Download PDF

Clinical Trial Results:
A randomised, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of tralokinumab monotherapy in subjects with moderate to severe atopic dermatitis who are candidates for systemic therapy

Summary
EudraCT number	2016-004200-65
Trial protocol	ES FR
Global end of trial date	10 Oct 2019

Results information
Results version number	v1(current)
This version publication date	01 Oct 2020
First version publication date	01 Oct 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

LP0162-1325

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

LEO Pharma A/S

Sponsor organisation address

Industriparken 55, Ballerup, Denmark, 2750

Public contact

Clinical disclosure specialist, LEO Pharma A/S, +45 44945888, disclosure@leo-pharma.com

Scientific contact

disclosure@leo-pharma.com, LEO Pharma A/S, +45 44945888, disclosure@leo-pharma.com

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

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

23 Feb 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Oct 2019

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of tralokinumab compared with placebo in treating moderate-to-severe Atopic dermatitis.

Protection of trial subjects

This clinical trial was conducted to conform to the principles of the Declaration of Helsinki as adopted by the 18th World Medical Association General Assembly, 1964, and subsequent amendments. All subjects received written and verbal information concerning the clinical trial. Subjects were asked to consent that their personal data were recorded, collected, processed and could be transferred to EU and non-EU countries in accordance with any national legislation regulating privacy and data protection. Both during the initial treatment period and the maintenance treatment period, some subjects were randomised to placebo treatment. If medically necessary (i.e. to control intolerable atopic dermatitis [AD] symptoms), rescue treatment for AD could be provided to subjects throughout the trial, both during the initial treatment period and the maintenance treatment period, at the discretion of the investigator. For the first 3 investigational medicinal product (IMP) dosing visits in both the initial treatment period (i.e. Weeks 0, 2, and 4) and in open-label treatment, subjects were monitored after IMP administration for immediate drug reactions for a minimum of 2 hours with vital signs taken every 30 minutes or until stable, whichever was later. Vital signs were documented in the electronic case report forms. Appropriate drugs, such as epinephrine, antihistamines, corticosteroids, etc., and medical equipment to treat acute anaphylactic reactions were immediately available at trial sites, and trial personnel was trained to recognise and respond to anaphylaxis according to local guidelines.

Background therapy

All subjects were to use an emollient twice daily (or more, as needed) for at least 14 days before randomisation and were to continue this treatment throughout the trial.

Evidence for comparator

Actual start date of recruitment

31 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

Spain: 96

Country: Number of subjects enrolled

France: 108

Country: Number of subjects enrolled

Germany: 273

Country: Number of subjects enrolled

United States: 198

Country: Number of subjects enrolled

Japan: 127

Worldwide total number of subjects

802

EEA total number of subjects

477

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)

Adults (18-64 years)

759

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Trial start date: May 30, 2017 Primary completion date: August 7, 2018 Trial completion date: October 14, 2019 The trial was conducted in 5 countries: Germany, France, Spain, the United States, and Japan.

Screening details

The screening period was 2 to 6 weeks and included 1 or 2 visits. The exact duration depended on the wash-out period defined by the exclusion criteria. If no wash-out or only a 2-week wash-out was required, screening Visits 1 and 2 were combined. Eligibility was assessed at the (first) screening visit and on Day 0 prior to randomisation.

Period 1 title

Initial treatment period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Blinding implementation details

This was a double-blind trial in which tralokinumab and placebo were visually distinct from each other. The IMP was handled and administered by a qualified, unblinded healthcare professional (HCP) at the site who was not involved in the management of trial subjects and who did not perform any of the assessments.

Are arms mutually exclusive

Yes

Initial treatment period - Tralokinumab 300 mg Q2W

Arm description

Week 0 to Week 16: Tralokinumab 300 mg Q2W Tralokinumab: Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for SC administration.

Arm type

Experimental

Investigational medicinal product name

Tralokinumb 300 mg Q2W

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

At Day 0, each subject received 4 SC injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab (4.0 mL). At subsequent visits (Q2W) each subject received 2 SC injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. IMP was administered by a qualified, unblinded HCP. The injections were administered into the SC tissue of the upper arm, anterior thigh, or abdomen, separated by at least 3 cm.

Initial treatment period - Placebo Q2W

Arm description

Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab.

Arm type

Placebo

Investigational medicinal product name

Placebo Q2W

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Dosage and administration details: At Day 0, each subject received 4 SC injections (each 1.0 mL) of placebo to receive a total loading dose (4.0 mL). At subsequent visits (Q2W) each subject received 2 SC injections (each 1.0 mL) of placebo IMP was administered by a qualified, unblinded HCP. The injections were administered into the SC tissue of the upper arm, anterior thigh, or abdomen, separated by at least 3 cm.

Number of subjects in period 1	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Started	603	199
Completed	550	179
Not completed	53	20
Discontinued IMP before Week 16	51	18
Not dosed	2	2

Period 2 title

Open-label treatment

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Open-label Treatment: Tralokinumab 300 mg Q2W + optional TCS

Arm description

Week 16 to Week 52: Subjects receiving initial treatment with tralokinumab/placebo Q2W who did not achieve protocol-defined clinical response assigned to open-label treatment at Week 16 with tralokinumab 300 mg Q2W regimen + optional topical corticosteroids (TCS) OR Subjects receiving maintenance treatment with tralokinumab 300 mg Q2W/Q4W or placebo Q2W assigned to open-label treatment after Week 16 with tralokinumab 300 mg Q2W regimen + optional TCS if: -IGA of at least 2 and not achieving EASI75 over at least a 4-week period (over 3 consecutive visits) for subjects with IGA=0 at Week 16; OR -IGA of at least 3 and not achieving EASI75 over at least a 4-week period (i.e. over 3 consecutive visits) for subjects with IGA=1 at Week 16; OR -Not achieving EASI75 over at least a 4-week period (over 3 consecutive visits) for subjects with IGA>1 at Week 16.

Arm type

Experimental

Investigational medicinal product name

Open-label Tralokinumab 300 mg Q2W + Optional TCS

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

At each visit, subject received 2 SC injections (each 1.0 mL) of 150 mg tralokinumab Q2W to receive a total dose of 300 mg. IMP was administered by a qualified HCP. Subjects had the option to self-administer tralokinumab – or have tralokinumab administered by a caregiver – in their home after adequate training by site staff at the investigator’s discretion. The injections were administered into the SC tissue of the upper arm, anterior thigh, or abdomen, separated by at least 3 cm.

Number of subjects in period 2 ^[1]	Open-label Treatment: Tralokinumab 300 mg Q2W + optional TCS
Started	564
Completed	446
Not completed	118
Discontinued IMP	112
Completed Week 50	6

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The open-label treatment period was in parallel to the maintenance treatment period. Subjects from the initial treatment period entered either into the open-label treatment period or maintenance treatment period.

Period 3 title

Maintenance treatment period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Blinding implementation details

This was a double-blind trial in which tralokinumab and placebo were visually distinct from each other. The IMP was handled and administered by a qualified, unblinded HCP at the site who was not involved in the management of trial subjects and who did not perform any of the assessments. Maintenance treatment period was in parallel to the Open-label period.

Are arms mutually exclusive

Yes

Maintenance Treatment Period - Tralokinumab 300 mg Q2W

Arm description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to tralokinumab re-randomised to tralokinumab 300 mg Q2W maintenance dosing regimen.

Arm type

Experimental

Investigational medicinal product name

Maintenance Tralokinumab 300 mg Q2W

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

At each visit, subject received 2 SC injections (each 1.0 mL) of 150 mg tralokinumab Q2W to receive a total dose of 300 mg tralokinumab. IMP was administered by a qualified, unblinded HCP. IMP was administered by a qualified, unblinded HCP. The injections were administered into the SC tissue of the upper arm, anterior thigh, or abdomen, separated by at least 3 cm.

Maintenance Treatment Period - Tralokinumab 300 mg Q4W

Arm description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to tralokinumab re-randomised to tralokinumab 300 mg Q4W maintenance dosing regimen.

Arm type

Experimental

Investigational medicinal product name

Maintenance Tralokinumab 300 mg Q4W

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

At each visit, subject received alternating dose administrations: 2 SC injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab and 2 SC injections (each 1.0 mL) of placebo. IMP was administered by a qualified, unblinded HCP. The injections were administered into the SC tissue of the upper arm, anterior thigh, or abdomen, separated by at least 3 cm.

Maintenance Treatment Period - Placebo Q2W

Arm description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to tralokinumab re-randomised to placebo Q2W dosing regimen.

Arm type

Placebo

Investigational medicinal product name

Maintenance Placebo Q2W

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

At each visit, subject received 2 SC injections (each 1.0 mL) of placebo Q2W to receive a total dose of placebo. IMP was administered by a qualified, unblinded HCP. The injections were administered into the SC tissue of the upper arm, anterior thigh, or abdomen, separated by at least 3 cm.

Maintenance Treatment Period -Placebo Q2W - Tralokinumab Naive

Arm description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to placebo re-assigned to placebo Q2W.

Arm type

Placebo

Investigational medicinal product name

Maintenance Placebo Q2W - Tralokinumab Naive

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 3 ^[2]	Maintenance Treatment Period - Tralokinumab 300 mg Q2W	Maintenance Treatment Period - Tralokinumab 300 mg Q4W	Maintenance Treatment Period - Placebo Q2W	Maintenance Treatment Period -Placebo Q2W - Tralokinumab Naive
Started	71	78	36	29
Completed	44	53	21	15
Not completed	27	25	15	14
Discontinued IMP	4	6	4	4
Completed Week 50	-	-	1	-
Transfer to open-label treatment	21	18	9	10
Not dosed - transfer to open-label	2	1	1	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The maintenance treatment period was in parallel to the open-label treatment period. Subjects from the initial treatment phase entered either into the maintenance treatment period or the open-label treatment period.

Period 4 title

Open-label (Short-term extension)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Open-label Treatment - Tralokinumab 300 mg Q2W + Optional TCS

Arm description

Week 52 to Week 66 [Short term extension (Japan only)]: Japanese subjects who did not achieve protocol-defined clinical response assigned to open-label treatment at Week 16 with tralokinumab 300 mg Q2W regimen + optional topical corticosteroids (TCS) continued an additional 16 weeks (Week 52 to Week 66) of open-label treatment to receive 52 weeks of active therapy. Each subject received 2 SC injections (each 1.0 mL) of 150 mg tralokinumab Q2W to receive a total dose of 300 mg tralokinumab.

Arm type

Experimental

Investigational medicinal product name

Open-label Tralokinumab 300 mg Q2W + Optional TCS

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Number of subjects in period 4 ^[3]	Open-label Treatment - Tralokinumab 300 mg Q2W + Optional TCS
Started	65
Completed	62
Not completed	3
Discontinued IMP	3

Notes
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The open-label treatment period was in parallel to the maintenance treatment period. Subjects from the initial treatment period entered either into the open-label treatment period or maintenance treatment period. This period was relevant only for selected Japanese subjects transferring to open-label treatment after Week 16, so they could receive 52 weeks of active treatment.

Baseline characteristics

Top of page

Reporting group title

Initial treatment period - Tralokinumab 300 mg Q2W

Reporting group description

Reporting group title

Initial treatment period - Placebo Q2W

Reporting group description

Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab.

Reporting group values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W	Total
Number of subjects	603	199	802
Age categorical
Units: Subjects
Adults (18-64 years)	574	185	759
From 65-84 years	28	14	42
85 years and over	1	0	1
Age continuous
Units: years
arithmetic mean (standard deviation)	38.6 ( 13.7 )	39.4 ( 15.2 )	-
Gender categorical
Units: Subjects
Female	252	76	328
Male	351	123	474
Race/Ethnicity
Units: Subjects
White	426	138	564
Black or african american	41	18	59
Asian	120	40	160
American indian or alaska native	1	0	1
Native hawaiian or other pacific islander	5	0	5
Other	8	0	8
Missing	2	3	5
Investigator's Global Assessment
Measure description: The Investigator's Global Assessment (IGA) is an instrument used in clinical trials to rate the severity of the subject's global atopic dermatitis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Units: Subjects
Clear	0	0	0
Almost clear	0	0	0
Mild	0	0	0
Moderate	296	95	391
Severe	305	102	407
Missing	2	2	4
Eczema Area and Severity Index
Measure description: The Eczema Area and Severity Index (EASI) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. Measure Analysis Population Description: Number of subjects analysed = subjects with available data for the baseline parameter.
Units: Units on a scale
arithmetic mean (standard deviation)	32.2 ( 13.7 )	32.9 ( 13.9 )	-
Scoring Atopic Dermatitis
The Scoring Atopic Dermatitis (SCORAD) is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease. Measure Analysis Population Description: Number of subjects analysed = subjects with available data for the baseline parameter.
Units: Units on a scale
arithmetic mean (standard deviation)	70.3 ( 13.0 )	71.7 ( 12.5 )	-
Dermatology Life Quality Index
The Dermatology Life Quality Index (DLQI) consists of 10 items addressing the subject’s perception of the impact of their skin disease on different aspects of their health-related quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0=‘not at all/not relevant’; 1=‘a little’; 2=‘a lot’; 3=‘very much’). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor health-related quality of life.
Units: Units on a scale
arithmetic mean (standard deviation)	16.8 ( 7.1 )	17.0 ( 6.6 )	-
Worst Daily Pruritus Numeric rating scale (weekly average)
Measure description: Subjects assess their worst itch severity over the past 24 hours using an 11-point NRS (Numeric rating scale; 'Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. Measure Analysis Population Description: Number of subjects analysed = subjects with available data for the baseline parameter
Units: Units on a scale
arithmetic mean (standard deviation)	7.7 ( 1.4 )	7.7 ( 1.4 )	-
Body surface area affected by AD
Measure Analysis Population Description: Number of subjects analysed = subjects with available data for the baseline parameter.
Units: percentage affected
arithmetic mean (standard deviation)	52.7 ( 24.1 )	54.2 ( 25.6 )	-
Age of onset of atopic dermatitis (AD)
Measure Analysis Population Description: Number of subjects analysed = subjects with available data for the baseline parameter.
Units: Years
median (inter-quartile range (Q1-Q3))	3.0 (1.0 to 14.0)	3.0 (0.0 to 13.0)	-
Duration of atopic dermatitis
Measure Analysis Population Description: Number of subjects analysed = subjects with available data for the baseline parameter.
Units: Years
arithmetic mean (standard deviation)	27.9 ( 14.5 )	29.6 ( 15.1 )	-

End points

Top of page

Reporting group title

Initial treatment period - Tralokinumab 300 mg Q2W

Reporting group description

Reporting group title

Initial treatment period - Placebo Q2W

Reporting group description

Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab.

Reporting group title

Open-label Treatment: Tralokinumab 300 mg Q2W + optional TCS

Reporting group description

Reporting group title

Maintenance Treatment Period - Tralokinumab 300 mg Q2W

Reporting group description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to tralokinumab re-randomised to tralokinumab 300 mg Q2W maintenance dosing regimen.

Reporting group title

Maintenance Treatment Period - Tralokinumab 300 mg Q4W

Reporting group description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to tralokinumab re-randomised to tralokinumab 300 mg Q4W maintenance dosing regimen.

Reporting group title

Maintenance Treatment Period - Placebo Q2W

Reporting group description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to tralokinumab re-randomised to placebo Q2W dosing regimen.

Reporting group title

Maintenance Treatment Period -Placebo Q2W - Tralokinumab Naive

Reporting group description

Week 16 to Week 52: Subjects achieving a clinical response at Week 16 and initially randomised to placebo re-assigned to placebo Q2W.

Reporting group title

Open-label Treatment - Tralokinumab 300 mg Q2W + Optional TCS

Reporting group description

Primary: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16

Top of page

End point title

Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16

End point description

The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). The full analysis set (FAS: all subjects randomised to initial treatment who were exposed to IMP) was used for the primary analysis; 802 subjects were randomised to initial treatment and 798 received IMP, thus the FAS comprised of 798 subjects.

End point type

Primary

End point timeframe

At Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Number of subjects	95	14

Tralokinumab 300 mg Q2W versus Placebo

Statistical analysis description

The analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rates between tralokinumab and placebo were tested against the 2-sided alternative that there is a difference.

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.002 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

8.6

Confidence interval

level

95%

sides

2-sided

lower limit

4.1

upper limit

13.1

Notes
[1] - Primary endpoints tested sequentially at a 5% significance level.
[2] - Based on primary analysis of primary estimand composite. Subjects with missing data or subjects who received res cue medication prior to Week 16 were considered non-responders. Primary endpoints tested sequentially at a 5% significance level.

Primary: Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Top of page

End point title

Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 16

End point description

The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. The FAS was used for the primary analysis; 802 subjects were randomised to initial treatment and 798 received IMP, thus the FAS comprised of 798 subjects.

End point type

Primary

End point timeframe

At Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Number of subjects	150	25

Tralokinumab 300 mg Q2W versus Placebo

Statistical analysis description

Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rates between tralokinumab and placebo were tested against the 2-sided alternative that there is a difference.

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

12.1

Confidence interval

level

95%

sides

2-sided

lower limit

6.5

upper limit

17.7

Notes
[3] - Based on the primary analysis of primary estimand 'composite'. Subjects with missing data or subjects who received rescue medication prior to Week 16 were considered non-responders. Primary endpoints tested sequentially at a 5% significance level.

Secondary: Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16

Top of page

End point title

Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16

End point description

SCORAD was used to assess the extent and severity of AD. The maximum total score is 103, with higher values indicating more severe disease. The FAS included all randomised subjects.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Adjusted mean change
arithmetic mean (standard error)	-25.2 ( 0.94 )	-14.7 ( 1.80 )

Tralokinumab 300 mg Q2W versus Placebo

Statistical analysis description

Data collected after permanent discontinuation of IMP or initiation of rescue medication not included.

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.001 ^[5]

Method

Repeated measurements model

Parameter type

Difference

Point estimate

-10.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14.4

upper limit

-6.5

Notes
[4] - Multiplicity adjustment using the Holm method.
[5] - Based on the primary analysis of the primary estimand 'hypothetical'. Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0.

Secondary: Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.

Top of page

End point title

Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.

End point description

Subjects assessed their worst itch severity over the past 24 hours using an 11point NRS (‘Worst Daily Pruritus NRS’) with 0 indicating ‘no itch’ and 10 indicating ‘worst itch imaginable’. Number of subjects analysed = subjects with baseline pruritus NRS weekly average ≥4.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	594	194
Units: Number of subjects	119	20

Tralokinumab 300 mg Q2W versus Placebo

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

788

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.002 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

9.7

Confidence interval

level

95%

sides

2-sided

lower limit

4.4

upper limit

Notes
[6] - Multiplicity adjustment using Holm method.
[7] - Based on the primary analysis of the primary estimand 'Composite', subjects who received rescue medication prior to Week 16 or have missing data at Week 16 were considered as non-responders'.

Secondary: Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16

Top of page

End point title

Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16

End point description

The Dermatology Life Quality Index (DLQI) was a validated questionnaire with content specific to those with dermatology conditions. It consisted of 10 items addressing the subject’s perception of the impact of their skin disease on different aspects of their quality of life (QoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Adjusted mean change
arithmetic mean (standard error)	-7.1 ( 0.31 )	-5.0 ( 0.59 )

Tralokinumab 300 mg Q2W versus Placebo

Statistical analysis description

Data collected after permanent discontinuation of IMP or initiation of rescue medication not included.

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.002 ^[9]

Method

Repeated Measurements Model

Parameter type

Difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-0.8

Notes
[8] - Multiplicity adjustment using Holm method.
[9] - Based on the primary analysis of the primary estimand 'hypothetical'. Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0.

Secondary: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16

Top of page

End point title

Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16

End point description

The IGA is an instrument used in clinical trials to rate the severity of the subject’s global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). Maintenance analysis set - Subjects who achieved IGA 0/1 at Week 16 after initial treatment with tralokinumab without use of rescue medication.

End point type

Secondary

End point timeframe

At Week 52

End point values	Maintenance Treatment Period - Tralokinumab 300 mg Q2W	Maintenance Treatment Period - Tralokinumab 300 mg Q4W	Maintenance Treatment Period - Placebo Q2W
Number of subjects analysed	39	36	19
Units: Number of subjects	20	14	9

Tralokinumab 300 mg Q2W versus Placebo

Statistical analysis description

Testing according to the hierarchical testing procedure in the order: IGA 0/1 at Week 52 between Q2W vs Placebo, EASI75 at Week 52 between Q2W vs Placebo, IGA 0/1 at Week 52 between Q4W vs Placebo, and EASI75 at Week 52 between Q4W vs Placebo.

Comparison groups

Maintenance Treatment Period - Tralokinumab 300 mg Q2W v Maintenance Treatment Period - Placebo Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[10]

P-value

= 0.68 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-21.8

upper limit

33.7

Notes
[10] - This test was not statistically significant and hence next maintenance endpoint in the sequential testing procedure was not evaluated.
[11] - Based on the primary analysis of the 'composite' estimand. Subjects who received rescue medication or were transferred to open-labe l treatment were considered non-responders. The P value was considered non-significant.

Tralokinumab 300 mg Q4W versus Placebo

Comparison groups

Maintenance Treatment Period - Placebo Q2W v Maintenance Treatment Period - Tralokinumab 300 mg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

-9.5

Confidence interval

level

95%

sides

2-sided

lower limit

-37.1

upper limit

Secondary: Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16

Top of page

End point title

Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16

End point description

End point type

Secondary

End point timeframe

At Week 52

End point values	Maintenance Treatment Period - Tralokinumab 300 mg Q2W	Maintenance Treatment Period - Tralokinumab 300 mg Q4W	Maintenance Treatment Period - Placebo Q2W
Number of subjects analysed	47	57	30
Units: Number of subjects	28	28	10

Tralokinumab 300 mg Q2W versus Placebo

Statistical analysis description

Comparison groups

Maintenance Treatment Period - Tralokinumab 300 mg Q2W v Maintenance Treatment Period - Placebo Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.056 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

21.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

42.6

Notes
[12] - Test not evaluated for statistical significance. Based on the primary analysis of the 'composite' estimand. Subjects who received rescue medication or were transferred to open-labe l treatment were considered non-responders.

Tralokinumab 300 mg Q4W versus Placebo

Comparison groups

Maintenance Treatment Period - Tralokinumab 300 mg Q4W v Maintenance Treatment Period - Placebo Q2W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.27 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

11.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

Notes
[13] - Test not evaluated for statisitical significance. Based on the primary analysis of the 'composite' estimand. Subjects who received rescue medication or were transferred to open-labe l treatment were considered non-responders.

Secondary: Safety and Tolerability: Adverse event (AE) /Serious adverse event (SAE) Frequency

Top of page

End point title

Safety and Tolerability: Adverse event (AE) /Serious adverse event (SAE) Frequency

End point description

Overall summary of AEs and SAEs during the Initial treatment period is presented. For list of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	602	196
Units: Number of subjects
AE	411	133
SAE	23	8

No statistical analyses for this end point

Secondary: Frequency of Anti-drug Antibodies

Top of page

End point title

Frequency of Anti-drug Antibodies

End point description

Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	602	196
Units: Number of subjects
Total positive	10	3
Pre-existing	0	2
Treatment-boosted	0	0
Treatment emergent	10	1
Perishing	5	3
Negative	564	177
No post-baseline anti-drug antibody assessment	23	13

No statistical analyses for this end point

Secondary: Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Top of page

End point title

Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16

End point description

End point type

Secondary

End point timeframe

At Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Number of subjects	250	42

Tralokinumab 300 mg Q2W vs Placebo Q2W

Statistical analysis description

Based on the primary analysis of the primary estimand 'composite'. Subjects with missing data or subjects who received rescue medication prior to Week 16 were considered non-responders.

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

20.1

Confidence interval

level

95%

sides

2-sided

lower limit

13.3

upper limit

26.8

Notes
[14] - The statistical test was not controlled for multiplicity.

Secondary: Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Top of page

End point title

Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16

End point description

End point type

Secondary

End point timeframe

At Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Number of subjects	87	8

Tralokinumab 300 mg Q2W vs Placebo Q2W

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

10.3

Confidence interval

level

95%

sides

2-sided

lower limit

6.4

upper limit

14.1

Notes
[15] - Based on the primary analysis of the primary estimand 'composite'. Subjects with missing data or subjects who received rescue medication prior to Week 16 were considered non-responders. The statistical test was not controlled for multiplicity.

Secondary: Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score

Top of page

End point title

Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score

End point description

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Units on a scale
least squares mean (confidence interval 95%)	-15.5 (-16.6 to -14.4)	-9.0 (-11.1 to -7.0)

Tralokinumab 300 mg Q2W vs Placebo Q2W

Statistical analysis description

Data collected after permanent discontinuation of IMP or initiation of rescue medication not included. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change will be imputed as 0.

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

Repeated measurements model

Parameter type

Difference of least square means

Point estimate

-6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-8.8

upper limit

-4.1

Notes
[16] - The statistical test was not controlled for multiplicity.

Secondary: Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

Top of page

End point title

Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

End point description

The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.

End point type

Secondary

End point timeframe

At Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Number of subjects	53	6

Tralokinumab 300 mg Q2W vs Placebo Q2W

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[17]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

5.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

8.9

Notes
[17] - Based on the primary analysis of the 'composite' estimand. Subjects who received rescue medication prior to Week 16 or with missing data at Week 16 were considered nonresponders. The statistical test was not controlled for multiplicity.

Secondary: Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

Top of page

End point title

Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

End point description

The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.

End point type

Secondary

End point timeframe

At Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	601	197
Units: Number of subjects	156	23

Tralokinumab 300 mg Q2W vs Placebo Q2W

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[18]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

14.1

Confidence interval

level

95%

sides

2-sided

lower limit

8.6

upper limit

19.6

Notes
[18] - Based on the primary analysis of the 'composite' estimand. Subjects who received rescue medication prior to Week 16 or with missing data at Week 16 were considered non-responders. The statistical test was not controlled for multiplicity.

Secondary: Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average)

Top of page

End point title

Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average)

End point description

Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	598	195
Units: Units on a scale
least squares mean (confidence interval 95%)	-2.6 (-2.8 to -2.4)	-1.7 (-2.1 to -1.3)

Tralokinumab 300 mg Q2W vs Placebo Q2W

Statistical analysis description

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

793

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

Repeated measurements model

Parameter type

Difference of least square means

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

-0.4

Notes
[19] - The statistical test was not controlled for multiplicity.

Secondary: Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16

Top of page

End point title

Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16

End point description

Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. Number of subjects analysed = subjects with baseline Pruritus NRS weekly average of at least 3.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	597	195
Units: Number of subjects	177	28

Tralokinumab 300 mg Q2W vs Placebo Q2W

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[20]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

15.2

Confidence interval

level

95%

sides

2-sided

lower limit

9.2

upper limit

21.3

Notes
[20] - Subjects who received rescue medication prior to Week 16 or have missing data at Week 16 were considered as non-responders. The statistical test was not controlled for multiplicity.

Secondary: Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4

Top of page

End point title

Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4

End point description

The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL. Number of subjects analysed = subjects with baseline DLQI ≥4.

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Initial treatment period - Tralokinumab 300 mg Q2W	Initial treatment period - Placebo Q2W
Number of subjects analysed	578	190
Units: Number of subjects	258	60

Tralokinumab 300 mg Q2W vs Placebo Q2W

Comparison groups

Initial treatment period - Tralokinumab 300 mg Q2W v Initial treatment period - Placebo Q2W

Number of subjects included in analysis

768

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.4

upper limit

20.5

Notes
[21] - Subjects who received rescue medication prior to Week 16 or have missing data at Week 16 were considered as non-responders. The statistical test was not controlled for multiplicity.

Adverse events

Top of page

Timeframe for reporting adverse events

Timeframe for AE

Adverse event reporting additional description

AE additional description

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Initial Period - Tralokinumab Q2W

Reporting group description

Reporting group title

Initial Period - Placebo

Reporting group description

Reporting group title

Maintenance Period - Tralokinumab Q2W

Reporting group description

Reporting group title

Maintenance Period - Tralokinumab Q4W

Reporting group description

Reporting group title

Maintenance Period - Placebo

Reporting group description

Reporting group title

Maintenance Period - Placebo - Tralokinumab Naive

Reporting group description

Reporting group title

Open-label Period - Tralokinumab Q2W + Optional TCS

Reporting group description

Reporting group title

Safety Follow-up

Reporting group description

Serious adverse events	Initial Period - Tralokinumab Q2W	Initial Period - Placebo	Maintenance Period - Tralokinumab Q2W	Maintenance Period - Tralokinumab Q4W	Maintenance Period - Placebo	Maintenance Period - Placebo - Tralokinumab Naive	Open-label Period - Tralokinumab Q2W + Optional TCS	Safety Follow-up
Total subjects affected by serious adverse events
subjects affected / exposed	23 / 602 (3.82%)	8 / 196 (4.08%)	1 / 68 (1.47%)	3 / 76 (3.95%)	0 / 35 (0.00%)	1 / 29 (3.45%)	27 / 563 (4.80%)	16 / 595 (2.69%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive breast carcinoma
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	2 / 563 (0.36%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Accelerated hypertension
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Granuloma
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Injection site reaction
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Strangulated hernia
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst ruptured
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 602 (0.17%)	1 / 196 (0.51%)	0 / 68 (0.00%)	1 / 76 (1.32%)	0 / 35 (0.00%)	1 / 29 (3.45%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	1 / 76 (1.32%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Investigations
Troponin increased
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Accessory cardiac pathway
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute left ventricular failure
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	3 / 563 (0.53%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure acute
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Nervous system disorders
Ataxia
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Carpal tunnel syndrome
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Hypertensive encephalopathy
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Eosinophilia
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Lens dislocation
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Ulcerative keratitis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Incarcerated umbilical hernia
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Hepatitis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	4 / 602 (0.66%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	2 / 563 (0.36%)	3 / 595 (0.50%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dermatitis exfoliative generalised
subjects affected / exposed	2 / 602 (0.33%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	2 / 595 (0.34%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dermatomyositis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperhidrosis
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyoderma gangrenosum
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Stag horn calculus
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	1 / 76 (1.32%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 602 (0.17%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	2 / 563 (0.36%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	1 / 68 (1.47%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 602 (0.00%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Furuncle
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis bacterial
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Keratitis bacterial
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Keratitis viral
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	1 / 595 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Leishmaniasis
subjects affected / exposed	1 / 602 (0.17%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	1 / 76 (1.32%)	0 / 35 (0.00%)	0 / 29 (0.00%)	0 / 563 (0.00%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 602 (0.00%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	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	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Initial Period - Tralokinumab Q2W	Initial Period - Placebo	Maintenance Period - Tralokinumab Q2W	Maintenance Period - Tralokinumab Q4W	Maintenance Period - Placebo	Maintenance Period - Placebo - Tralokinumab Naive	Open-label Period - Tralokinumab Q2W + Optional TCS	Safety Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	351 / 602 (58.31%)	114 / 196 (58.16%)	37 / 68 (54.41%)	39 / 76 (51.32%)	20 / 35 (57.14%)	9 / 29 (31.03%)	304 / 563 (54.00%)	29 / 595 (4.87%)
Investigations
Liver function test increased
subjects affected / exposed	4 / 602 (0.66%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	2 / 35 (5.71%)	0 / 29 (0.00%)	1 / 563 (0.18%)	0 / 595 (0.00%)
occurrences all number	4	0	0	0	2	0	1	0
Injury, poisoning and procedural complications
Wrong patient received medication
subjects affected / exposed	8 / 602 (1.33%)	1 / 196 (0.51%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	2 / 29 (6.90%)	2 / 563 (0.36%)	0 / 595 (0.00%)
occurrences all number	13	1	0	0	0	2	2	0
Nervous system disorders
Headache
subjects affected / exposed	28 / 602 (4.65%)	10 / 196 (5.10%)	6 / 68 (8.82%)	2 / 76 (2.63%)	3 / 35 (8.57%)	0 / 29 (0.00%)	22 / 563 (3.91%)	1 / 595 (0.17%)
occurrences all number	50	16	12	2	6	0	29	1
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	24 / 602 (3.99%)	0 / 196 (0.00%)	5 / 68 (7.35%)	7 / 76 (9.21%)	1 / 35 (2.86%)	0 / 29 (0.00%)	28 / 563 (4.97%)	0 / 595 (0.00%)
occurrences all number	47	0	13	21	1	0	60	0
Eye disorders
Conjunctivitis allergic
subjects affected / exposed	16 / 602 (2.66%)	3 / 196 (1.53%)	3 / 68 (4.41%)	1 / 76 (1.32%)	2 / 35 (5.71%)	0 / 29 (0.00%)	13 / 563 (2.31%)	2 / 595 (0.34%)
occurrences all number	16	4	3	1	2	0	14	2
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	10 / 602 (1.66%)	1 / 196 (0.51%)	4 / 68 (5.88%)	0 / 76 (0.00%)	0 / 35 (0.00%)	0 / 29 (0.00%)	5 / 563 (0.89%)	1 / 595 (0.17%)
occurrences all number	11	1	4	0	0	0	5	1
Oropharyngeal pain
subjects affected / exposed	10 / 602 (1.66%)	1 / 196 (0.51%)	1 / 68 (1.47%)	0 / 76 (0.00%)	2 / 35 (5.71%)	0 / 29 (0.00%)	10 / 563 (1.78%)	0 / 595 (0.00%)
occurrences all number	11	1	1	0	2	0	10	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	152 / 602 (25.25%)	75 / 196 (38.27%)	11 / 68 (16.18%)	14 / 76 (18.42%)	13 / 35 (37.14%)	6 / 29 (20.69%)	123 / 563 (21.85%)	10 / 595 (1.68%)
occurrences all number	198	123	14	22	18	10	201	12
Pruritus
subjects affected / exposed	32 / 602 (5.32%)	10 / 196 (5.10%)	2 / 68 (2.94%)	4 / 76 (5.26%)	1 / 35 (2.86%)	2 / 29 (6.90%)	20 / 563 (3.55%)	0 / 595 (0.00%)
occurrences all number	41	15	2	5	1	2	27	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	5 / 602 (0.83%)	2 / 196 (1.02%)	3 / 68 (4.41%)	4 / 76 (5.26%)	0 / 35 (0.00%)	1 / 29 (3.45%)	18 / 563 (3.20%)	0 / 595 (0.00%)
occurrences all number	5	2	3	4	0	1	19	0
Tendonitis
subjects affected / exposed	3 / 602 (0.50%)	0 / 196 (0.00%)	0 / 68 (0.00%)	0 / 76 (0.00%)	0 / 35 (0.00%)	2 / 29 (6.90%)	6 / 563 (1.07%)	0 / 595 (0.00%)
occurrences all number	3	0	0	0	0	2	6	0
Infections and infestations
Bronchitis
subjects affected / exposed	11 / 602 (1.83%)	4 / 196 (2.04%)	3 / 68 (4.41%)	7 / 76 (9.21%)	2 / 35 (5.71%)	1 / 29 (3.45%)	14 / 563 (2.49%)	1 / 595 (0.17%)
occurrences all number	12	4	3	8	2	1	15	1
Conjunctivitis
subjects affected / exposed	43 / 602 (7.14%)	4 / 196 (2.04%)	3 / 68 (4.41%)	4 / 76 (5.26%)	0 / 35 (0.00%)	0 / 29 (0.00%)	41 / 563 (7.28%)	4 / 595 (0.67%)
occurrences all number	50	4	3	6	0	0	52	4
Influenza
subjects affected / exposed	18 / 602 (2.99%)	5 / 196 (2.55%)	4 / 68 (5.88%)	3 / 76 (3.95%)	1 / 35 (2.86%)	0 / 29 (0.00%)	7 / 563 (1.24%)	2 / 595 (0.34%)
occurrences all number	18	5	5	3	1	0	7	2
Nasopharyngitis
subjects affected / exposed	15 / 602 (2.49%)	2 / 196 (1.02%)	0 / 68 (0.00%)	3 / 76 (3.95%)	2 / 35 (5.71%)	0 / 29 (0.00%)	5 / 563 (0.89%)	1 / 595 (0.17%)
occurrences all number	16	2	0	3	2	0	5	1
Viral upper respiratory tract infection
subjects affected / exposed	139 / 602 (23.09%)	41 / 196 (20.92%)	14 / 68 (20.59%)	18 / 76 (23.68%)	4 / 35 (11.43%)	2 / 29 (6.90%)	143 / 563 (25.40%)	12 / 595 (2.02%)
occurrences all number	172	54	17	26	5	4	201	12

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Aug 2017

The reason for the amendment was due to a request for changes from the Health Authorities in Europe after their review of the protocol. The main amendments are listed below. 1) It was clarified that all subjects in the trial will have a safety follow-up visit (end of trial visit) 16 weeks after last injection of IMP (investigational medicinal product), including those that are offered participation in the long-term extension trial conducted under a separate protocol (LP0162 1337). This was to ensure that safety follow-up information was collected for all subjects enrolled in this trial, and to ensure that a safety evaluation could be made based on data collected after IMP had been discontinued. Furthermore, the evaluation of anti-drug antibodies was considered to be most reliable when samples are taken in the absence of IMP. 2) 2 additional blood samples (PK and anti drug antibodies) were added at Week 4 to better monitor potential development of immunogenicity. 3) The transfer criteria to open-label treatment was changed to keep subjects who entered maintenance treatment with IGA 0/1 in maintenance treatment until they have a sustained 2 step change in IGA (IGA of 0 becoming ≥2; IGA of 1 becoming ≥3). 4) The exclusion criteria regarding receipt of any marketed (i.e. immunoglobulin, anti-IgE) or investigational biologic agent was updated with dupilumab since it was then approved in USA. 5) Infusion reactions were deleted from the risk list since they are not relevant for this trial. Malignancies and interference with reproductive function were added to align with the Investigator’s Brochure. 6) It was clarified that subjects who permanently discontinue IMP prior to Week 16 should also be assessed at the nominal Week 16 visit. This was to allow sensitivity analyses of primary endpoints and secondary endpoints in the initial treatment period. 7) The procedure for emergency unblinding of the individual subject’s treatment was clarified.

12 Dec 2017

The reason for the amendment is due to a request for changes from the Health Authorities in the US after their review of the protocol. The main amendments are listed below. 1) Several 'other endpoints' were included to the trial objectives and endpoints to allow for an evaluation of the efficacy of tralokinumab over time on severity and extent of AD, itch, and health-related quality of life compared with placebo. Additional endpoints were included to evaluate the patient-reported outcomes and health care resource utilisation. 2) Clarification that transfer to open-label requires a persistent worsening of disease observed over 3 consecutive visits in the maintenance period was included. 3) Clarification of how Worst Daily Pruritus NRS at baseline will be calculated was included. 4) Clarification that female subjects of childbearing potential must have used a highly effective form of birth control for at least 1 month prior to baseline was included. 5) Clarification that the small biomarker panel may include more than 7 biomarkers. 6) Clarification that AE reporting starts at screening, not baseline was included. 7) For all randomised subjects the reasons for permanent discontinuation of IMP and for leaving the trial will be presented.

14 Aug 2018

The main reason for the amendment was that a new anti-drug antibody (ADA) assay had been developed with improved tralokinumab tolerance. It meant that the presence or absence of anti-drug antibodies (ADA) could be determined in serum samples with tralokinumab present. Previously, this was not possible and therefore ADA sampling at the end of the 14-week off-treatment safety follow-up was originally required for the ADA evaluation. Thus, the new ADA assay would allow eligible subjects who have completed the treatment periods of trial LP0162 1325 to continue into the long-term extension trial (conducted under a separate protocol [LP0162 1337, ECZTEND]) without completing the safety follow-up period in the present trial. These subjects would have their safety follow-up period after end-of-treatment in the long-term extension trial.

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

Clinical Trial Results: A randomised, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of tralokinumab monotherapy in subjects with moderate to severe atopic dermatitis who are candidates for systemic therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16

Primary: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16

Primary: Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Primary: Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Secondary: Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16

Secondary: Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16

Secondary: Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.

Secondary: Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.

Secondary: Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16

Secondary: Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16

Secondary: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16

Secondary: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16

Secondary: Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16

Secondary: Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16

Secondary: Safety and Tolerability: Adverse event (AE) /Serious adverse event (SAE) Frequency

Secondary: Safety and Tolerability: Adverse event (AE) /Serious adverse event (SAE) Frequency

Secondary: Frequency of Anti-drug Antibodies

Secondary: Frequency of Anti-drug Antibodies

Secondary: Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Secondary: Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Secondary: Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Secondary: Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16

Secondary: Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score

Secondary: Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score

Secondary: Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

Secondary: Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

Secondary: Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

Secondary: Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16

Secondary: Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average)

Secondary: Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average)

Secondary: Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16

Secondary: Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16

Secondary: Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4

Secondary: Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A randomised, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of tralokinumab monotherapy in subjects with moderate to severe atopic dermatitis who are candidates for systemic therapy