Vaccine Responses in Tralokinumab-Treated Atopic Dermatitis - ECZTRA 5 (ECZema TRAlokinumab Trial No. 5)

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03562377
• Collaborator: (none)
• Enrollment: 215
• Locations: 51
• Arms: 2
• Actual Duration (Months): 16.3
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this trial is to test if treatment with the trial drug, tralokinumab, can affect the body's immune response to vaccines. The trial will also evaluate the efficacy of tralokinumab when it is given concomitantly with vaccines.> The trial includes a screening period of 2 to 6 weeks, a treatment period of 16 weeks (Weeks 0 to 16), and a 14-week off-treatment follow-up period for the assessment of safety (Weeks 16 to 30). Eligible subjects may transfer to an open-label, long-term trial at Week 16 or later.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: Tralokinumab; Drug: Placebo; Biological: Tdap vaccine; Biological: Meningococcal vaccine	Phase 2

Detailed Description

Subjects with atopic dermatitis (AD) will be treated with either tralokinumab or dummy treatment (placebo) for 16 weeks. All subjects will receive 2 vaccines at Week 12. The vaccines are: >

1. Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. This combination vaccine is also known as the Tdap vaccine and is used to prevent these 3 diseases.>

2. Meningococcal vaccine. This vaccine is used to prevent meningococcal diseases (infection of the brain and spinal cord) and blood poisoning.> > The primary objective of the trial is to demonstrate non-inferiority of tralokinumab versus placebo with respect to immune responses to concomitantly administered vaccines.> The secondary objective is to evaluate efficacy of tralokinumab concomitantly administered with vaccines.

Study Design

• Study Type: Interventional
• Actual Enrollment: 215 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Neither the subject nor any of the investigator or LEO staff who are involved in the treatment or clinical evaluation and monitoring of the subjects will be aware of the treatment received. The packaging and labelling of tralokinumab/placebo will contain no evidence of their identity. > Since tralokinumab and placebo are visually distinct and not matched for viscosity, they will be handled and administered by a qualified, unblinded healthcare professional at the trial site who will not be involved in the management of trial subjects.
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Effect of Tralokinumab on Vaccine Antibody Responses in Adults With Moderate-to-severe Atopic Dermatitis Who Are Candidates for Systemic Therapy
• Actual Study Start Date: Jul 13, 2018
• Actual Primary Completion Date: Sep 17, 2019
• Actual Study Completion Date: Nov 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tralokinumab Week 0 to 16:> Tralokinumab will be given as subcutaneous injections. > > Subjects will receive a tralokinumab loading dose at Day 0 followed by tralokinumab injection regimen A. The last administration will occur at Week 14.	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 administration.; Biological: Tdap vaccine; Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. All subjects will receive 1 dose at Week 12.; Biological: Meningococcal vaccine; This vaccine is used to prevent meningococcal diseases (infection of the brain and spinal cord) and blood poisoning. All subjects will receive 1 dose at Week 12.
Placebo Comparator: Placebo Placebo (dummy treatment) will be given as subcutaneous injections. > > Subjects will receive a placebo loading dose at Day 0 followed by placebo injection regimen A. The last administration will occur at Week 14.	Drug: Placebo; Placebo contains the same excipients in the same concentration only lacking tralokinumab.; Biological: Tdap vaccine; Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. All subjects will receive 1 dose at Week 12.; Biological: Meningococcal vaccine; This vaccine is used to prevent meningococcal diseases (infection of the brain and spinal cord) and blood poisoning. All subjects will receive 1 dose at Week 12.

Outcome Measures

Primary Outcome Measures

1. Positive Anti-tetanus Response at Week 16 [Week 12 to Week 16]

   The antibody response to Tdap vaccine will be assessed by measuring serum anti-tetanus IgG by an immunoassay. A positive response is defined as a 3-fold IgG increase compared to Week 12 if IgG ≤1.0 IU/mL at Week 12; or IgG ≥2.5 IU/mL if IgG >1.0 IU/mL at Week 12.

2. Positive Anti-meningococcal Response at Week 16 [Week 12 to Week 16]

   The antibody response to meningococcal vaccine will be assessed by measuring serum anti-meningococcal IgG by an immunoassay. A positive response is defined as IgG ≥3.0 µg/mL with at least a 3-fold increase compared to Week 12.

Secondary Outcome Measures

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

   The 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).

2. Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16. [Week 0 to Week 16]

   The 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.

3. Number of AEs. [Week 0 to Week 16]

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

4. Presence of Anti-drug Antibodies (ADA). [Week 0 to Week 16]

   ADA levels were measured using a validated bioanalytical method. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 54 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:>

• Age 18 to 54 years>

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

• History of AD for ≥1 year >

• Subjects who have a recent history of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable>

• AD involvement of ≥10% body surface area at screening and baseline>

• An EASI score of ≥12 at screening and 16 at baseline>

• An IGA score of ≥3 at screening and at baseline >

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

Exclusion Criteria:>

• Subjects for whom administration of the meningococcal vaccine provided in this trial is contraindicated or medically inadvisable, according to local label of the vaccine>

• Subjects for whom administration of the tetanus, diphtheria, and pertussis vaccine provided in this trial is contraindicated or medically inadvisable, according to local label of the vaccine>

• Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment>

• Use of tanning beds or phototherapy within 6 weeks prior to randomisation>

• Treatment with systemic immunosuppressive/immunomodulating medications and/or systemic corticosteroids within 4 weeks prior to randomisation>

• Treatment with the topical medications topical corticosteroids (TCS), topical calcineurin inhibitor (TCI) or phosphodiesterase 4 (PDE-4) inhibitor within 2 weeks prior to randomisation>

• Receipt of any vaccine (except influenza virus vaccines) within 3 months prior to screening, any meningococcal vaccine within 1 year prior to screening, or any tetanus-, diphtheria-, or pertussis-containing vaccine within 5 years prior to screening>

• Receipt of any marketed (i.e. immunoglobulin, anti-IgE) or investigational biologic agent, including dupilumab>

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leo Pharma Investigational Site	Fort Smith	Arkansas	United States	72916
2	LEO Pharma Investigational Site	Bakersfield	California	United States	93301
3	Leo Pharma Investigational Site	Beverly Hills	California	United States	90212
4	Leo Pharma Investigational Site	Fountain Valley	California	United States	92708
5	Leo Pharma Investigational Site	Los Angeles	California	United States	90025
6	Leo Pharma Investigational Site	Los Angeles	California	United States	90045
7	Leo Pharma Investigational Site	Los Angeles	California	United States	90057
8	Leo Pharma Investigational Site	Newport Beach	California	United States	92660
9	LEO Pharma Investigational Site	San Diego	California	United States	92123
10	LEO Pharma Investigational Site	Centennial	Colorado	United States	80112
11	LEO Pharma Investigational Site	Denver	Colorado	United States	80045
12	LEO Pharma Investigational Site	Thornton	Colorado	United States	80233
13	Leo Pharma Investigational Site	Coral Gables	Florida	United States	33134
14	Leo Pharma Investigational Site	Doral	Florida	United States	33122
15	Leo Pharma Investigational Site	Hialeah	Florida	United States	33012
16	LEO Pharma Investigational Site	Atlanta	Georgia	United States	30328
17	Leo Pharma Investigational Site	New Albany	Indiana	United States	47150
18	Leo Pharma Investigational Site	South Bend	Indiana	United States	46617
19	LEO Pharma Investigational Site	Bangor	Maine	United States	04401
20	Leo Pharma Investigational Site	Boston	Massachusetts	United States	02115
21	LEO Pharma Investigational Site	Brighton	Massachusetts	United States	02135
22	Leo Pharma Investigational Site	Ann Arbor	Michigan	United States	48103
23	LEO Pharma Investigational Site	Southfield	Michigan	United States	48034
24	Leo Pharma Investigational Site	Missoula	Montana	United States	59808
25	Leo Pharma Investigational Site	East Windsor	New Jersey	United States	08520
26	LEO Pharma Investigational Site	Brooklyn	New York	United States	11201
27	Leo Pharma Investigational Site	Cortland	New York	United States	13045
28	Leo Pharma Investigational Site	Forest Hills	New York	United States	11375
29	Leo Pharma Investigational Site	New York	New York	United States	10021
30	Leo Pharma Investigational Site	Cincinnati	Ohio	United States	45219
31	LEO Pharma Investigational Site	Cincinnati	Ohio	United States	45231
32	LEO Pharma Investigational Site	Gahanna	Ohio	United States	43230
33	LEO Pharma Investigational Site	Medford	Oregon	United States	97504
34	Leo Pharma Investigational Site	Chattanooga	Tennessee	United States	37421
35	Leo Pharma Investigational Site	Austin	Texas	United States	78759
36	LEO Pharma Investigational Site	Dallas	Texas	United States	75225
37	Leo Pharma Investigational Site	Frisco	Texas	United States	75034
38	Leo Pharma Investigational Site	South Burlington	Vermont	United States	05403
39	Leo Pharma Investigational Site	Spokane	Washington	United States	99202
40	LEO Pharma Investigational Site	Edmonton	Alberta	Canada	T5K 1X3
41	LEO Pharma Investigational Site	Edmonton	Alberta	Canada	T6G 1C3
42	LEO Pharma Investigational Site	Vancouver	British Colombia	Canada	V6H 4E1
43	LEO Pharma Investigational Site	Saint John's	New Foundland & Labrador	Canada	A1A 4Y3
44	LEO Pharma Investigational Site	Hamilton	Ontario	Canada	L8S 1G5
45	LEO Pharma Investigational Site	London	Ontario	Canada	N6H 5L5
46	LEO Pharma Investigational Site	Oakville	Ontario	Canada	L6J 7W5
47	LEO Pharma Investigational Site	Peterborough	Ontario	Canada	K9J 5K2
48	LEO Pharma Investigational Site	Richmond Hill	Ontario	Canada	L4B 1A5
49	LEO Pharma Investigational Site	Toronto	Ontario	Canada	M4V 1R2
50	LEO Pharma Investigational Site	Windsor	Ontario	Canada	N8X 2G1
51	LEO Pharma Investigational Site	Verdun	Quebec	Canada	H4G 3E7

Sponsors and Collaborators

• LEO Pharma

Investigators

• Study Director: Medical Expert, LEO Pharma

Study Documents (Full-Text)

• Study Protocol - Apr 23, 2018
• Statistical Analysis Plan - Oct 18, 2019

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT03562377
• Other Study ID Numbers: LP0162-1341
• First Posted: Jun 19, 2018
• Last Update Posted: Mar 5, 2021
• Last Verified: Jan 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
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema; Vaccines

Study Results

Participant Flow

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Period Title: Treatment Period
STARTED	107	108
Safety Analysis Set	107	107
Per Protocol Anaysis Set	88	78
Full Analysis Set	106	108
COMPLETED	100	89
NOT COMPLETED	7	19
Period Title: Treatment Period
STARTED	75	75
COMPLETED	16	18
NOT COMPLETED	59	57

Baseline Characteristics

Arm/Group Title	Tralokinumab	Placebo	Total
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Total of all reporting groups
Overall Participants	107	108	215
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	107 100%	108 100%	215 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.0 (11.2)	34.4 (10.8)	34.2 (11.0)
Sex: Female, Male (Count of Participants)
Female	53 49.5%	73 67.6%	126 58.6%
Male	54 50.5%	35 32.4%	89 41.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 15.9%	19 17.6%	36 16.7%
Not Hispanic or Latino	90 84.1%	89 82.4%	179 83.3%
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	16 15%	18 16.7%	34 15.8%
Native Hawaiian or Other Pacific Islander	0 0%	2 1.9%	2 0.9%
Black or African American	25 23.4%	27 25%	52 24.2%
White	62 57.9%	56 51.9%	118 54.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 3.7%	5 4.6%	9 4.2%
Region of Enrollment (participants) [Number]
Canada	34 31.8%	35 32.4%	69 32.1%
United States	73 68.2%	73 67.6%	146 67.9%
Investigator's Global Assessment (IGA) (Count of Participants)
Clear (IGA=0)	0 0%	0 0%	0 0%
Almost clear (IGA=1)	0 0%	0 0%	0 0%
Mild disease (IGA=2)	0 0%	0 0%	0 0%
Moderate disease (IGA=3)	72 67.3%	72 66.7%	144 67%
Severe disease (IGA=4)	34 31.8%	36 33.3%	70 32.6%
Missing	1 0.9%	0 0%	1 0.5%
Eczema Area and Severity Index score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.26 (10.79)	26.75 (11.23)	26.51 (11.00)

Outcome Measures

1. Primary Outcome

Title	Positive Anti-tetanus Response at Week 16
Description	The antibody response to Tdap vaccine will be assessed by measuring serum anti-tetanus IgG by an immunoassay. A positive response is defined as a 3-fold IgG increase compared to Week 12 if IgG ≤1.0 IU/mL at Week 12; or IgG ≥2.5 IU/mL if IgG >1.0 IU/mL at Week 12.
Time Frame	Week 12 to Week 16

Outcome Measure Data

Analysis Population Description

The per protocol analysis set was used for the primary analysis, excluding participants who did not provide vaccine response data at Week 12 (1 participant in the tralokinumab group and 2 participants in the placebo group).

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Measure Participants	87	76
Count of Participants [Participants]	80 74.8%	73 67.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The difference in response rates was calculated using the Mantel-Haenszel estimate of the risk difference stratified by baseline disease severity together with the 2-sided 95% CI. Non-inferiority of tralokinumab was demonstrated if the lower limit of the 95% CI was greater than -25%. Power calculation assumed 160 subjects in the per protocol analysis set, providing 98% power to establish non-inferiority, assuming response rates of 80% in both treatment groups and a non-inferiority margin of -25%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -11.3 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Positive Anti-meningococcal Response at Week 16
Description	The antibody response to meningococcal vaccine will be assessed by measuring serum anti-meningococcal IgG by an immunoassay. A positive response is defined as IgG ≥3.0 µg/mL with at least a 3-fold increase compared to Week 12.
Time Frame	Week 12 to Week 16

Outcome Measure Data

Analysis Population Description

The per protocol analysis set was used for the primary analysis, excluding participants who did not provide vaccine response data at Week 12 (2 participants in each treatment group).

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Measure Participants	86	76
Count of Participants [Participants]	74 69.2%	64 59.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The difference in response rates was calculated using the Mantel-Haenszel estimate of the risk difference stratified by baseline disease severity together with the 2-sided 95% CI. Non-inferiority of tralokinumab was demonstrated if the lower limit of the 95% CI was greater than -25%. Power calculation assumed 160 subjects in the per protocol analysis set, providing 98% power to establish non-inferiority, assuming response rates of 80% in both treatment groups and a non-inferiority margin of -25%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -9.2 to 12.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis of the secondary outcome measures was done for the full analysis set, i.e. all subjects who were randomised and exposed to IMP (tralokinumab/placebo). 1 subject in the tralokinumab group was randomised in error and not exposed to IMP and therefore excluded from the full analysis set.

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Measure Participants	106	108
Count of Participants [Participants]	33 30.8%	21 19.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments	The p-value was adjusted for multiplicity by a pre-specified testing hierarchy. Subjects with missing data or subjects who received rescue medication prior to Week 16 were considered non-responders in the primary analysis of the primary estimand.
	Method	Cochran-Mantel-Haenszel
	Comments	The difference in response rates was analysed using the Cochran-Mantel-Haenszel test stratified by baseline disease severity (moderate or severe).
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95%; 0.2 to 22.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16.
Description	The 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.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

The analysis of the secondary outcome measures was done for the full analysis set, i.e. all participants who were randomised and exposed to IMP (tralokinumab/placebo). 1 participant in the tralokinumab group was randomised in error and not exposed to IMP and therefore excluded from the full analysis set.

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Measure Participants	106	108
Count of Participants [Participants]	52 48.6%	39 36.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tralokinumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments	The p-value was adjusted for multiplicity by a pre-specified testing hierarchy. Subjects with missing data or subjects who received rescue medication prior to Week 16 were considered non-responders in the primary analysis of the primary estimand.
	Method	Cochran-Mantel-Haenszel
	Comments	The difference in response rates was analysed using the Cochran-Mantel-Haenszel test stratified by baseline disease severity (moderate or severe).
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	12.7
	Confidence Interval	(2-Sided) 95%; -0.2 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of AEs.
Description	Overall summary of AEs during the treatment period is presented. For list of SAEs and frequent AEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.
Time Frame	Week 0 to Week 16

Outcome Measure Data

Analysis Population Description

The descriptive analysis was performed on the safety analysis set. The safety analysis set was defined as all participants who received at least 1 dose of IMP during the trial. Subjects who received at least 1 dose of tralokinumab were analysed in the tralokinumab group.

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Measure Participants	107	107
Number [AEs]	112	133

6. Secondary Outcome

Title	Presence of Anti-drug Antibodies (ADA).
Description	ADA levels were measured using a validated bioanalytical method. 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 16

Outcome Measure Data

Analysis Population Description

All subjects in the safety analysis set were included.

Arm/Group Title	Tralokinumab	Placebo
Arm/Group Description	Participants received tralokinumab every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.	Participants received placebo every 2 weeks for 16 weeks, and the Tdap and meningococcal vaccines at Week 12.
Measure Participants	107	107
Positive	2 1.9%	4 3.7%
Perishing	1 0.9%	2 1.9%
Negative	103 96.3%	97 89.8%
No post-baseline ADA assessment	1 0.9%	4 3.7%

Adverse Events

Time Frame	AEs were collected from time of first trial-related activity after the subject had signed the ICF until completion of the clinical trial (defined as the safety follow up visit at Week 30). Non-serious AEs possibly/probably related to IMP and ongoing at the time of trial completion were followed up for 2 weeks or until final outcome, whichever came first. Serious AEs were followed up until final outcome had been established.
Arm/Group Title	Tralokinumab		Placebo
Arm/Group Description	Tralokinumab		Placebo
All Cause Mortality
	Tralokinumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/107 (0.9%)		0/107 (0%)
Serious Adverse Events
	Tralokinumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/107 (2.8%)		3/107 (2.8%)
Cardiac disorders
Myocarditis	0/107 (0%)	0	1/107 (0.9%)	1
Postural orthostatic tachycardia syndrome	1/107 (0.9%)	1	0/107 (0%)	0
Hepatobiliary disorders
Acute hepatic failure	1/107 (0.9%)	1	0/107 (0%)	0
Infections and infestations
Device related infection	1/107 (0.9%)	1	0/107 (0%)	0
Pneumonia	1/107 (0.9%)	1	0/107 (0%)	0
Septic shock	1/107 (0.9%)	1	0/107 (0%)	0
Injury, poisoning and procedural complications
Procedural haemorrhage	0/107 (0%)	0	1/107 (0.9%)	1
Metabolism and nutrition disorders
Failure to thrive	1/107 (0.9%)	1	0/107 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic	0/107 (0%)	0	1/107 (0.9%)	1
Nervous system disorders
Encephalopathy	1/107 (0.9%)	1	0/107 (0%)	0
Status epilepticus	1/107 (0.9%)	1	0/107 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/107 (0.9%)	1	0/107 (0%)	0
Respiratory failure	1/107 (0.9%)	1	0/107 (0%)	0
Vascular disorders
Shock haemorrhagic	1/107 (0.9%)	1	0/107 (0%)	0
Other (Not Including Serious) Adverse Events
	Tralokinumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/107 (25.2%)		25/107 (23.4%)
Gastrointestinal disorders
Abdominal pain	1/107 (0.9%)	1	3/107 (2.8%)	3
Nausea	1/107 (0.9%)	1	3/107 (2.8%)	3
Immune system disorders
Seasonal allergy	3/107 (2.8%)	4	0/107 (0%)	0
Infections and infestations
Upper respiratory tract infection	2/107 (1.9%)	2	5/107 (4.7%)	7
Viral upper respiratory tract infection	10/107 (9.3%)	10	3/107 (2.8%)	4
Nervous system disorders
Headache	3/107 (2.8%)	3	2/107 (1.9%)	2
Skin and subcutaneous tissue disorders
Dermatitis atopic	12/107 (11.2%)	14	13/107 (12.1%)	21

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

LEO Pharma A/S seeks publication of all phase 3 clinical trials in peer-reviewed journals within 18 months after completion or termination of the clinical trial, regardless of whether the findings are positive or negative. If no publication is submitted by LEO Pharma A/S within these 18 months, the investigator has the right to publish the results from the clinical trial generated by him/herself.