1
Race/Ethnicity, Customized
All participants: Adult and Adolescent
Units: Subjects
Adult White	80
Adolescent White	2
Adult Black or African American	1
Adolescent Black or African American	0
Adult Asian	22
Adolescent Asian	0
Adult Native Hawaiian or Other Pacific Islander	0
Adolescent Native Hawaiian or Pacific Islander	0
Adult Native American	3
Adolescents Native American	1
Adult Multi-racial	0
Adolescent Multi-racial	0
Adult Race Not Reported	0
Adolescent Race Not Reported	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	15.3 ( 2.08 )	( )	( )	( )

End points

Top of page

Reporting group title

Ligelizumab 72 mg

Reporting group description

Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Reporting group title

Ligelizumab 120 mg

Reporting group description

Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Reporting group title

Omalizumab 300 mg

Reporting group description

Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w

Reporting group title

Placebo - QGE031 120mg

Reporting group description

Placebo and Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Placebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48

Primary: Mean change from baseline in UAS7 at Week 12 (Multiple imputation) of Adult subjects (FAS) Within treatment

Top of page

End point title

Mean change from baseline in UAS7 at Week 12 (Multiple imputation) of Adult subjects (FAS) Within treatment ^[1]

End point description

The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours) Itch Severity Score (ISS) is on a scale of 0 to 3. Weekly score (ISS7) is derived by adding up average daily scores of the 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate)

End point type

Primary

End point timeframe

Week 12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	306	312	306	106
Units: score
least squares mean (standard error)	-19.368 ( 0.668 )	-19.330 ( 0.660 )	-20.040 ( 0.663 )	-11.366 ( 1.129 )

Ligelizumab 72 mg vs Placebo Adults

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 72 mg v Placebo

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean

Point estimate

-8.002

Confidence interval

level

95%

sides

2-sided

lower limit

-10.576

upper limit

-5.428

Variability estimate

Standard error of the mean

Dispersion value

1.313

Notes
[2] - Linear mixed model with repeated measures (MMRM)

Ligelizumab 72 mg, Omalizumab 300 mg

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 72 mg v Omalizumab 300 mg

Number of subjects included in analysis

612

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.7628

Method

Mixed models analysis

Parameter type

LS mean

Point estimate

0.672

Confidence interval

level

95%

sides

2-sided

lower limit

-1.169

upper limit

2.513

Variability estimate

Standard error of the mean

Dispersion value

0.939

Notes
[3] - Linear mixed model with repeated measures (MMRM)

Ligelizumab 120 mg, Placebo

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 120 mg v Placebo

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean

Point estimate

-7.964

Confidence interval

level

95%

sides

2-sided

lower limit

-10.522

upper limit

-5.047

Variability estimate

Standard error of the mean

Dispersion value

1.305

Notes
[4] - Linear mixed model with repeated measures (MMRM)

Ligelizumab 120 mg, Omalizumab 300 mg

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 120 mg v Omalizumab 300 mg

Number of subjects included in analysis

618

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.7768

Method

Mixed models analysis

Parameter type

LS mean

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-1.118

upper limit

2.538

Variability estimate

Standard error of the mean

Dispersion value

0.933

Notes
[5] - Linear mixed model with repeated measures (MMRM)

Primary: Mean change from baseline in UAS7 at Week 12 (observed data) of Adolescent subjects (FAS) Within treatment

Top of page

End point title

Mean change from baseline in UAS7 at Week 12 (observed data) of Adolescent subjects (FAS) Within treatment ^[6] ^[7]

End point description

UAS7 up to end of study (Observed data) for adolescents. No Statistical Analysis was planned for adolescent population. UAS is the sum of the HSS and the ISS. UAS7 is the sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. HSS is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours) ISS is on a scale of 0 to 3. Weekly score (ISS7) is derived by adding up average daily scores of the 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate).

End point type

Primary

End point timeframe

Week 12

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned.
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	9	10	12	2
Units: score
arithmetic mean (standard deviation)	-17.39 ( 13.070 )	-14.64 ( 14.662 )	-13.84 ( 15.343 )	-12.75 ( 18.738 )

No statistical analyses for this end point

Secondary: Number and proportion of subjects with UAS7=0 response at Week 12 (Multiple imputation)

Top of page

End point title

Number and proportion of subjects with UAS7=0 response at Week 12 (Multiple imputation) ^[8]

End point description

No Statistical analysis was planed for adolescent group. The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. Complete absence of hives and itch at Week 12

End point type

Secondary

End point timeframe

Week 12

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	306	312	116	106
Units: Participants
Adults	102	104	116	8
Adolescents	3	3	0	1

Ligelizumab 72 mg, Placebo

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 72 mg v Placebo

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.68

Confidence interval

level

95%

sides

2-sided

lower limit

2.667

upper limit

12.095

Notes
[9] - 95% confidence interval for the odds ratio

Ligelizumab 72 mg vs Omalizumab 300 mg

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 72 mg v Omalizumab 300 mg

Number of subjects included in analysis

422

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.843

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.598

upper limit

1.18

Notes
[10] - 95% confidence interval for the odds ratio

Ligelizumab 120 mg vs Placebo

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 120 mg v Placebo

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.734

Confidence interval

level

95%

sides

2-sided

lower limit

2.694

upper limit

12.207

Notes
[11] - 95% confidence interval for the odds ratio

Ligelizumab 120 mg vs Omalizumab 300 mg

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 120 mg v Omalizumab 300 mg

Number of subjects included in analysis

428

Analysis specification

Pre-specified

Analysis type

superiority ^[12]

P-value

= 0.8312

Method

Regression, Logistic

Parameter type

Log odds ratio

Point estimate

0.848

Confidence interval

level

95%

sides

2-sided

lower limit

0.605

upper limit

1.188

Notes
[12] - 95% confidence interval for the odds ratio

Secondary: Mean change from baseline in ISS7 at Week 12 (Multiple Imputation) of Adult subjects (FAS)

Top of page

End point title

Mean change from baseline in ISS7 at Week 12 (Multiple Imputation) of Adult subjects (FAS) ^[13]

End point description

Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate)

End point type

Secondary

End point timeframe

Week 12

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	306	312	306	106
Units: score
least squares mean (standard error)	-8.502 ( 0.305 )	-8.532 ( 0.301 )	-8.921 ( 0.302 )	-5.402 ( 0.514 )

Ligelizumab 120 mg vs Placebo

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 120 mg v Placebo

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority ^[14]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.271

upper limit

-1.929

Variability estimate

Standard error of the mean

Dispersion value

0.597

Notes
[14] - Linear mixed model with repeated measures (MMRM)

Ligelizumab 72 mg vs Placebo

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 72 mg v Omalizumab 300 mg

Number of subjects included in analysis

612

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.8366

Method

Mixed models analysis

Parameter type

LS Mean

Point estimate

0.419

Confidence interval

level

90%

sides

2-sided

lower limit

-0.419

upper limit

1.258

Variability estimate

Standard error of the mean

Dispersion value

0.428

Notes
[15] - Linear mixed model with repeated measures (MMRM)

Ligelizumab 120 mg vs Placebo

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 120 mg v Placebo

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean

Point estimate

-3.13

Confidence interval

level

95%

sides

2-sided

lower limit

-4.295

upper limit

-1.966

Variability estimate

Standard error of the mean

Dispersion value

0.594

Notes
[16] - Adults

Ligelizumab 120 mg vs Omalizumab 300 mg

Statistical analysis description

Treatment contrast in LS mean (change), Adults

Comparison groups

Ligelizumab 120 mg v Omalizumab 300 mg

Number of subjects included in analysis

618

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

= 0.8201

Method

Mixed models analysis

Parameter type

LS Mean

Point estimate

0.389

Confidence interval

level

95%

sides

2-sided

lower limit

-0.444

upper limit

1.222

Variability estimate

Standard error of the mean

Dispersion value

0.425

Notes
[17] - Linear mixed model with repeated measures (MMRM)

Secondary: Mean change from baseline in ISS7 at Week 12 (observed data) of Adolescent subjects, (FAS)

Top of page

End point title

Mean change from baseline in ISS7 at Week 12 (observed data) of Adolescent subjects, (FAS) ^[18]

End point description

Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at Week 12 Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate) No Statistical Analysis was planned for adolescent population.

End point type

Secondary

End point timeframe

Week 12

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	9	10	12	2
Units: score
arithmetic mean (standard deviation)	-8.40 ( 6.779 )	-6.82 ( 7.404 )	-5.10 ( 7.153 )	-7.00 ( 9.899 )

No statistical analyses for this end point

Secondary: Number and Proportion of participants with DLQI score of 0 – 1 at Week 12 (no impact on subject’s quality of life)

Top of page

End point title

Number and Proportion of participants with DLQI score of 0 – 1 at Week 12 (no impact on subject’s quality of life) ^[19]

End point description

Assessed as percentage of subjects achieving DLQI = 0-1 No impact on subjects quality of life at Week 12 The Dermatology life Quality Index (DLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). No statistical anaylsis was planned for adolescent group. No statistical anaylsis was planned for adolescent group.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	306	312	306	106
Units: Participants
Adults	133	150	147	22
Adolescents	3	6	2	1

Ligelizumab 72 mg vs Placebo

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 72 mg v Placebo

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.747

Confidence interval

level

95%

sides

2-sided

lower limit

1.621

upper limit

4.656

Notes
[20] - 95% confidence interval for the odds ratio

Ligelizumab 72 mg vs Omalizumab 300 mg

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 72 mg v Omalizumab 300 mg

Number of subjects included in analysis

612

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

P-value

= 0.8586

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.836

Confidence interval

level

95%

sides

2-sided

lower limit

0.603

upper limit

1.159

Notes
[21] - 95% confidence interval for the odds ratio

Ligelizumab 120 mg vs Placebo

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 120 mg v Placebo

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.261

Confidence interval

level

95%

sides

2-sided

lower limit

1.929

upper limit

5.513

Notes
[22] - 95% confidence interval for the odds ratio

Ligelizumab 120 mg vs Omalizumab 300 mg

Statistical analysis description

Wald chi-square test based on logistic regression

Comparison groups

Ligelizumab 120 mg v Omalizumab 300 mg

Number of subjects included in analysis

618

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

P-value

= 0.519

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.992

Confidence interval

level

95%

sides

2-sided

lower limit

0.717

upper limit

1.373

Notes
[23] - 95% confidence interval for the odds ratio

Secondary: Cumulative number of weeks of AAS7=0 up to week 12 (Multiple Imputation) of Adult subjects (FAS)

Top of page

End point title

Cumulative number of weeks of AAS7=0 up to week 12 (Multiple Imputation) of Adult subjects (FAS) ^[24]

End point description

Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.

End point type

Secondary

End point timeframe

Week 12

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	306	312	306	106
Units: Weeks
least squares mean (standard error)	8.568 ( 0.235 )	8.912 ( 0.239 )	8.790 ( 0.239 )	6.475 ( 0.327 )

Ligelizumab 72 mg vs Placebo

Statistical analysis description

Adults

Comparison groups

Ligelizumab 72 mg v Placebo

Number of subjects included in analysis

412

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Negative binomial regression model

Parameter type

Risk ratio (RR)

Point estimate

1.323

Confidence interval

level

95%

sides

2-sided

lower limit

1.183

upper limit

1.48

Ligelizumab 120 mg vs Placebo

Statistical analysis description

Adults

Comparison groups

Ligelizumab 120 mg v Placebo

Number of subjects included in analysis

418

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Negative binomial regression model

Parameter type

Risk ratio (RR)

Point estimate

1.376

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

1.54

Ligelizumab 120 mg vs Omalizumab 300 mg

Statistical analysis description

Adults

Comparison groups

Ligelizumab 120 mg v Omalizumab 300 mg

Number of subjects included in analysis

618

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3586

Method

Negative binomial regression model

Parameter type

Risk ratio (RR)

Point estimate

1.014

Confidence interval

level

95%

sides

2-sided

lower limit

0.941

upper limit

1.092

Ligelizumab 120 mg vs Omalizumab 300 mg

Statistical analysis description

Adults

Comparison groups

Ligelizumab 72 mg v Omalizumab 300 mg

Number of subjects included in analysis

612

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7469

Method

Negative binomial regression model

Parameter type

Risk ratio (RR)

Point estimate

0.975

Confidence interval

level

95%

sides

2-sided

lower limit

0.904

upper limit

1.051

Secondary: Cumulative number of weeks of AAS7=0 up to week 12 (observed data) of Adolescent subjects (FAS)

Top of page

End point title

Cumulative number of weeks of AAS7=0 up to week 12 (observed data) of Adolescent subjects (FAS) ^[25]

End point description

Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. No Statistical Analysis was planned.

End point type

Secondary

End point timeframe

Week 12

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis were planned.

End point values	Ligelizumab 72 mg	Ligelizumab 120 mg	Omalizumab 300 mg	Placebo
Number of subjects analysed	6	8	10	1
Units: Weeks
least squares mean (standard error)	6.0 ( 4.94 )	7.3 ( 5.44 )	9.0 ( 3.50 )	11.0 ( 0.00 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected after signature of the informed consent form until 30 days after last dose of study treatment, and up to 52 weeks.

Adverse event reporting additional description

AEs and SAEs are any untoward sign or symptom that occurs during the study treatment period and up to 52 weeks.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

QGE031 72mg

Reporting group description

QGE031 72mg

Reporting group title

QGE031 120mg

Reporting group description

QGE031 120mg

Reporting group title

Omalizumab 300mg

Reporting group description

Omalizumab 300mg

Reporting group title

Placebo only

Reporting group description

Placebo only

Reporting group title

Transitioned to QGE031 120mg

Reporting group description

Transitioned to QGE031 120mg

Serious adverse events	QGE031 72mg	QGE031 120mg	Omalizumab 300mg	Placebo only	Transitioned to QGE031 120mg
Total subjects affected by serious adverse events
subjects affected / exposed	22 / 316 (6.96%)	32 / 324 (9.88%)	23 / 319 (7.21%)	3 / 109 (2.75%)	4 / 102 (3.92%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign salivary gland neoplasm
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic lymphocytic leukaemia
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-Hodgkin's lymphoma
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 316 (0.00%)	2 / 324 (0.62%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abortion spontaneous
subjects affected / exposed	1 / 316 (0.32%)	2 / 324 (0.62%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	1 / 316 (0.32%)	2 / 324 (0.62%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sarcoidosis
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	0 / 319 (0.00%)	1 / 109 (0.92%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cervical dysplasia
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Paranasal cyst
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Weight increased
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Clavicle fracture
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	2 / 319 (0.63%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle strain
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal column injury
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 316 (0.32%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Dermoid cyst
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiomyopathy
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Facial paralysis
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	0 / 319 (0.00%)	1 / 109 (0.92%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal adhesions
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 316 (0.32%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis chronic
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 316 (0.32%)	2 / 324 (0.62%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic spontaneous urticaria
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
subjects affected / exposed	1 / 316 (0.32%)	2 / 324 (0.62%)	0 / 319 (0.00%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	3 / 316 (0.95%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 316 (0.00%)	2 / 324 (0.62%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 316 (0.00%)	3 / 324 (0.93%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	2 / 319 (0.63%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paronychia
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 316 (0.32%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	0 / 319 (0.00%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	0 / 316 (0.00%)	0 / 324 (0.00%)	1 / 319 (0.31%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 316 (0.00%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 316 (0.63%)	1 / 324 (0.31%)	0 / 319 (0.00%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	QGE031 72mg	QGE031 120mg	Omalizumab 300mg	Placebo only	Transitioned to QGE031 120mg
Total subjects affected by non serious adverse events
subjects affected / exposed	178 / 316 (56.33%)	182 / 324 (56.17%)	206 / 319 (64.58%)	38 / 109 (34.86%)	43 / 102 (42.16%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	8 / 316 (2.53%)	10 / 324 (3.09%)	5 / 319 (1.57%)	0 / 109 (0.00%)	3 / 102 (2.94%)
occurrences all number	10	11	6	0	4
Aspartate aminotransferase increased
subjects affected / exposed	6 / 316 (1.90%)	8 / 324 (2.47%)	4 / 319 (1.25%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences all number	7	9	4	0	1
Blood creatinine increased
subjects affected / exposed	6 / 316 (1.90%)	8 / 324 (2.47%)	11 / 319 (3.45%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences all number	6	9	13	0	1
Gamma-glutamyltransferase increased
subjects affected / exposed	3 / 316 (0.95%)	7 / 324 (2.16%)	4 / 319 (1.25%)	0 / 109 (0.00%)	2 / 102 (1.96%)
occurrences all number	3	7	5	0	2
SARS-CoV-2 test negative
subjects affected / exposed	2 / 316 (0.63%)	7 / 324 (2.16%)	7 / 319 (2.19%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences all number	2	9	7	0	0
SARS-CoV-2 test positive
subjects affected / exposed	5 / 316 (1.58%)	5 / 324 (1.54%)	8 / 319 (2.51%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences all number	5	5	8	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	7 / 316 (2.22%)	1 / 324 (0.31%)	4 / 319 (1.25%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences all number	11	1	5	1	1
Ligament sprain
subjects affected / exposed	1 / 316 (0.32%)	3 / 324 (0.93%)	7 / 319 (2.19%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences all number	1	3	8	0	1
Vascular disorders
Hypertension
subjects affected / exposed	5 / 316 (1.58%)	6 / 324 (1.85%)	8 / 319 (2.51%)	2 / 109 (1.83%)	1 / 102 (0.98%)
occurrences all number	5	6	8	2	1
Nervous system disorders
Dizziness
subjects affected / exposed	12 / 316 (3.80%)	8 / 324 (2.47%)	2 / 319 (0.63%)	2 / 109 (1.83%)	1 / 102 (0.98%)
occurrences all number	15	20	2	5	1
Headache
subjects affected / exposed	40 / 316 (12.66%)	30 / 324 (9.26%)	39 / 319 (12.23%)	6 / 109 (5.50%)	4 / 102 (3.92%)
occurrences all number	66	68	61	7	6
General disorders and administration site conditions
Fatigue
subjects affected / exposed	4 / 316 (1.27%)	6 / 324 (1.85%)	8 / 319 (2.51%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences all number	4	6	10	0	1
Injection site erythema
subjects affected / exposed	8 / 316 (2.53%)	14 / 324 (4.32%)	5 / 319 (1.57%)	0 / 109 (0.00%)	2 / 102 (1.96%)
occurrences all number	17	29	9	0	8
Injection site pain
subjects affected / exposed	12 / 316 (3.80%)	10 / 324 (3.09%)	4 / 319 (1.25%)	0 / 109 (0.00%)	2 / 102 (1.96%)
occurrences all number	35	24	10	0	8
Injection site reaction
subjects affected / exposed	15 / 316 (4.75%)	15 / 324 (4.63%)	7 / 319 (2.19%)	0 / 109 (0.00%)	6 / 102 (5.88%)
occurrences all number	23	21	9	0	9
Injection site swelling
subjects affected / exposed	7 / 316 (2.22%)	8 / 324 (2.47%)	3 / 319 (0.94%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences all number	14	16	8	0	7
Pyrexia
subjects affected / exposed	13 / 316 (4.11%)	11 / 324 (3.40%)	12 / 319 (3.76%)	4 / 109 (3.67%)	1 / 102 (0.98%)
occurrences all number	15	12	15	4	1
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 316 (0.32%)	6 / 324 (1.85%)	9 / 319 (2.82%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences all number	2	7	13	0	0
Abdominal pain upper
subjects affected / exposed	7 / 316 (2.22%)	5 / 324 (1.54%)	8 / 319 (2.51%)	2 / 109 (1.83%)	2 / 102 (1.96%)
occurrences all number	10	5	8	2	2
Diarrhoea
subjects affected / exposed	10 / 316 (3.16%)	9 / 324 (2.78%)	18 / 319 (5.64%)	4 / 109 (3.67%)	3 / 102 (2.94%)
occurrences all number	10	11	19	4	5
Nausea
subjects affected / exposed	8 / 316 (2.53%)	9 / 324 (2.78%)	10 / 319 (3.13%)	1 / 109 (0.92%)	2 / 102 (1.96%)
occurrences all number	14	12	14	1	2
Toothache
subjects affected / exposed	4 / 316 (1.27%)	9 / 324 (2.78%)	5 / 319 (1.57%)	1 / 109 (0.92%)	3 / 102 (2.94%)
occurrences all number	7	10	5	1	3
Vomiting
subjects affected / exposed	4 / 316 (1.27%)	2 / 324 (0.62%)	2 / 319 (0.63%)	0 / 109 (0.00%)	3 / 102 (2.94%)
occurrences all number	4	2	2	0	3
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	3 / 316 (0.95%)	8 / 324 (2.47%)	6 / 319 (1.88%)	0 / 109 (0.00%)	0 / 102 (0.00%)
occurrences all number	3	11	7	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	10 / 316 (3.16%)	12 / 324 (3.70%)	14 / 319 (4.39%)	1 / 109 (0.92%)	0 / 102 (0.00%)
occurrences all number	10	15	18	1	0
Oropharyngeal pain
subjects affected / exposed	9 / 316 (2.85%)	7 / 324 (2.16%)	18 / 319 (5.64%)	2 / 109 (1.83%)	1 / 102 (0.98%)
occurrences all number	9	8	21	2	1
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	3 / 316 (0.95%)	8 / 324 (2.47%)	0 / 319 (0.00%)	0 / 109 (0.00%)	1 / 102 (0.98%)
occurrences all number	3	8	0	0	1
Angioedema
subjects affected / exposed	4 / 316 (1.27%)	9 / 324 (2.78%)	7 / 319 (2.19%)	2 / 109 (1.83%)	0 / 102 (0.00%)
occurrences all number	10	16	22	2	0
Chronic spontaneous urticaria
subjects affected / exposed	4 / 316 (1.27%)	6 / 324 (1.85%)	12 / 319 (3.76%)	2 / 109 (1.83%)	2 / 102 (1.96%)
occurrences all number	7	19	14	2	2
Dermatitis contact
subjects affected / exposed	4 / 316 (1.27%)	4 / 324 (1.23%)	9 / 319 (2.82%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences all number	5	4	9	1	1
Eczema
subjects affected / exposed	6 / 316 (1.90%)	8 / 324 (2.47%)	11 / 319 (3.45%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences all number	8	11	12	1	1
Urticaria
subjects affected / exposed	17 / 316 (5.38%)	15 / 324 (4.63%)	10 / 319 (3.13%)	2 / 109 (1.83%)	3 / 102 (2.94%)
occurrences all number	20	20	12	2	4
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	9 / 316 (2.85%)	19 / 324 (5.86%)	16 / 319 (5.02%)	1 / 109 (0.92%)	5 / 102 (4.90%)
occurrences all number	9	23	18	1	6
Back pain
subjects affected / exposed	12 / 316 (3.80%)	9 / 324 (2.78%)	16 / 319 (5.02%)	1 / 109 (0.92%)	0 / 102 (0.00%)
occurrences all number	15	13	17	1	0
Myalgia
subjects affected / exposed	2 / 316 (0.63%)	5 / 324 (1.54%)	7 / 319 (2.19%)	3 / 109 (2.75%)	0 / 102 (0.00%)
occurrences all number	2	5	7	3	0
Infections and infestations
Bronchitis
subjects affected / exposed	6 / 316 (1.90%)	3 / 324 (0.93%)	7 / 319 (2.19%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences all number	6	3	7	1	1
COVID-19
subjects affected / exposed	9 / 316 (2.85%)	5 / 324 (1.54%)	12 / 319 (3.76%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences all number	9	5	14	1	1
Gastroenteritis
subjects affected / exposed	9 / 316 (2.85%)	5 / 324 (1.54%)	6 / 319 (1.88%)	3 / 109 (2.75%)	2 / 102 (1.96%)
occurrences all number	10	5	6	3	2
Influenza
subjects affected / exposed	6 / 316 (1.90%)	7 / 324 (2.16%)	11 / 319 (3.45%)	1 / 109 (0.92%)	2 / 102 (1.96%)
occurrences all number	7	8	12	1	3
Nasopharyngitis
subjects affected / exposed	35 / 316 (11.08%)	32 / 324 (9.88%)	38 / 319 (11.91%)	10 / 109 (9.17%)	8 / 102 (7.84%)
occurrences all number	43	46	50	12	9
Rhinitis
subjects affected / exposed	1 / 316 (0.32%)	1 / 324 (0.31%)	7 / 319 (2.19%)	0 / 109 (0.00%)	2 / 102 (1.96%)
occurrences all number	1	2	7	0	2
Sinusitis
subjects affected / exposed	6 / 316 (1.90%)	8 / 324 (2.47%)	6 / 319 (1.88%)	1 / 109 (0.92%)	1 / 102 (0.98%)
occurrences all number	6	8	7	1	1
Upper respiratory tract infection
subjects affected / exposed	20 / 316 (6.33%)	24 / 324 (7.41%)	28 / 319 (8.78%)	4 / 109 (3.67%)	1 / 102 (0.98%)
occurrences all number	25	35	36	5	3
Urinary tract infection
subjects affected / exposed	11 / 316 (3.48%)	10 / 324 (3.09%)	12 / 319 (3.76%)	3 / 109 (2.75%)	5 / 102 (4.90%)
occurrences all number	14	15	14	4	5

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

10 Dec 2019

This amendment provided the following clarifications: 1) A urine dipstick assessment had to be done at Week 24 (and a urine sample sent to central lab for urinalysis if indicated) 2) If subjects were administered omalizumab in the follow-up phase, they had to be discontinued from the study 3) Inclusion of levocetirizine and desloratadine as allowed H1-AH rescue medications

07 Jan 2021

This amendment introduced measures to mitigate the impact of COVID-19 on trial integrity by amending the hierarchical testing strategy to include pooled analysis of secondary endpoints against active comparator and adding COVID-19 related intercurrent events to the primary estimand. This amendment also introduced an interim analysis in order to perform the primary efficacy analysis once all adult patients have completed the treatment period (Week 52). Additional changes in this amendment include: 1) Instruction on Public Health Emergency mitigation procedures: a) Introduction of the use of local laboratory assessments, b) Introduction of remote PRO completion and c) Introduction of phone calls, virtual contacts to replace on-site study visit for the duration of the disruption, 4) Clarification of subject discontinuation: If a subject missed more than 3 consecutive dosing visits then the subject was to be discontinued from the study treatment

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.

The difference of 4 subjects between RAN (1034) vs FAS (1030) is due to mis-randomization of 4 subjects. These subjects did not receive Ligelizumab and hence rightfully not included in FAS (though included in RAN). EMEA-001811-PIP02-15-M04

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Mon May 06 00:21:15 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands