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Tralokinumab Monotherapy for Adolescent Subjects With Moderate to Severe Atopic Dermatitis - ECZTRA 6 (ECZema TRAlokinumab Trial no. 6).

Sponsor
LEO Pharma (Industry)
Overall Status
Completed
CT.gov ID
NCT03526861
Collaborator
(none)
301
Enrollment
87
Locations
8
Arms
32.9
Actual Duration (Months)
3.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary objective:

To evaluate the efficacy of subcutaneous (SC) administration of tralokinumab compared with placebo in treating adolescent subjects (age 12 to <18 years) with moderate-to-severe AD.

Secondary objectives:

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

To investigate the safety, immunogenicity, and tolerability of SC administration of tralokinumab compared with placebo when used to treat adolescent subjects (age 12 to <18 years) with moderate-to-severe AD.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
301 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 the investigational medicinal products (IMPs) will contain no evidence of their identity. Since tralokinumab and placebo are visually distinct and not matched for viscosity, IMP will be handled and administered by a qualified, unblinded healthcare professional at the site who will not be involved in the management of trial subjects and who will not perform any of the assessments.
Primary Purpose:
Treatment
Official Title:
A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Trial to Evaluate the Efficacy, Safety, and Tolerability of Tralokinumab Monotherapy in Adolescent Subjects With Moderate-to-severe Atopic Dermatitis (AD) Who Are Candidates for Systemic Therapy
Actual Study Start Date :
Jun 19, 2018
Actual Primary Completion Date :
Apr 15, 2020
Actual Study Completion Date :
Mar 16, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tralokinumab(Dose1) initial-> Tralokinumab(Dose1) maintenanceA

Week 0 to 16 (initial period): Tralokinumab (Dose 1) loading SC injection on Day 0 followed by tralokinumab (Dose 1) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 1) maintenance SC injection regimen A.

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
Experimental: Tralokinumab(Dose1) initial-> Tralokinumab(Dose1) maintenanceB

Week 0 to 16 (initial period): Tralokinumab (Dose 1) loading SC injection on Day 0 followed by tralokinumab (Dose 1) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 1) maintenance SC injection regimen B.

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
Experimental: Tralokinumab(Dose2) initial-> Tralokinumab(Dose2) maintenanceA

Week 0 to 16 (initial period): Tralokinumab (Dose 2) loading SC injection on Day 0 followed by tralokinumab (Dose 2) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 2) maintenance SC injection regimen A.

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
Experimental: Tralokinumab(Dose2) initial-> Tralokinumab(Dose2) maintenanceB

Week 0 to 16 (initial period): Tralokinumab (Dose 2) loading SC injection on Day 0 followed by tralokinumab (Dose 2) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 2) maintenance SC injection regimen B.

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
Experimental: Placebo initial-> Placebo maintenance

Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 52 (maintenance period): Placebo continuation SC injection regimen A.

Drug: Placebos
Placebo contains the same excipients in the same concentration only lacking tralokinumab.
Other Names:
  • Placebo

    		•
    Experimental: Tralokinumab (Dose1) initial-> Open-label tralokinumab

    Week 0 to 16 (initial period): Tralokinumab (Dose 1) loading SC injection on Day 0 followed by tralokinumab (Dose 1) injection regimen A. Week 16 to 52: Tralokinumab (Dose 1) maintenance SC regimen A - open-label with allowed use of topical corticosteroids

    Drug: Tralokinumab
    Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
    Experimental: Tralokinumab (Dose2) initial-> Open-label tralokinumab

    Week 0 to 16 (initial period): Tralokinumab (Dose 2) loading SC injection on Day 0 followed by tralokinumab (Dose 2) injection regimen A. Week 16 to 52: Tralokinumab (Dose 1) maintenance SC regimen A - open-label with allowed use of topical corticosteroids

    Drug: Tralokinumab
    Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
    Experimental: Placebo initial-> Open-label tralokinumab

    Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 52: Tralokinumab (Dose 1) maintenance SC regimen A - open-label with allowed use of topical corticosteroids

    Drug: Tralokinumab
    Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.

    Drug: Placebos
    Placebo contains the same excipients in the same concentration only lacking tralokinumab.
    Other Names:
  • Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

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

      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).

    2. Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 [At Week 16]

      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.

    Secondary Outcome Measures

    1. Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16 [At Week 16]

      The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.

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

      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.

    3. Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16 [From Week 0 to Week 16]

      The CDLQI 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 various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point Likert scale (0 = 'not at all'; 1 = 'only a little'; 2 = 'quite a lot'; 3 = 'very much'). Item 7 (on school time) has one additional response category 'prevented school', which is also scored '3'. The total score of the CDLQI is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.

    4. Number of Adverse Events [From Week 0 to Week 16]

      Number of AEs during the Initial treatment period is presented. For a summary of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the initial treatment period, maintenance treatment period, open-label treatment period, and safety follow-up period, see the Adverse Events Overview section.

    5. Presence of Anti-drug Antibodies [From Week 0 to Week 16]

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

    6. Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16. [At Week 16]

      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.

    7. Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16. [At Week 16]

      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.

    8. Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16 [From 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 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.

    9. Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16 [At Week 16]

      The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.

    10. Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16 [At Week 16]

      The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.

    11. Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16 [From Week 0 to Week 16]

      The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.

    12. Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16 [At Week 16]

      The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.

    13. Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16 [From Week 0 to Week 16]

      The POEM is a validated questionnaire used to assess disease symptoms in atopic eczema patients in both clinical practice and clinical trials. The tool consists of 7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness). Subjects will score how often they have experienced each symptom over the previous week on a 5-point categorical response scale (0 = 'no days'; 1 = '1 to 2 days'; 2 = '3 to 4 days'; 3 = '5 to 6' days; 4 = 'every day'). The total score is the sum of the 7 items (range 0 to 28) and reflects disease-related morbidity; a high score is indicative of a worse disease severity.

    14. Tralokinumab Serum Trough Concentration at Week 16 [At Week 16]

      Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.

    15. Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 [At Week 52]

      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).

    16. Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 [At Week 52]

      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.

    17. Tralokinumab Serum Trough Concentration at Week 66 [At Week 66]

      Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age 12 to 17.

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

    • History of AD for ≥1 year.

    • History of topical corticosteroid (TCS; Europe: Class 3 or higher; US: Class 4 or lower) and/or topical calcineurin inhibitor (TCI) treatment failure or subjects for whom these topical AD treatments are medically inadvisable.

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

    • Stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation.

    Exclusion Criteria:

    • Active dermatologic conditions that may confound the diagnosis of AD.

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

    • Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to randomisation.

    • Treatment with TCS, TCI, or topical phosphodiesterase 4 (PDE-4) inhibitor within 2 weeks prior to randomisation.

    • Receipt of any marketed biological therapy (i.e. immunoglobulin, anti immunoglobulin

    1. including dupilumab or investigational biologic agents.

    • Active skin infection within 1 week prior to randomisation.

    • Clinically significant infection within 4 weeks prior to randomisation.

    • A helminth parasitic infection within 6 months prior to the date informed consent is obtained.

    • Tuberculosis requiring treatment within the 12 months prior to screening.

    • Known primary immunodeficiency disorder.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 LEO Pharma Investigational Site Birmingham Alabama United States 35209
    2 LEO Pharma Investigational Site Fort Smith Arkansas United States 72916
    3 Leo Pharma Investigational Site Fountain Valley California United States 92708
    4 LEO Pharma Investigational Site Los Angeles California United States 90045
    5 LEO Pharma Investigational Site San Francisco California United States 94132
    6 LEO Pharma Investigational Site Stanford California United States 94304
    7 LEO Pharma Investigational Site New Haven Connecticut United States 06520-8059
    8 LEO Pharma Investigational Site Miami Florida United States 33137
    9 Leo Pharma Investigational Site Albany Georgia United States 31707
    10 LEO Pharma Investigational Site Chicago Illinois United States 60611
    11 LEO Pharma Investigational Site Louisville Kentucky United States 40215
    12 LEO Pharma Investigational Site Baton Rouge Louisiana United States 70808
    13 LEO Pharma Investigational Site Ann Arbor Michigan United States 48103
    14 LEO Pharma Investigational Site Ypsilanti Michigan United States 48197
    15 LEO Pharma Investigational Site Minneapolis Minnesota United States 55402
    16 LEO Pharma Investigational Site East Windsor New Jersey United States 08520
    17 LEO Pharma Investigational Site Corning New York United States 14830
    18 Leo Pharma Investigational Site New York New York United States 10075
    19 LEO Pharma Investigational Site High Point North Carolina United States 27262
    20 LEO Pharma Investigational Site Bexley Ohio United States 43209
    21 Leo Pharma Investigational Site Tulsa Oklahoma United States 74136
    22 LEO Pharma Investigational Site Portland Oregon United States 97223
    23 LEO Pharma Investigational Site Portland Oregon United States 97239
    24 LEO Pharma Investigational Site Philadelphia Pennsylvania United States 19104
    25 Leo Pharma Investigational Site North Charleston South Carolina United States 29420
    26 Leo Pharma Investigational Site Murfreesboro Tennessee United States 37130
    27 LEO Pharma Investigational Site Austin Texas United States 78746
    28 LEO Pharma Investigational Site Houston Texas United States 77030
    29 Leo Pharma Investigational Site San Antonio Texas United States 78218
    30 Leo Pharma Investigationel Site Darlinghurst Australia 2010
    31 Leo Pharma Investigationel Site Kogarah Australia 2217
    32 Leo Pharma Investigationel Site Melbourne Australia 3002
    33 Leo Pharma Investigationel Site Woolloongabba Australia 4102
    34 Leo Pharma Investigationel Site Brussels Belgium 1200
    35 Leo Pharma Investigationel Site Gent Belgium B-9000
    36 Leo Pharma Investigationel Site Liège Belgium 4000
    37 Leo Pharma Investigational Site Maldegem Belgium 9990
    38 LEO Pharma Investigational Site Calgary Alberta Canada T3A 2N1
    39 LEO Pharma Investigational Site Edmonton Alberta Canada T6G 1C9
    40 LEO Pharma Investigational Site Surrey British Columbia Canada V3R 6A7
    41 LEO Pharma Investigational Site Winnipeg Manitoba Canada R3C 1T6
    42 LEO Pharma Investigational Site Winnipeg Manitoba Canada R3M 3Z4
    43 LEO Pharma Investigational Site Markham Ontario Canada L3P 1X2
    44 LEO Pharma Investigational Site Oakville Ontario Canada L6J 7W5
    45 LEO Pharma Investigational Site Toronto Ontario Canada M5A 3R6
    46 LEO Pharma Investigational Site Windsor Ontario Canada N8X 2G1
    47 LEO Pharma Investigational Site Montreal Quebec Canada H3T 1C5
    48 LEO Pharma Investigational Site Saskatoon Saskatchewan Canada S7K 0H6
    49 Leo Pharma Investigationel Site Marseille France 13285
    50 Leo Pharma Investigationel Site Nice France 06200
    51 Leo Pharma Investigationel Site Paris France 75015
    52 Leo Pharma Investigationel Site Paris France 75020
    53 Leo Pharma Investigationel Site Valence France 26000
    54 Leo Pharma Investigationel Site Berlin Germany 10115
    55 Leo Pharma Investigationel Site Dresden Germany 01307
    56 Leo Pharma Investigationel Site Jena Germany 49074
    57 Leo Pharma Investigationel Site Osnabrück Germany 49074
    58 Leo Pharma Investigationel Site Fukuoka Japan 814-0180
    59 Leo Pharma Investigationel Site Kagoshima city Japan 890-8520
    60 Leo Pharma Investigationel Site Kyoto Japan 602-8566
    61 Leo Pharma Investigationel Site Nagoya-shi Japan 457-8510
    62 Leo Pharma Investigationel Site Obihiro Japan 080-0013
    63 Leo Pharma Investigationel Site Osaka-fu Japan 560-0085
    64 Leo Pharma Investigationel Site Osaka Japan 593-8324
    65 Leo Pharma Investigationel Site Shimotsuke Japan 329-0498
    66 Leo Pharma Investigationel Site Tokyo Japan 136-0074
    67 Leo Pharma Investigationel Site Tokyo Japan 141-8625
    68 Leo Pharma Investigationel Site Tokyo Japan 169-0075
    69 Leo Pharma Investigationel Site Tokyo Japan 171-0022
    70 Leo Pharma Investigationel Site Tsu Japan 514-8507
    71 Leo Pharma Investigationel Site Yamanashi Japan 400-8506
    72 Leo Pharma Investigationel Site Bergen Op Zoom Netherlands 4708
    73 Leo Pharma Investigationel Site Breda Netherlands 4818
    74 Leo Pharma Investigationel Site Groningen Netherlands 9713
    75 Leo Pharma Investigationel Site Rotterdam Netherlands 3015
    76 Leo Pharma Investigationel Site Kraków Poland 30-033
    77 Leo Pharma Investigationel Site Kraków Poland 30-149
    78 Leo Pharma Investigationel Site Kraków Poland 31-011
    79 Leo Pharma Investigationel Site Rzeszów Poland 35-055
    80 Leo Pharma Investigationel Site Swidnik Poland 21-040
    81 Leo Pharma Investigationel Site Wrocław Poland 50-001
    82 Leo Pharma Investigationel Site Wrocław Poland 51-318
    83 Leo Pharma Investigationel Site Wrocław Poland 52-416
    84 Leo Pharma Investigationel Site Łódź Poland 90-265
    85 Leo Pharma Investigationel Site Łódź Poland 90-436
    86 Leo Pharma Investigationel Site Glasgow United Kingdom G51 4TF
    87 Leo Pharma Investigationel Site London United Kingdom E11 1NR

    Sponsors and Collaborators

    • LEO Pharma

    Investigators

    • Study Director: Medical expert, LEO Pharma

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    LEO Pharma
    ClinicalTrials.gov Identifier:
    NCT03526861
    Other Study ID Numbers:
    • LP0162-1334
    • 2017-005143-33
    First Posted:
    May 16, 2018
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022
    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

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo Maintenance Treatment Period - Tralokinumab 300 mg Q2W Maintenance Treatment Period - Tralokinumab 300 mg Q4W Maintenance Treatment Period - Tralokinumab 150 mg Q2W Maintenance Treatment Period - Tralokinumab 150 mg Q4W Maintenance Treatment Period - Placebo Q2W Open-label Treatment -Tralokinumab 300 mg Q2W + Optional TCS
    Arm/Group 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. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to placebo, assigned to continue to placebo Q2W. At each visit (Q2W), subject received 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects receiving initial treatment with tralokinumab 150 mg/tralokinumab 300 mg/placebo Q2W who did not achieve clinical response at Week 16 without use of rescue medication from Week 2 to Week 16, 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 150 mg Q2W/Q4W, 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. 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. Not achieving EASI75 over at least a 4-week period (over 3 consecutive visits) for subjects with IGA>1 at Week 16. At each visit, subjects received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab Q2W to receive a total dose of 300 mg.
    Period Title: Initial Treatment Period
    STARTED 101 100 100 0 0 0 0 0 0
    COMPLETED 94 93 86 0 0 0 0 0 0
    NOT COMPLETED 7 7 14 0 0 0 0 0 0
    Period Title: Initial Treatment Period
    STARTED 0 0 0 13 14 12 14 6 0
    COMPLETED 0 0 0 5 8 8 8 4 0
    NOT COMPLETED 0 0 0 8 6 4 6 2 0
    Period Title: Initial Treatment Period
    STARTED 0 0 0 0 0 0 0 0 242
    COMPLETED 0 0 0 0 0 0 0 0 214
    NOT COMPLETED 0 0 0 0 0 0 0 0 28

    Baseline Characteristics

    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo Total
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo. Total of all reporting groups
    Overall Participants 101 100 100 301
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    14.6
    (1.8)
    14.8
    (1.7)
    14.4
    (1.6)
    14.6
    (1.7)
    Sex: Female, Male (Count of Participants)
    Female
    52
    51.5%
    48
    48%
    46
    46%
    146
    48.5%
    Male
    49
    48.5%
    52
    52%
    54
    54%
    155
    51.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    12
    11.9%
    10
    10%
    10
    10%
    32
    10.6%
    Not Hispanic or Latino
    89
    88.1%
    90
    90%
    90
    90%
    269
    89.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    59
    58.4%
    56
    56%
    58
    58%
    173
    57.5%
    Black or African American
    14
    13.9%
    8
    8%
    12
    12%
    34
    11.3%
    Asian
    21
    20.8%
    28
    28%
    23
    23%
    72
    23.9%
    American Indian or Alaska Native
    0
    0%
    2
    2%
    1
    1%
    3
    1%
    Native Hawaiian or Other Pacific Islander
    2
    2%
    0
    0%
    2
    2%
    4
    1.3%
    Other
    5
    5%
    6
    6%
    4
    4%
    15
    5%
    Region of Enrollment (participants) [Number]
    Canada
    21
    20.8%
    19
    19%
    12
    12%
    52
    17.3%
    Netherlands
    4
    4%
    4
    4%
    5
    5%
    13
    4.3%
    Belgium
    2
    2%
    3
    3%
    3
    3%
    8
    2.7%
    United States
    31
    30.7%
    33
    33%
    41
    41%
    105
    34.9%
    Japan
    11
    10.9%
    10
    10%
    11
    11%
    32
    10.6%
    Poland
    19
    18.8%
    20
    20%
    15
    15%
    54
    17.9%
    United Kingdom
    1
    1%
    0
    0%
    3
    3%
    4
    1.3%
    Australia
    5
    5%
    5
    5%
    4
    4%
    14
    4.7%
    France
    2
    2%
    2
    2%
    4
    4%
    8
    2.7%
    Germany
    5
    5%
    4
    4%
    2
    2%
    11
    3.7%
    Investigator's Global Assessment (Count of Participants)
    Clear
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Almost Clear
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Mild
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Moderate
    52
    51.5%
    55
    55%
    54
    54%
    161
    53.5%
    Severe
    48
    47.5%
    44
    44%
    45
    45%
    137
    45.5%
    Missing
    1
    1%
    1
    1%
    1
    1%
    3
    1%
    Eczema Area and Severity Index (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    31.90
    (13.74)
    31.89
    (12.97)
    31.25
    (14.19)
    31.68
    (13.60)
    Scoring Atopic Dermatitis (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    68.41
    (13.51)
    67.42
    (14.51)
    67.70
    (14.77)
    67.84
    (14.23)
    Children's Dermatology Life Quality Index (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    13.29
    (7.18)
    12.86
    (6.27)
    13.14
    (5.99)
    13.10
    (6.48)
    Adolescent Worst Pruritus NRS (weekly average) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    7.79
    (1.53)
    7.49
    (1.58)
    7.45
    (1.62)
    7.58
    (1.58)
    Body surface area affected by atopic dermatitis (AD) (percentage affected) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage affected]
    49.8
    (23.0)
    52.0
    (22.5)
    50.9
    (23.5)
    50.9
    (23.0)
    Age of onset of atopic dermatitis (AD) (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    2.5
    (3.5)
    2.1
    (3.3)
    2.4
    (3.5)
    2.4
    (3.4)
    Duration of atopic dermatitis (AD) (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    12.1
    (3.7)
    12.7
    (3.7)
    12.0
    (3.4)
    12.3
    (3.6)

    Outcome Measures

    1. Primary Outcome
    Title Subjects 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 AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    17
    16.8%
    21
    21%
    4
    4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects with IGA score of 0 (clear) or 1 (almost clear) at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments Primary endpoint tested sequentially at a 5% significance level
    Statistical Test of Hypothesis p-Value 0.002
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 13.8
    Confidence Interval (2-Sided) 95%
    5.3 to 22.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and baseline disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects with IGA score of 0 (clear) or 1 (almost clear) at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments Primary endpoint tested sequentially at a 5% significance level
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 17.5
    Confidence Interval (2-Sided) 95%
    8.4 to 26.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and baseline disease severity.
    2. Primary Outcome
    Title Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16
    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.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    27
    26.7%
    28
    28%
    6
    6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 75% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments Primary endpoint tested sequentially at a 5% significance level
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 22.0
    Confidence Interval (2-Sided) 95%
    12.0 to 32.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and baseline disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 75% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments Primary endpoint tested sequentially at a 5% significance level
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 22.5
    Confidence Interval (2-Sided) 95%
    12.4 to 32.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and baseline disease severity.
    3. Secondary Outcome
    Title Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16
    Description The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set with baseline Adolescent Worst Pruritus weekly average ≥4. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 96 95 90
    Count of Participants [Participants]
    24
    23.8%
    22
    22%
    3
    3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects with at least 4-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments Secondary endpoint tested sequentially at a 2.5% significance level
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 21.7
    Confidence Interval (2-Sided) 95%
    12.3 to 31.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and baseline disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects with at least 4-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments Secondary endpoint tested sequentially at a 5% significance level
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 19.9
    Confidence Interval (2-Sided) 95%
    10.6 to 29.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and baseline disease severity.
    4. Secondary Outcome
    Title Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16
    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.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Least Squares Mean (Standard Error) [units on a scale]
    -29.1
    (2.4)
    -27.5
    (2.4)
    -9.5
    (3.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments This secondary endpoint was tested sequentially using the Holm-Bonferroni method for multiplicity adjustment at a 2.5% significance level after the sequential testing of the primary endpoints and first secondary endpoint, if these showed statistical significance.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -19.7
    Confidence Interval (2-Sided) 95%
    -27.1 to -12.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments This secondary endpoint was tested sequentially using the Holm-Bonferroni method for multiplicity adjustment at a 5% significance level after the sequential testing of the primary endpoints and first secondary endpoint, if these showed statistical significance.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -18.0
    Confidence Interval (2-Sided) 95%
    -25.6 to -10.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16
    Description The CDLQI 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 various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point Likert scale (0 = 'not at all'; 1 = 'only a little'; 2 = 'quite a lot'; 3 = 'very much'). Item 7 (on school time) has one additional response category 'prevented school', which is also scored '3'. The total score of the CDLQI is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set with non-missing baseline CDLQI score. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 94 95 89
    Least Squares Mean (Standard Error) [units on a scale]
    -6.7
    (0.6)
    -6.1
    (0.6)
    -4.1
    (0.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments This secondary endpoint was tested sequentially using the Holm-Bonferroni method for multiplicity adjustment at a 2.5% significance level after the sequential testing of the primary endpoints and first secondary endpoint, if these showed statistical significance.
    Statistical Test of Hypothesis p-Value 0.007
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -2.6
    Confidence Interval (2-Sided) 95%
    -4.5 to -0.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments This secondary endpoint was tested sequentially using the Holm-Bonferroni method for multiplicity adjustment at a 5% significance level after the sequential testing of the primary endpoints and first secondary endpoint, if these showed statistical significance.
    Statistical Test of Hypothesis p-Value 0.040
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -2.0
    Confidence Interval (2-Sided) 95%
    -3.9 to -0.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Number of Adverse Events
    Description Number of AEs during the Initial treatment period is presented. For a summary of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the initial treatment period, maintenance treatment period, open-label treatment period, and safety follow-up period, see the Adverse Events Overview section.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on the safety analysis set. The safety analysis set comprised all subjects randomised to initial treatment and exposed to IMP, except for subjects randomised at the investigational sites where substantial quality/GCP issues were identified . The safety analysis set was identical to the full analysis set.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Number [number of adverse events]
    130
    175
    134
    7. Secondary Outcome
    Title Presence of Anti-drug Antibodies
    Description Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    The analysis was performed on the safety analysis set. The safety analysis set comprised all subjects randomised to initial treatment, except for subjects randomised at the investigational sites where substantial quality/GCP issues were identified and subjects for whom no post-baseline safety data were available. The safety analysis set was identical to the full analysis set.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    1
    1%
    7
    7%
    2
    2%
    8. Secondary Outcome
    Title Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16.
    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.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    50
    49.5%
    45
    45%
    13
    13%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 50% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 38.5
    Confidence Interval (2-Sided) 95%
    26.8 to 50.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 50% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 32.4
    Confidence Interval (2-Sided) 95%
    20.6 to 44.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    9. Secondary Outcome
    Title Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16.
    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.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    17
    16.8%
    19
    19%
    4
    4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 90% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value 0.002
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 13.7
    Confidence Interval (2-Sided) 95%
    5.2 to 22.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 90% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 15.3
    Confidence Interval (2-Sided) 95%
    6.5 to 24.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    10. Secondary Outcome
    Title Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16
    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.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Least Squares Mean (Standard Error) [units on a scale]
    -18.1
    (1.3)
    -18.1
    (1.4)
    -8.7
    (1.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -9.4
    Confidence Interval (2-Sided) 95%
    -13.5 to -5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -9.4
    Confidence Interval (2-Sided) 95%
    -13.6 to -5.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16
    Description The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    12
    11.9%
    16
    16%
    1
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 75% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value 0.002
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 11.5
    Confidence Interval (2-Sided) 95%
    4.5 to 18.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 75% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 15.6
    Confidence Interval (2-Sided) 95%
    7.8 to 23.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    12. Secondary Outcome
    Title Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16
    Description The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 97 98 94
    Count of Participants [Participants]
    30
    29.7%
    30
    30%
    5
    5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 50% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 26.2
    Confidence Interval (2-Sided) 95%
    16.1 to 36.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects who achieved at least 50% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 25.5
    Confidence Interval (2-Sided) 95%
    15.3 to 35.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    13. Secondary Outcome
    Title Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16
    Description The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set with non-missing baseline Adolescent Worst Pruritus NRS score. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 96 96 92
    Least Squares Mean (Standard Error) [units on a scale]
    -3.0
    (0.3)
    -2.7
    (0.3)
    -1.5
    (0.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -1.5
    Confidence Interval (2-Sided) 95%
    -2.4 to -0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value 0.007
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -1.2
    Confidence Interval (2-Sided) 95%
    -2.1 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. Secondary Outcome
    Title Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16
    Description The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set with baseline Adolescent Worst Pruritus weekly average ≥3. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 96 95 91
    Count of Participants [Participants]
    28
    27.7%
    29
    29%
    8
    8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects with at least 3-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 20.3
    Confidence Interval (2-Sided) 95%
    9.7 to 31.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments Subjects with at least 3-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'composite'.
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 21.8
    Confidence Interval (2-Sided) 95%
    10.9 to 32.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Mantel-Haenszel risk difference, stratified by region and disease severity.
    15. Secondary Outcome
    Title Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16
    Description The POEM is a validated questionnaire used to assess disease symptoms in atopic eczema patients in both clinical practice and clinical trials. The tool consists of 7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness). Subjects will score how often they have experienced each symptom over the previous week on a 5-point categorical response scale (0 = 'no days'; 1 = '1 to 2 days'; 2 = '3 to 4 days'; 3 = '5 to 6' days; 4 = 'every day'). The total score is the sum of the 7 items (range 0 to 28) and reflects disease-related morbidity; a high score is indicative of a worse disease severity.
    Time Frame From Week 0 to Week 16

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set with non-missing baseline POEM score. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W Initial Treatment Period - Placebo
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 0 to Week 16: Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 94 95 87
    Least Squares Mean (Standard Error) [units on a scale]
    -8.4
    (0.8)
    -7.8
    (0.8)
    -2.4
    (1.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 300 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -6.0
    Confidence Interval (2-Sided) 95%
    -8.4 to -3.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Initial Treatment Period - Tralokinumab 150 mg Q2W, Initial Treatment Period - Placebo
    Comments 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. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.
    Type of Statistical Test Superiority
    Comments The statistical test was not controlled for multiplicity.
    Statistical Test of Hypothesis p-Value <0.001
    Comments Based on the primary analysis of the primary estimand 'hypothetical'.
    Method Repeated measurements model
    Comments
    Method of Estimation Estimation Parameter Difference of least square means
    Estimated Value -5.4
    Confidence Interval (2-Sided) 95%
    -7.9 to -3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Tralokinumab Serum Trough Concentration at Week 16
    Description Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.
    Time Frame At Week 16

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set who were randomised to tralokinumab. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 mg Q2W Initial Treatment Period - Tralokinumab 150 mg Q2W
    Arm/Group 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 subcutaneous administration. At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 0 to Week 16: Tralokinumab 150 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 subcutaneous administration. At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab.
    Measure Participants 97 98
    Geometric Mean (Geometric Coefficient of Variation) [microgram/mL]
    105.7
    (39.0)
    56.4
    (35.4)
    17. Secondary Outcome
    Title Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16
    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).
    Time Frame At Week 52

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set (FAS) who were re-randomised to maintenance treatment and achieved an Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 without use of rescue medication from Week 2 to Week 16.
    Arm/Group Title Maintenance Treatment Period - Tralokinumab 300 mg Q2W Maintenance Treatment Period - Tralokinumab 300 mg Q4W Maintenance Treatment Period - Tralokinumab 150 mg Q2W Maintenance Treatment Period - Tralokinumab 150 mg Q4W
    Arm/Group Description Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 2 subcutaneous injection (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 8 8 9 10
    Count of Participants [Participants]
    3
    3%
    7
    7%
    6
    6%
    6
    2%
    18. Secondary Outcome
    Title Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16
    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.
    Time Frame At Week 52

    Outcome Measure Data

    Analysis Population Description
    Subjects in the full analysis set (FAS) who were re-randomised to maintenance treatment and achieved at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 without use of rescue medication from Week 2 to Week 16.
    Arm/Group Title Maintenance Treatment Period - Tralokinumab 300 mg Q2W Maintenance Treatment Period - Tralokinumab 300 mg Q4W Maintenance Treatment Period - Tralokinumab 150 mg Q2W Maintenance Treatment Period - Tralokinumab 150 mg Q4W
    Arm/Group Description Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 2 subcutaneous injection (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo.
    Measure Participants 9 13 11 14
    Count of Participants [Participants]
    4
    4%
    7
    7%
    7
    7%
    7
    2.3%
    19. Secondary Outcome
    Title Tralokinumab Serum Trough Concentration at Week 66
    Description Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.
    Time Frame At Week 66

    Outcome Measure Data

    Analysis Population Description
    13 subjects in maintenance safety analysis set who were initially randomised to tralokinumab and completed the maintenance treatment period on treatment. 234 subjects in the open-label safety analysis set.
    Arm/Group Title Maintenance Treatment Period - Tralokinumab 300 mg Q2W Maintenance Treatment Period - Tralokinumab 300 mg Q4W Maintenance Treatment Period - Tralokinumab 150 mg Q2W Maintenance Treatment Period - Tralokinumab 150 mg Q4W Open-label Treatment -Tralokinumab 300 mg Q2W + Optional TCS
    Arm/Group Description Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 300 mg Q2W, re-randomised to tralokinumab 300 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 2 subcutaneous injection (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q2W maintenance dosing regimen. At each visit (Q2W), subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. Week 16 to Week 52: Subjects achieving a clinical response at Week 16 without use of rescue medication from Week 2 to Week 16 from Week 2 to Week 16 and initially randomised to tralokinumab 150 mg Q2W, re-randomised to tralokinumab 150 mg Q4W maintenance dosing regimen. At each visit (Q2W), subject received alternating dose administrations: 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab; or 2 subcutaneous injections (each 1.0 mL) of placebo. Week 16 to Week 52: Subjects receiving initial treatment with tralokinumab 150 mg/tralokinumab 300 mg/placebo Q2W who did not achieve clinical response at Week 16 without use of rescue medication from Week 2 to Week 16, 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 150 mg Q2W/Q4W, 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. 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. Not achieving EASI75 over at least a 4-week period (over 3 consecutive visits) for subjects with IGA>1 at Week 16. At each visit, subjects received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab Q2W to receive a total dose of 300 mg.
    Measure Participants 1 5 4 3 234
    Geometric Mean (Geometric Coefficient of Variation) [microgram/mL]
    5.9
    (NA)
    1.0
    (458.0)
    1.5
    (168.6)
    2.6
    (75.6)
    4.4
    (136.5)

    Adverse Events

    Time Frame Initial Treatment Period: Week 0 to Week 16, Maintenance Treatment Period: Week 16 to Week 52, Open-label Treatment: Week 16 to Week 52; Safety Follow-up Period: Week 52 to Week 66.
    Adverse Event Reporting Description
    Arm/Group Title Initial Treatment Period - Tralokinumab 300 Q2W Initial Treatment Period - Tralokinumab 150 Q2W Initial Treatment Period - Placebo Maintenance Treatment Period - Tralokinumab 300 Q2W Maintenance Treatment Period - Tralokinumab 300 Q4W Maintenance Treatment Period - Tralokinumab 150 Q2W Maintenance Treatment Period - Tralokinumab 150 Q4W Maintenance Treatment Period - Placebo Open-label Treatment - Tralokinumab 300 Q2W + Optional TCS Safety Follow-up
    Arm/Group Description Initial Treatment Period - Tralokinumab 300 Q2W (n=97, PYE=29.48) Initial Treatment Period - Tralokinumab 150 Q2W (n=98, PYE=29.33) Initial Treatment Period - Placebo (n=94, PYE=27.93) Maintenance Treatment Period - Tralokinumab 300 Q2W (n=11, PYE=5.61) Maintenance Treatment Period - Tralokinumab 300 Q4W (n=13, PYE=6.78) Maintenance Treatment Period - Tralokinumab 150 Q2W (n=12, PYE=6.40) Maintenance Treatment Period - Tralokinumab 150 Q4W (n=14, PYE=6.53) Maintenance Treatment Period - Placebo (n=6, PYE=2.98) Open-label Treatment - Tralokinumab 300 Q2W + optional TCS (n=234, PYE=151.12) Safety Follow-up (n=234, PYE=54.00)
    All Cause Mortality
    Initial Treatment Period - Tralokinumab 300 Q2W Initial Treatment Period - Tralokinumab 150 Q2W Initial Treatment Period - Placebo Maintenance Treatment Period - Tralokinumab 300 Q2W Maintenance Treatment Period - Tralokinumab 300 Q4W Maintenance Treatment Period - Tralokinumab 150 Q2W Maintenance Treatment Period - Tralokinumab 150 Q4W Maintenance Treatment Period - Placebo Open-label Treatment - Tralokinumab 300 Q2W + Optional TCS Safety Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/97 (0%) 0/98 (0%) 0/94 (0%) 0/11 (0%) 0/13 (0%) 0/12 (0%) 0/14 (0%) 0/6 (0%) 0/234 (0%) 0/234 (0%)
    Serious Adverse Events
    Initial Treatment Period - Tralokinumab 300 Q2W Initial Treatment Period - Tralokinumab 150 Q2W Initial Treatment Period - Placebo Maintenance Treatment Period - Tralokinumab 300 Q2W Maintenance Treatment Period - Tralokinumab 300 Q4W Maintenance Treatment Period - Tralokinumab 150 Q2W Maintenance Treatment Period - Tralokinumab 150 Q4W Maintenance Treatment Period - Placebo Open-label Treatment - Tralokinumab 300 Q2W + Optional TCS Safety Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/97 (1%) 3/98 (3.1%) 5/94 (5.3%) 0/11 (0%) 0/13 (0%) 0/12 (0%) 0/14 (0%) 0/6 (0%) 7/234 (3%) 3/234 (1.3%)
    Gastrointestinal disorders
    Gastritis 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Immune system disorders
    Anaphylactic reaction 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 1/234 (0.4%) 1
    Infections and infestations
    Appendicitis perforated 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Cellulitis 0/97 (0%) 0 1/98 (1%) 1 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Infectious mononucleosis 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Injury, poisoning and procedural complications
    Concussion 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Intentional overdose 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 1/234 (0.4%) 1
    Radius fracture 1/97 (1%) 1 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Nervous system disorders
    Cerebrovascular accident 0/97 (0%) 0 1/98 (1%) 1 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Psychiatric disorders
    Anorexia nervosa 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Obsessive-compulsive disorder 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Suicidal ideation 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Renal and urinary disorders
    Renal injury 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 1/234 (0.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Asthma 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic 0/97 (0%) 0 1/98 (1%) 1 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Other (Not Including Serious) Adverse Events
    Initial Treatment Period - Tralokinumab 300 Q2W Initial Treatment Period - Tralokinumab 150 Q2W Initial Treatment Period - Placebo Maintenance Treatment Period - Tralokinumab 300 Q2W Maintenance Treatment Period - Tralokinumab 300 Q4W Maintenance Treatment Period - Tralokinumab 150 Q2W Maintenance Treatment Period - Tralokinumab 150 Q4W Maintenance Treatment Period - Placebo Open-label Treatment - Tralokinumab 300 Q2W + Optional TCS Safety Follow-up
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 44/97 (45.4%) 47/98 (48%) 36/94 (38.3%) 7/11 (63.6%) 6/13 (46.2%) 7/12 (58.3%) 8/14 (57.1%) 4/6 (66.7%) 100/234 (42.7%) 16/234 (6.8%)
    Endocrine disorders
    Adrenal insufficiency 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Eye disorders
    Cataract 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Conjunctivitis allergic 2/97 (2.1%) 2 2/98 (2%) 2 2/94 (2.1%) 3 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 1 1/14 (7.1%) 1 0/6 (0%) 0 4/234 (1.7%) 4 0/234 (0%) 0
    General disorders
    Fatigue 0/97 (0%) 0 4/98 (4.1%) 4 4/94 (4.3%) 4 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Injection site reaction 2/97 (2.1%) 3 6/98 (6.1%) 9 0/94 (0%) 0 0/11 (0%) 0 1/13 (7.7%) 1 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 10/234 (4.3%) 16 0/234 (0%) 0
    Malaise 0/97 (0%) 0 1/98 (1%) 2 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 6 0/14 (0%) 0 0/6 (0%) 0 2/234 (0.9%) 12 0/234 (0%) 0
    Immune system disorders
    Hypersensitivity 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Infections and infestations
    Acute sinusitis 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 2 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Bacterial vaginosis 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 1/13 (7.7%) 1 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Conjunctivitis 0/97 (0%) 0 2/98 (2%) 2 0/94 (0%) 0 0/11 (0%) 0 1/13 (7.7%) 1 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 4/234 (1.7%) 6 2/234 (0.9%) 2
    Furuncle 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/234 (0%) 0 0/234 (0%) 0
    Herpes zoster 0/97 (0%) 0 1/98 (1%) 1 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 1/234 (0.4%) 1 0/234 (0%) 0
    Infectious mononucleosis 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 1 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Influenza 2/97 (2.1%) 2 2/98 (2%) 2 1/94 (1.1%) 1 2/11 (18.2%) 2 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 3/234 (1.3%) 3 2/234 (0.9%) 2
    Oral herpes 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 6/234 (2.6%) 7 0/234 (0%) 0
    Pharyngitis 0/97 (0%) 0 2/98 (2%) 2 4/94 (4.3%) 4 0/11 (0%) 0 0/13 (0%) 0 3/12 (25%) 4 0/14 (0%) 0 0/6 (0%) 0 6/234 (2.6%) 6 1/234 (0.4%) 1
    Upper respiratory tract infection 11/97 (11.3%) 11 8/98 (8.2%) 10 4/94 (4.3%) 5 2/11 (18.2%) 2 0/13 (0%) 0 1/12 (8.3%) 2 1/14 (7.1%) 1 0/6 (0%) 0 25/234 (10.7%) 34 3/234 (1.3%) 3
    Viral upper respiratory tract infection 12/97 (12.4%) 16 19/98 (19.4%) 22 8/94 (8.5%) 10 2/11 (18.2%) 2 1/13 (7.7%) 1 1/12 (8.3%) 2 1/14 (7.1%) 1 0/6 (0%) 0 44/234 (18.8%) 60 1/234 (0.4%) 2
    Injury, poisoning and procedural complications
    Inappropriate schedule of drug administration 0/97 (0%) 0 1/98 (1%) 1 0/94 (0%) 0 0/11 (0%) 0 1/13 (7.7%) 1 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 2/234 (0.9%) 2 0/234 (0%) 0
    Procedural anxiety 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Wrong drug administered 1/97 (1%) 1 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 1/6 (16.7%) 1 0/234 (0%) 0 0/234 (0%) 0
    Musculoskeletal and connective tissue disorders
    Bursitis 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0
    Nervous system disorders
    Headache 6/97 (6.2%) 6 5/98 (5.1%) 5 3/94 (3.2%) 3 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 12/234 (5.1%) 17 0/234 (0%) 0
    Migraine 0/97 (0%) 0 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 2/234 (0.9%) 2 0/234 (0%) 0
    Psychiatric disorders
    Abnormal behaviour 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 1/11 (9.1%) 1 0/13 (0%) 0 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Attention deficit/hyperactivity disorder 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 0/12 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain 4/97 (4.1%) 4 1/98 (1%) 2 3/94 (3.2%) 3 0/11 (0%) 0 1/13 (7.7%) 1 0/12 (0%) 0 1/14 (7.1%) 1 0/6 (0%) 0 4/234 (1.7%) 4 0/234 (0%) 0
    Rhinorrhoea 1/97 (1%) 1 0/98 (0%) 0 1/94 (1.1%) 1 0/11 (0%) 0 1/13 (7.7%) 1 0/12 (0%) 0 0/14 (0%) 0 0/6 (0%) 0 2/234 (0.9%) 2 0/234 (0%) 0
    Skin and subcutaneous tissue disorders
    Acne 3/97 (3.1%) 3 0/98 (0%) 0 4/94 (4.3%) 4 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 1 1/14 (7.1%) 1 0/6 (0%) 0 3/234 (1.3%) 3 1/234 (0.4%) 1
    Dermatitis allergic 0/97 (0%) 0 0/98 (0%) 0 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 1 0/14 (0%) 0 0/6 (0%) 0 0/234 (0%) 0 0/234 (0%) 0
    Dermatitis atopic 7/97 (7.2%) 7 12/98 (12.2%) 16 11/94 (11.7%) 15 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 1 2/14 (14.3%) 2 1/6 (16.7%) 1 19/234 (8.1%) 26 8/234 (3.4%) 9
    Dermatitis contact 0/97 (0%) 0 1/98 (1%) 1 0/94 (0%) 0 0/11 (0%) 0 0/13 (0%) 0 1/12 (8.3%) 1 0/14 (0%) 0 0/6 (0%) 0 1/234 (0.4%) 1 0/234 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    LEO Pharma seeks publication of all Phase 3 clinical trials in peer-reviewed journals within 18 months of trial completion, regardless of whether the findings are positive or negative. If there is no multi-centre publication within 18 months after the clinical trial has been completed or terminated at all trial sites, the investigator has the right to publish the results from the clinical trial generated by the investigator.

    Results Point of Contact

    Name/Title Disclosure Specialist
    Organization LEO Pharma A/S
    Phone +45 44945888
    Email disclosure@leo-pharma.com
    Responsible Party:
    LEO Pharma
    ClinicalTrials.gov Identifier:
    NCT03526861
    Other Study ID Numbers:
    • LP0162-1334
    • 2017-005143-33
    First Posted:
    May 16, 2018
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022