Tralokinumab in Combination With Topical Corticosteroids in Subjects With Severe Atopic Dermatitis - ECZTRA 7

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03761537
• Collaborator: (none)
• Enrollment: 277
• Locations: 74
• Arms: 2
• Actual Duration (Months): 21.5
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Primary objective:

To demonstrate that tralokinumab in combination with topical corticosteroids (TCS) is superior to placebo in combination with TCS in treating severe AD in subjects who are not adequately controlled with or have contraindications to oral cyclosporine A (CSA).

Secondary objectives:

To evaluate the efficacy of tralokinumab in combination with TCS on severity and extent of AD, itch, and health-related quality of life compared to placebo in combination with TCS.

To evaluate the safety of tralokinumab in combination with TCS when treating severe AD in subjects who are not adequately controlled with or have contraindications to oral CSA compared to placebo in combination with TCS.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: Tralokinumab; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 277 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre, Phase 3 Trial Investigating the Efficacy, Safety, and Tolerability of Tralokinumab Administered in Combination With Topical Corticosteroids to Adult Subjects With Severe Atopic Dermatitis
• Actual Study Start Date: Dec 13, 2018
• Actual Primary Completion Date: Apr 21, 2020
• Actual Study Completion Date: Sep 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tralokinumab + TCS 4 subcutaneous (SC) injections of tralokinumab 150 mg as a loading dose on Day 0, followed by 2 SC injections of tralokinumab 150 mg every 2 weeks (Q2W) regimen for 26 weeks. The last administration of the Investigational Medicinal Product (IMP) occurred at Week 24. From Day 0 to Week 24, a Topical corticosteroid (TCS) cream was dispensed to the participants at each IMP dosing visit (e.g., Q2W). Participants were instructed to treat active lesions as needed and to discontinue the TCS treatment when control was achieved.	Drug: 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 subcutaneous (SC) administration.
Placebo Comparator: Placebo + TCS 4 subcutaneous (SC) injections of placebo as a loading dose on Day 0, followed by 2 SC injections of placebo every 2 weeks (Q2W) regimen for 26 weeks. The last administration of the Investigational Medicinal Product (IMP) occurred at Week 24. From Day 0 to Week 24, a Topical corticosteroid (TCS) cream was dispensed to the participants at each IMP dosing visit (e.g., Q2W). Participants were instructed to treat active lesions as needed and to discontinue the TCS treatment when control was achieved.	Other: Placebo; Placebo contains the same excipients in the same concentration only lacking tralokinumab.

Outcome Measures

Primary Outcome Measures

1. At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16 [Week 0 to Week 16]

   EASI (Eczema Area and Severity Index) 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.

Secondary Outcome Measures

1. Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 16 [Week 0 to Week 16]

   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'.

2. Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16 [Week 0 to Week 16]

   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.

3. Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16 [Week 0 to Week 16]

   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 health-related quality of life (HRQoL) 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 HRQoL.

4. Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 [Week 16]

   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).

5. At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 26 [Week 0 to Week 26]

   EASI (Eczema Area and Severity Index) 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.

6. Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26 [Week 0 to Week 26]

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

7. Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26 [Week 0 to Week 26]

   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.

8. Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26 [Week 0 to Week 26]

   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 health-related quality of life (HRQoL) 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 HRQoL.

9. Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26 [Week 26]

   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).

10. Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 [Week 0 to Week 40]

    Presence of ADA from Week 0 to Week 40 was measured. Data were reported in the following categories: positive (presence of ADA at baseline and/or presence of ADA at at least 1 post-baseline assessment), perishing (presence of ADA at baseline and absence of ADA at all post-baseline assessments), negative (absence of ADA at all assessments), no post-baseline ADA assessment.

11. Number of Adverse Events From Week 0 to Week 40 [Week 0 to Week 40]

    All adverse events are presented below under Adverse Events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Age 18 and above

• Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD

• History of AD for 1 year or more

• Subjects with a history within 1 year prior to screening of inadequate response to treatment with topical medications or subjects for whom topical treatments are otherwise medically inadvisable

• AD involvement of 10% (or more) body surface area at screening and baseline (visit 3) according to component A of SCORAD

• Documented history of either no previous CSA exposure and not currently a candidate for CSA treatment OR previous exposure to CSA in which case CSA treatment should not be continued or restarted

• Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation

Key Exclusion Criteria:

• Subjects for whom TCSs are medically inadvisable in the opinion of the investigator

• Use of tanning beds or phototherapy (NBUVB, UVB, UVA1, PUVA), within 6 weeks prior to randomisation

• Treatment with immunomodulatory medications or bleach baths within 4 weeks prior to randomisation

• Treatment with topical phosphodiesterase-4 (PDE-4) inhibitor within 2 weeks prior to randomisation

• Receipt of any marketed or investigational biologic agent (e.g. cell-depleting agents or dupilumab) within 6 months prior to randomisation or until cell counts return to normal, whichever is longer

• History of any active skin infection within 1 week prior to randomisation

• History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to randomisation

• A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy

• Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care

• History of any known primary immunodeficiency disorder including a positive HIV test at screening, or the subject taking antiretroviral medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leo Pharma Investigationel Site	Brussels		Belgium	1090
2	Leo Pharma Investigationel Site	Brussels		Belgium	1200
3	Leo Pharma Investigationel Site	Edegem		Belgium	2650
4	Leo Pharma Investigationel Site	Gent		Belgium	9000
5	Leo Pharma Investigationel Site	Gent		Belgium	B-9000
6	Leo Pharma Investigationel Site	Herstal		Belgium	B-4040
7	Leo Pharma Investigationel Site	Kortrijk		Belgium	8500
8	Leo Pharma Investigationel Site	Leuven		Belgium	3000
9	Leo Pharma Investigationel Site	Liège		Belgium	4000
10	Leo Pharma Investigationel Site	Loverval		Belgium	6280
11	Leo Pharma Investigationel Site	Maldegem		Belgium	9990
12	Leo Pharma Investigationel Site	Karlovy Vary		Czechia	36001
13	Leo Pharma Investigationel Site	Kutna Hora		Czechia	284 01
14	Leo Pharma Investigationel Site	Ostrava		Czechia	70852
15	Leo Pharma Investigationel Site	Pardubice		Czechia	53002
16	Leo Pharma Investigationel Site	Prague 5		Czechia	15006
17	Leo Pharma Investigationel Site	Prague 8		Czechia	180 81
18	Leo Pharma Investigationel Site	Prague		Czechia	11000
19	Leo Pharma Investigationel Site	Prague		Czechia	120 00
20	Leo Pharma Investigationel Site	Praha 3		Czechia	130 00
21	Leo Pharma Investigationel Site	Grenoble		France	38000
22	Leo Pharma Investigationel Site	Nice		France	06202
23	Leo Pharma Investigationel Site	Paris		France	75010
24	Leo Pharma Investigationel Site	Pierre-Bénite		France	69495
25	Leo Pharma Investigationel Site	Valence		France	26000
26	Leo Pharma Investigationel Site	Aachen		Germany	52074
27	Leo Pharma Investigationel Site	Augsburg		Germany	86150
28	Leo Pharma Investigationel Site	Bad Bentheim		Germany	48455
29	Leo Pharma Investigationel Site	Berlin		Germany	10117,
30	Leo Pharma Investigationel Site	Dresden		Germany	01307
31	Leo Pharma Investigationel Site	Dülmen		Germany	48249
32	Leo Pharma Investigationel Site	Frankfurt		Germany	60590
33	Leo Pharma Investigationel Site	Halle		Germany	06097
34	Leo Pharma Investigationel Site	Hanover		Germany	30159
35	Leo Pharma Investigationel Site	Jena		Germany	07743
36	Leo Pharma Investigationel Site	Kiel		Germany	24105
37	Leo Pharma Investigationel Site	Mainz		Germany	55128
38	Leo Pharma Investigationel Site	München		Germany	80337
39	Leo Pharma Investigationel Site	Osnabrück		Germany	49074
40	Leo Pharma Investigationel Site	Selters		Germany	56242
41	Leo Pharma Investigationel Site	Białystok		Poland	15-375
42	Leo Pharma Investigationel Site	Bochnia		Poland	32-700
43	Leo Pharma Investigationel Site	Bydgoszcz		Poland	85-094
44	Leo Pharma Investigationel Site	Gdańsk		Poland	80-546
45	Leo Pharma Investigationel Site	Kraków		Poland	30-149
46	Leo Pharma Investigationel Site	Kraków		Poland	31-530
47	Leo Pharma Investigationel Site	Kraków		Poland	31-559
48	Leo Pharma Investigationel Site	Lublin		Poland	20-081
49	Leo Pharma Investigationel Site	Poznań		Poland	60-369
50	Leo Pharma Investigationel Site	Rzeszów		Poland	35-312
51	Leo Pharma Investigationel Site	Warszawa		Poland	01-817
52	Leo Pharma Investigationel Site	Warszawa		Poland	02-625
53	Leo Pharma Investigationel Site	Warszawa		Poland	02-953
54	Leo Pharma Investigationel Site	Wrocław		Poland	51-685
55	Leo Pharma Investigationel Site	Łódź		Poland	90-242
56	Leo Pharma Investigationel Site	Łódź		Poland	90-752
57	Leo Pharma Investigationel Site	Granada	Andalucía	Spain	18014
58	Leo Pharma Investigationel Site	Alicante		Spain	03010
59	Leo Pharma Investigationel Site	Barcelona		Spain	08036
60	Leo Pharma Investigationel Site	Barcelona		Spain	08041
61	Leo Pharma Investigationel Site	Barcelona		Spain	08907
62	Leo Pharma Investigationel Site	Bilbao		Spain	48013
63	Leo Pharma Investigationel Site	Córdoba		Spain	14004
64	Leo Pharma Investigationel Site	Madrid		Spain	28006
65	Leo Pharma Investigationel Site	Madrid		Spain	28046
66	Leo Pharma Investigationel Site	Madrid		Spain	28942
67	Leo Pharma Investigationel Site	Pamplona		Spain	31008
68	Leo Pharma Investigationel Site	Sevilla		Spain	41007
69	Leo Pharma Investigationel Site	Bradford		United Kingdom	BD5 0NA
70	Leo Pharma Investigationel Site	Cottingham		United Kingdom	HU16 5JQ
71	Leo Pharma Investigationel Site	Kirkcaldy		United Kingdom	KY2 5AH
72	Leo Pharma Investigationel Site	London		United Kingdom	E11 1NR
73	Leo Pharma Investigationel Site	Southampton		United Kingdom	SO16 6YD
74	Leo Pharma Investigationel Site	Wakefield		United Kingdom	WF1 4DG

Sponsors and Collaborators

• LEO Pharma

Investigators

• Study Director: Medical Expert, LEO Pharma

Study Documents (Full-Text)

• Study Protocol - Jun 15, 2020
• Statistical Analysis Plan - Oct 21, 2020

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT03761537
• Other Study ID Numbers: LP0162-1346
• First Posted: Dec 3, 2018
• Last Update Posted: Oct 26, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

Participant Flow

Pre-assignment Detail	After the participant gave informed consent, they went through a 2- to 6-week screening period. Eligibility was assessed at the (first) screening visit and on Day 0 (hereinafter "baseline") prior to randomisation.

Arm/Group Title	Tralokinumab + TCS	Placebo + TCS
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.
Period Title: Overall Study
STARTED	140	137
COMPLETED	125	120
NOT COMPLETED	15	17

Baseline Characteristics

Arm/Group Title	Tralokinumab + TCS	Placebo + TCS	Total
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.	Total of all reporting groups
Overall Participants	140	137	277
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	33.0	34.0	34.0
Age, Customized (Count of Participants)
18-64	134 95.7%	131 95.6%	265 95.7%
65-84	6 4.3%	6 4.4%	12 4.3%
Sex: Female, Male (Count of Participants)
Female	58 41.4%	54 39.4%	112 40.4%
Male	82 58.6%	83 60.6%	165 59.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 4.3%	4 2.9%	10 3.6%
Not Hispanic or Latino	134 95.7%	133 97.1%	267 96.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 0.7%	1 0.4%
Native Hawaiian or Other Pacific Islander	1 0.7%	0 0%	1 0.4%
Black or African American	0 0%	1 0.7%	1 0.4%
White	137 97.9%	135 98.5%	272 98.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.4%	0 0%	2 0.7%
Region of Enrollment (Count of Participants)
Belgium	25 17.9%	27 19.7%	52 18.8%
Czechia	14 10%	12 8.8%	26 9.4%
Poland	34 24.3%	43 31.4%	77 27.8%
United Kingdom	5 3.6%	9 6.6%	14 5.1%
France	12 8.6%	7 5.1%	19 6.9%
Germany	22 15.7%	18 13.1%	40 14.4%
Spain	28 20%	21 15.3%	49 17.7%
Age at onset of atopic dermatitis (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	2.5	3.0	3.0
Duration of atopic dermatitis (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	26.0	25.0	26.0
Body surface area with atopic dermatitis (Percentage affected) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Percentage affected]	52.0	52.0	52.0
Investigator's Global Assessment (IGA) (Count of Participants)
Moderate Disease	68 48.6%	70 51.1%	138 49.8%
Severe Disease	70 50%	67 48.9%	137 49.5%
Eczema Area and Severity Index (EASI) (Units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Units on a scale]	28.60	29.10	28.80
Scoring Atopic Dermatitis (SCORAD) (Units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Units on a scale]	69.20	68.90	69.10
Dermatology Life Quality Index (DLQI) (Units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Units on a scale]	16.00	16.00	16.00
Worst Daily Pruritus numeric rating scale (NRS) (weekly average) (Units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Units on a scale]	7.43	7.50	7.43

Outcome Measures

1. Primary Outcome

Title	At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16
Description	EASI (Eczema Area and Severity Index) 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.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS). Of the 277 participants randomised to initial treatment, 275 were treated. Therefore, the FAS consisted of 275 participants (138 participants in the tralokinumab+TCS group + 137 participants in the placebo+TCS group).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the initial treatment period (Week 0 to Week 16) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at Week 0 followed by a dose of 300 mg tralokinumab Q2W from Week 2 to Week 16.	Participants in the initial treatment period (Week 0 to Week 16) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at Week 0 followed by administration of placebo every second week from Week 2 to Week 16.
Measure Participants	138	137
Number [Percentage of responders]	64.2	50.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.018
	Comments	This endpoint was the first endpoint in the sequential testing hierarchy.
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel (MH) test stratified by prior CSA use and baseline disease severity. MH risk differences and standard errors combined by Rubin's rule.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	14.1
	Confidence Interval	(2-Sided) 95%; 2.5 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 16
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'.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

Participants in the full analysis set with a Worst Daily Pruritus NRS (weekly average) of at least 4 at baseline (Week 0).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the initial treatment period (Week 0 to Week 16) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at Week 0 followed by a dose of 300 mg tralokinumab Q2W from Week 2 to Week 16.	Participants in the initial treatment period (Week 0 to Week 16) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at Week 0 followed by administration of placebo every second week from Week 2 to Week 16.
Measure Participants	134	135
Number [Percentage of responders]	45.5	35.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.106
	Comments	This endpoint was the second endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel (MH) test stratified by prior CSA use and baseline disease severity. MH risk differences and standard errors combined by Rubin's rule.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.7
	Confidence Interval	(2-Sided) 95%; -2.0 to 21.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16
Description	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.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the initial treatment period (Week 0 to Week 16) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at Week 0 followed by a dose of 300 mg tralokinumab Q2W from Week 2 to Week 16.	Participants in the initial treatment period (Week 0 to Week 16) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at Week 0 followed by administration of placebo every second week from Week 2 to Week 16.
Measure Participants	138	137
Least Squares Mean (Standard Error) [Units on a scale]	-42.7 (1.6)	-34.1 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	This was the third endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Repeated measurements model
	Comments	Treatment effect at each visit adjusted for baseline SCORAD interacting with each visit, prior CSA, and baseline disease severity (IGA 3 or 4).
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-8.6
	Confidence Interval	(2-Sided) 95%; -13.0 to -4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16
Description	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 health-related quality of life (HRQoL) 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 HRQoL.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

Full Set Analysis (FAS).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the initial treatment period (Week 0 to Week 16) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at Week 0 followed by a dose of 300 mg tralokinumab Q2W from Week 2 to Week 16.	Participants in the initial treatment period (Week 0 to Week 16) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at Week 0 followed by administration of placebo every second week from Week 2 to Week 16.
Measure Participants	137	134
Least Squares Mean (Standard Error) [Units on a scale]	-11.2 (0.4)	-9.6 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.009
	Comments	This was the fourth endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Repeated measurements model
	Comments	Treatment effect at each visit adjusted for baseline DLQI interacting with each visit, prior CSA, and baseline disease severity (IGA 3 or 4).
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
Description	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).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the initial treatment period (Week 0 to Week 16) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at Week 0 followed by a dose of 300 mg tralokinumab Q2W from Week 2 to Week 16.	Participants in the initial treatment period (Week 0 to Week 16) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at Week 0 followed by administration of placebo every second week from Week 2 to Week 16.
Measure Participants	138	137
Number [Percentage of responders]	40.9	26.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.005
	Comments	This endpoint was the fifth endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel (MH) test stratified by prior CSA use and baseline disease severity. MH risk differences and standard errors combined by Rubin's rule.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.6
	Confidence Interval	(2-Sided) 95%; 4.8 to 26.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 26
Description	EASI (Eczema Area and Severity Index) 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.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS).

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.
Measure Participants	138	137
Number [Percentage of responders]	68.8	55.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.014
	Comments	This endpoint was the sixth endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel (MH) test stratified by prior CSA use and baseline disease severity. MH risk differences and standard errors combined by Rubin's rule.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	14.1
	Confidence Interval	(2-Sided) 95%; 2.9 to 25.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26
Description	Subjects will assess their worst itch severity over the past 24 hours using an 11-point numeric rating scale ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

Participants in the full analysis set with a Worst Daily Pruritus NRS (weekly average) of at least 4 at baseline (Week 0).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.
Measure Participants	134	135
Number [Percentage of responders]	47.2	39.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.228
	Comments	This endpoint was the seventh endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Mantel Haenszel
	Comments	HaenszMantelel (MH) test stratified by prior CSA use and baseline disease severity. MH risk differences and standard errors combined by Rubin's rule.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; -4.6 to 19.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26
Description	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.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS).

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.
Measure Participants	138	137
Least Squares Mean (Standard Error) [Units on a scale]	-46.3 (1.5)	-37.3 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	This endpoint was the eighth endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Repeated measurements model
	Comments	Unstructured covariance matrix. Adjusted for baseline SCORAD in interaction with each visit, prior CSA use, and baseline disease severity (IGA 3 or 4)
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-8.9
	Confidence Interval	(2-Sided) 95%; -13.2 to -4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26
Description	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 health-related quality of life (HRQoL) 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 HRQoL.
Time Frame	Week 0 to Week 26

Outcome Measure Data

Analysis Population Description

Full Set Analysis (FAS).

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.
Measure Participants	137	134
Least Squares Mean (Standard Error) [Units on a scale]	-11.5 (0.4)	-9.9 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.005
	Comments	This endpoint was the ninth endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Repeated measurements model
	Comments	Unstructured covariance matrix. Adjusted for baseline DLQI in interaction with each visit, prior CSA use, and baseline disease severity (IGA 3 or 4)
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26
Description	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).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS).

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24.	Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24.
Measure Participants	138	137
Number [Percentage of responders]	47.0	33.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab+TCS, Placebo+TCS
	Comments	Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
Statistical Test of Hypothesis	p-Value	0.014
	Comments	This endpoint was the tenth endpoint in the sequential testing hierarchy. Acceptance of this endpoint depends on prior endpoints' acceptance.
	Method	Mantel Haenszel
	Comments	Mantel-Haenszel (MH) test stratified by prior CSA use and baseline disease severity. MH risk differences and standard errors combined by Rubin's rule.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	14.3
	Confidence Interval	(2-Sided) 95%; 2.9 to 25.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40
Description	Presence of ADA from Week 0 to Week 40 was measured. Data were reported in the following categories: positive (presence of ADA at baseline and/or presence of ADA at at least 1 post-baseline assessment), perishing (presence of ADA at baseline and absence of ADA at all post-baseline assessments), negative (absence of ADA at all assessments), no post-baseline ADA assessment.
Time Frame	Week 0 to Week 40

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tralokinumab+TCS	Placebo+TCS
Arm/Group Description	Participants in the entire trial period, including the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed, and the safety follow-up period (up to Week 40).	Participants in the entire trial period, including the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed, and the safety follow-up period (up to Week 40).
Measure Participants	138	137
Positive	2 1.4%	3 2.2%
Negative	134 95.7%	133 97.1%
Perishing	1 0.7%	1 0.7%
No post-baseline ADA assessment	1 0.7%	0 0%

12. Secondary Outcome

Title	Number of Adverse Events From Week 0 to Week 40
Description	All adverse events are presented below under Adverse Events
Time Frame	Week 0 to Week 40

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Treatment period (Week 0 to Week 26), safety follow-up period (Week 26 to Week 40).
Adverse Event Reporting Description	The analysis was conducted based on the safety analysis set which consisted of subjects exposed to at least 1 dose of investigational medicinal product (IMP e.g., tralokinumab or placebo). In the category Other adverse events (AEs), all AEs will be reported in the safety follow-up period, whereas a frequency threshold at 2% AEs will apply for the treatment period, except that all AEs will be reported if also part of the safety follow-up period.
Arm/Group Title	Treatment Period: Tralokinumab+TCS		Treatment Period: Placebo+TCS		Safety Follow-up Period: Tralokinumab+TCS		Safety Follow-up Period: Placebo+TCS
Arm/Group Description	Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24. For the treatment period, only AEs with a frequency above 2% will be reported. The exception is that AEs reported in the safety follow-up period will also be reported for the treatment period. The total AEs will represent all AEs reported in the treatment period.		Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24. For the treatment period, only AEs with a frequency above 2% will be reported. The exception is that AEs reported in the safety follow-up period will also be reported for the treatment period. The total AEs will represent all AEs reported in the treatment period.		Participants who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the participants during the safety follow-up period. Eligible participants were invited to enter a long-term extension trial conducted under a separate protocol (LP0162-1337, ECZTEND). For the safety follow-up period, all AEs will be reported.		Participants who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the participants during the safety follow-up period. Eligible participants were invited to enter a long-term extension trial conducted under a separate protocol (LP0162-1337, ECZTEND). For the safety follow-up period, all AEs will be reported.
All Cause Mortality
	Treatment Period: Tralokinumab+TCS		Treatment Period: Placebo+TCS		Safety Follow-up Period: Tralokinumab+TCS		Safety Follow-up Period: Placebo+TCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/138 (0%)		0/137 (0%)		0/75 (0%)		0/83 (0%)
Serious Adverse Events
	Treatment Period: Tralokinumab+TCS		Treatment Period: Placebo+TCS		Safety Follow-up Period: Tralokinumab+TCS		Safety Follow-up Period: Placebo+TCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/138 (0.7%)		5/137 (3.6%)		0/75 (0%)		1/83 (1.2%)
Immune system disorders
Anaphylactic reaction	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Infections and infestations
Appendicitis	1/138 (0.7%)	1	0/137 (0%)	0	0/75 (0%)	0	0/83 (0%)	0
Pyelonephritis	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
Injury, poisoning and procedural complications
Peripheral nerve injury	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Seizure	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Psychiatric disorders
Depressed mood	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Suicidal ideation	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/138 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/83 (0%)	0
Other (Not Including Serious) Adverse Events
	Treatment Period: Tralokinumab+TCS		Treatment Period: Placebo+TCS		Safety Follow-up Period: Tralokinumab+TCS		Safety Follow-up Period: Placebo+TCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/138 (77.5%)		108/137 (78.8%)		4/75 (5.3%)		6/83 (7.2%)
Eye disorders
Conjunctivitis allergic	6/138 (4.3%)	8	5/137 (3.6%)	5	0/75 (0%)	0	0/83 (0%)	0
Dry eye	3/138 (2.2%)	3	1/137 (0.7%)	1	0/75 (0%)	0	1/83 (1.2%)	1
Gastrointestinal disorders
Diarrhoea	1/138 (0.7%)	1	5/137 (3.6%)	8	0/75 (0%)	0	0/83 (0%)	0
Dyspepsia	1/138 (0.7%)	1	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Diverticulum intestinal	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
General disorders
Fatigue	4/138 (2.9%)	4	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Injection site pain	4/138 (2.9%)	5	1/137 (0.7%)	3	0/75 (0%)	0	0/83 (0%)	0
Influenza like illness	3/138 (2.2%)	3	0/137 (0%)	0	0/75 (0%)	0	0/83 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/138 (0%)	0	0/137 (0%)	0	1/75 (1.3%)	1	0/83 (0%)	0
Infections and infestations
Viral upper respiratory tract infection	37/138 (26.8%)	53	35/137 (25.5%)	46	2/75 (2.7%)	2	1/83 (1.2%)	1
Upper respiratory tract infection	10/138 (7.2%)	12	10/137 (7.3%)	11	0/75 (0%)	0	0/83 (0%)	0
Folliculitis	6/138 (4.3%)	6	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Conjunctivitis	6/138 (4.3%)	6	2/137 (1.5%)	3	0/75 (0%)	0	0/83 (0%)	0
Oral herpes	5/138 (3.6%)	8	6/137 (4.4%)	6	0/75 (0%)	0	0/83 (0%)	0
Rhinitis	5/138 (3.6%)	6	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Gastroenteritis	4/138 (2.9%)	4	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Pharyngitis	4/138 (2.9%)	4	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Sinusitis	3/138 (2.2%)	4	5/137 (3.6%)	5	0/75 (0%)	0	0/83 (0%)	0
Influenza	3/138 (2.2%)	3	4/137 (2.9%)	4	0/75 (0%)	0	0/83 (0%)	0
Bronchitis	3/138 (2.2%)	4	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Dermatitis infected	2/138 (1.4%)	2	5/137 (3.6%)	10	0/75 (0%)	0	1/83 (1.2%)	1
Nasopharyngitis	1/138 (0.7%)	1	6/137 (4.4%)	6	0/75 (0%)	0	0/83 (0%)	0
Herpes simplex	1/138 (0.7%)	1	3/137 (2.2%)	4	0/75 (0%)	0	0/83 (0%)	0
Tonsillitis	0/138 (0%)	0	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Urinary tract infection	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
Lower respiratory tract infection	0/138 (0%)		2/137 (1.5%)		0/75 (0%)	0	1/83 (1.2%)	1
Pyelonephritis	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
Injury, poisoning and procedural complications
Skin abrasion	3/138 (2.2%)	3	0/137 (0%)	0	0/75 (0%)	0	0/83 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	6/138 (4.3%)	6	4/137 (2.9%)	4	0/75 (0%)	0	0/83 (0%)	0
Myalgia	4/138 (2.9%)	5	2/137 (1.5%)	2	0/75 (0%)	0	0/83 (0%)	0
Arthralgia	2/138 (1.4%)	2	3/137 (2.2%)	3	1/75 (1.3%)	1	0/83 (0%)	0
Musculoskeletal pain	0/138 (0%)	0	3/137 (2.2%)	4	0/75 (0%)	0	0/83 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
Nervous system disorders
Headache	21/138 (15.2%)	25	13/137 (9.5%)	18	0/75 (0%)	0	0/83 (0%)	0
Renal and urinary disorders
Renal cyst	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	4/138 (2.9%)	5	8/137 (5.8%)	9	0/75 (0%)	0	0/83 (0%)	0
Cough	4/138 (2.9%)	5	7/137 (5.1%)	7	0/75 (0%)	0	0/83 (0%)	0
Oropharyngeal pain	1/138 (0.7%)	1	8/137 (5.8%)	8	0/75 (0%)	0	0/83 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis atopic	7/138 (5.1%)	11	16/137 (11.7%)	26	0/75 (0%)	0	2/83 (2.4%)	2
Pruritus	6/138 (4.3%)	12	5/137 (3.6%)	6	0/75 (0%)	0	0/83 (0%)	0
Diffuse alopecia	3/138 (2.2%)	3	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Alopecia areata	0/138 (0%)	0	3/137 (2.2%)	3	0/75 (0%)	0	0/83 (0%)	0
Night sweats	0/138 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/83 (1.2%)	1
Vascular disorders
Hypertension	3/138 (2.2%)	3	7/137 (5.1%)	7	0/75 (0%)	0	0/83 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.