Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis - ECZTRA 2 (ECZema TRAlokinumab Trial no. 2) (ECZTRA 2)

A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Tralokinumab Monotherapy in Subjects With Moderate to Severe Atopic Dermatitis Who Are Candidates for Systemic Therapy

Primary objective:

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

Maintenance objective:

To evaluate maintenance of effect with continued tralokinumab dosing up to 52 weeks compared to placebo for subjects achieving clinical response at Week 16.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Tralokinumab; Drug: Placebo

Detailed Description

Subjects found eligible following the screening period were randomized 3:1 to initial treatment with tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Randomization was stratified by region (Asia, Australia, Europe, and North America) and disease severity (Investigator's Global Assessment [IGA] 3 or 4).

Subjects achieving a clinical response at Week 16 (defined as IGA of 0 or 1 on a 5-point scale ranging from 0 [clear] to 4 [severe], or at least 75% reduction in Eczema Area and Severity Index [EASI] score from baseline [EASI75]) continued into maintenance treatment that continued until Week 52.

Subjects randomized to tralokinumab in the initial treatment period and who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) were re-randomized 2:2:1 to one of the following Q2W maintenance regimens stratified by region (Asia, Australia, Europe, and North America) and IGA response at Week 16 (IGA 0/1 or IGA >1):

• Tralokinumab 300 mg Q2W.
• Tralokinumab 300 mg Q4W (alternating dose administrations tralokinumab 300 mg and placebo).
• Placebo.

Subjects randomized to placebo in the initial treatment period who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) continued to receive placebo Q2W in the maintenance treatment period.

Subjects not achieving a clinical response at Week 16 as well as those who met the criteria listed below during maintenance treatment were transferred to open-label tralokinumab 300 mg Q2W treatment with optional use of topical corticosteroid (TCS) up to Week 52.

Transfer to open-label treatment during maintenance:

Subjects with IGA=0 at Week 16: IGA of at least 2 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects with IGA=1 at Week 16: IGA of at least 3 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects with IGA >1 at Week 16: not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects transferring to open-label treatment had the option to self-administer tralokinumab in their home after adequate training (at 3 dosing visits in the open-label period after additional consent has been obtained) by site staff at the investigator's discretion.

After completion of the maintenance treatment period (or open-label treatment), all subjects, except for those who entered the open-label long-term extension trial, continued in a 14-week off-treatment follow-up period for the assessment of safety and anti-drug antibody (ADA).

• Study Type: Interventional
• Enrollment (Actual): 794
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia, 2606
      • Woden Dermatology Pty Ltd.
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Skin & Cancer Foundation Australia
    • Kogarah, New South Wales, Australia, 2217
      • St. George Dermatology and Skin Cancer Center
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Veracity Clinical Research
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • Skin & Cancer Foundation Inc.
    • East Melbourne, Victoria, Australia, 3002
      • Sinclair Dermatology
  • Western Australia
    • Victoria Park, Western Australia, Australia, 6100
      • Burswood Dermatology
• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • Enverus Medical Research
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dr. Chih-ho Hong Medical
    • Vancouver, British Columbia, Canada, V6H 4E1
      • Pacific Derm
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • Winnipeg Clinic
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Wiseman Dermatology Research
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • Brunswick Dermatology Centre
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1A 5E8
      • Nexus Clinical Research
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B5H 1Z4
      • Eastern Canada Cutaneous Research
  • Ontario
    • Etobicoke, Ontario, Canada, M8X 1Y9
      • Kingsway Clinical Research
    • London, Ontario, Canada, N6A 3H7
      • Guenther Derm Research Centre
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research Inc.
    • Mississauga, Ontario, Canada, L5H 1G9
      • DermEdge Research
    • North Bay, Ontario, Canada, P1B 3Z7
      • Dermatology & Cosmetic Surgery
    • Ottawa, Ontario, Canada, K2G 6E2
      • Derm Clinic of Dr. Robern
    • Peterborough, Ontario, Canada, K9J 5K2
      • SKiN Centre for Dermatology
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • Dermatology & Cosmetic Surgery
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research
  • Quebec
    • Montréal, Quebec, Canada, H3H 1V4
      • Dr. David Gratton Dermatologue
    • Québec, Quebec, Canada, G1V 4X7
      • CRDQ
• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Hellerup, Denmark
    • Gentofte Hospital
  • Hellerup, Denmark
    • Bispebjerg Hospital
• Italy
  • Brescia, Italy, 25123
    • Spedali Civili Brescia
  • Catania, Italy, 95123
    • Policlinico-Vittorio Emanuele
  • L'Aquila, Italy, 67100
    • Opedale San Salvatore
  • Pisa, Italy, 56126
    • AOU Pisa
  • Rom, Italy, 00144
    • IRCCS San Gallicano
  • Rom, Italy, 00168
    • Policlinico "Agostino Gemelli"
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National Univeristy
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 425-707
    • Korea University Ansan Hospital
  • Gyeonggi-do, Korea, Republic of, 14584
    • Soon Chun Hyang University Hospital
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Incheon, Korea, Republic of, 21431
    • St. Mary's Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 06973
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of, 03722
    • Yonsei University Health Syste
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacr
• Poland
  • Gdynia, Poland, 81-338
    • Centrum Medyczne Gdynia
  • Gdynia, Poland, 81-384
    • Synexus Polska Gdyni
  • Katowice, Poland, 40-040
    • Synexus Polska Katowicach
  • Kraków, Poland, 31-501
    • Krakowskie Centrum Medyczne
  • Kraków, Poland, 30-002
    • Centrum Medyczne Pratia
  • Poznań, Poland, 60-702
    • Synexus Polska Poznaniu
  • Rzeszów, Poland, 35-055
    • Klinika Dermatologii
  • Łódź, Poland, 90-265
    • "DERMED" Centrum Medyczne Sp.
  • Łódź, Poland, 90-436
    • Dermoklinika Centrum Medyczne
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • Chelyabinsk Dermat. Dispensary
  • Moscow, Russian Federation, 107076
    • Federal State Budgetary Institution State Sci. Ctr.
  • Saint Petersburg, Russian Federation, 191123
    • French clinic of skin diseases
  • Saint Petersburg, Russian Federation, 194044
    • Military Medical Academy
• United Kingdom
  • Bury St Edmunds, United Kingdom, IP33 2QZ
    • West Suffolk Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, N19 5NF
    • The Whittington Hospital NHS
  • Angus
    • Dundee, Angus, United Kingdom, DD2 1GZ
      • Ninewells Hospital
  • Greater Manchester
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Salford Royal Hospital
  • London
    • Leytonstone, London, United Kingdom, E11 1NR
      • Whipps Cross University Hospital
  • North Yorkshire
    • Harrogate, North Yorkshire, United Kingdom, HG2 7SX
      • Harrogate District Hospital
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2RX
      • Royal Hallamshire Hospital
  • Surrey
    • Redhill, Surrey, United Kingdom, RH1 5RH
      • East Surrey Hospital
  • Tyne And Wear
    • Newcastle upon Tyne, Tyne And Wear, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Russells Hall Hospital
    • Walsall, West Midlands, United Kingdom, WS2 9PS
      • Walsall Healthcare NHS Trust
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS7 4SA
      • Chapel Allerton Hospital
• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
  • California
    • Encinitas, California, United States, 92024
      • California dermatology
    • Fullerton, California, United States, 92835
      • Advanced SkinCare Surgery & Med Center
    • Los Angeles, California, United States, 90033
      • USC Department of Dermatology
    • Murrieta, California, United States, 92562
      • Thiele Dermatology Specialists, Inc
    • Newport Beach, California, United States, 92660
      • Island Dermatology
    • San Diego, California, United States, 92123
      • Therapeutics Clinical Research
    • San Luis Obispo, California, United States, 93405
      • San Luis Dermatology and Laser Clinic
    • Santa Ana, California, United States, 92701
      • Southern California Dermatology, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Olympian Clinical Research
    • Miami, Florida, United States, 33176
      • Spotlight Research Center, LLC
    • North Miami Beach, Florida, United States, 33162
      • Private Practice - Dr. Tory P. Sullivan
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Marietta Dermatology Clinical Research, Inc.
    • Newnan, Georgia, United States, 30263
      • MedaPhase, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes-Fretzin Clinical Research Group, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Kansas City Dermatology, PA
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
      • Beacon Clinical Research
  • Michigan
    • Detroit, Michigan, United States, 48202
      • HFMC New Center One
    • Warren, Michigan, United States, 48088
      • The Grekin Skin Institute
    • Ypsilanti, Michigan, United States, 48197
      • Respiratory Medicine Research Institute of Michigan, PLC
  • Nevada
    • Henderson, Nevada, United States, 89074
      • Clinical Studies Group
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Psoriasis Treatment Center of Central New Jersey
  • New York
    • Corning, New York, United States, 14830
      • Corning Center for Clinical Research
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10075
      • Sadick Dermatology
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Health Physicians Office
    • Fairborn, Ohio, United States, 45324
      • Wright State Physicians
    • Westerville, Ohio, United States, 43082
      • Aventiv Research Inc.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Company, Inc.
    • Yardley, Pennsylvania, United States, 19067
      • Yardley Dermatology Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Clinical Research Center of the Carolinas
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Rivergate Dermatology Clinical Research Center
  • Texas
    • Bellaire, Texas, United States, 77401
      • Bellaire Dermatology Associates
    • Dallas, Texas, United States, 75231
      • Modern Research Associates, PLLC
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research, Inc.
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent and any locally required authorisation obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
2. Age 18 and above.
3. Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (33; Appendix 5).
4. Diagnosis of AD for ≥1 year.

5. Subjects who have a recent history (within 1 year before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., due to important side effects or safety risks).

   • Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0=clear to 2=mild) despite treatment with a daily regimen of TCS of medium to higher potency (±TCI as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super potent TCS), whichever is shorter.
   • Subjects with documented systemic treatment for AD in the past year are also considered as inadequate responders to topical treatments and are potentially eligible for treatment with tralokinumab after appropriate washout.
   • Important side effects or safety risks are those that outweigh the potential treatment benefits and include intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects, as assessed by the investigator or by the subject's treating physician.
6. AD involvement of ≥10% body surface area at screening and baseline (visit 3).
7. An EASI score of ≥12 at screening and 16 at baseline.
8. An IGA score of ≥3 at screening and at baseline.

9. A Worst Daily Pruritus numeric rating scale (NRS) average score of ≥4 during the week prior to baseline.

   • Worst Daily Pruritus NRS at baseline will be calculated from daily assessments of worst itch severity (Worst Daily Pruritus NRS) during the 7 days immediately preceding randomisation (Day 6 to 0). A minimum of 4 Worst Daily Pruritus NRS scores out of the 7 days is required to calculate the baseline average score. For subjects who do not have at least 4 scores reported during the 7 days immediately preceding the planned randomisation date, randomisation should be postponed until this requirement is met, but without exceeding the 6 weeks maximum duration for screening.

10. Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation (refer to exclusion criterion no. 8 for limitations regarding emollients).

11. Women of childbearing potential must use a highly effective* form of birth control (confirmed by the investigator) throughout the trial and at least for 16 weeks (5 half lives) after last administration of IMP.

    • A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year) such as bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), sexual abstinence (when this is in line with the preferred and usual life style of the subject), vasectomised partner (given that the subject is monogamous). The subjects must have used the contraceptive method continuously for at least 1 month prior to the pregnancy test at baseline. A female is defined as not being of child-bearing potential if she is postmenopausal (at least 12 months with no menses without an alternative medical cause prior to screening), or surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy).

Exclusion Criteria:

1. Concurrent enrolment in another clinical trial where the subject is receiving an IMP.
2. Previous randomisation in tralokinumab trials.
3. Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, or psoriasis.
4. Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
5. Use of tanning beds or phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), within 6 weeks prior to randomisation.

6. Treatment with the following medications within 4 weeks prior to randomisation:

   • Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, Janus kinase inhibitors etc.).
   • Systemic corticosteroid use (excludes topical, inhaled, or intranasal delivery).
   • Three or more bleach baths during any week within the 4 weeks.

7. Treatment with the following medications within 2 weeks prior to randomisation

   • TCS.
   • TCI.
   • Topical PDE 4 inhibitor.
8. Initiation of treatment of AD with prescription emollients or emollients containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (subjects may continue using stable doses of such emollients if initiated before the screening visit).

9. Receipt of live attenuated vaccines 30 days prior to the date of randomisation and during the trial including the safety follow-up period.

   • Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed, provided they are not administered within 5 days before/after any study visit.

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

    • Any cell-depleting agents including but not limited to rituximab: within 6 months prior to randomisation, or until lymphocyte count returns to normal, whichever is longer.
    • Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to randomisation.
11. Receipt of any investigational non-biologic agent within 5 half-lives prior to randomisation.
12. Receipt of blood products within 4 weeks prior to screening.
13. Major surgery within 8 weeks prior to screening, or planned in-patient surgery or hospitalisation during the trial period.
14. Known or suspected allergy or reaction to any component of the IMP formulation.
15. History of any active skin infection within 1 week prior to randomisation.

16. History of a clinically significant infection within 4 weeks prior to randomisation which, in the opinion of the investigator or sponsor's medical expert, may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. Clinically significant infections are defined as:

    • a systemic infection.
    • a serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.
17. A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
18. History of anaphylaxis following any biologic therapy.
19. History of immune complex disease.

20. History of cancer:

    • Subjects who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
    • Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
21. Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care.
22. History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications as determined by medical history and/or subject's verbal report.
23. History of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator.
24. History of attempted suicide or is at significant risk of suicide (either in the opinion of the investigator or defined as a "yes" to suicidal ideation questions no. 4 or 5 or answering "yes" to suicidal behaviour on the Columbia-Suicide Severity Rating Scale [C-SSRS] Screening version).

25. Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could:

    • Affect the safety of the subject throughout the trial.
    • Influence the findings of the trial or their interpretations.
    • Impede the subject's ability to complete the entire duration of trial.
26. Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during the screening period, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the trial, or may influence the results of the trial, or the subject's ability to complete entire duration of the trial.
27. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the ULN (upper limit of normal) at screening.
28. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.
29. Subjects who are not willing to abstain from donating blood and/or plasma from the time of informed consent and for 16 weeks (5 half-lives) after last dose of IMP.
30. Subjects who are legally institutionalised.
31. Pregnant, breastfeeding, or lactating women.
32. Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Initial treatment period - Tralokinumab Q2W; Week 0 to Week 16 Two subcutaneous (SC) injections of tralokinumab as a loading dose on Day 0, followed by a SC injection of tralokinumab Q2W regimen for 16 weeks	Drug: Tralokinumab; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration
Placebo Comparator: Initial treatment period - Placebo; Week 0 to Week 16 (Initial treatment period): Two subcutaneous (SC) injections of placebo as a loading dose on Day 0 followed by a SC injection of placebo Q2W regimen for 16 weeks	Drug: Placebo; Placebo contains the same excipients, in the same concentration only lacking tralokinumab
Experimental: Maintenance treatment period - Tralokinumab Q2W; Week 16 to Week 52 Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q2W for 36 weeks	Drug: Tralokinumab; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration
Experimental: Maintenance treatment period - Tralokinumab Q4W; Week 16 to Week 52 Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q4W for 36 weeks. Participants in this group receive alternating doses of tralokinumab SC injection and placebo SC injection every 2 weeks	Drug: Tralokinumab; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration; Drug: Placebo; Placebo contains the same excipients, in the same concentration only lacking tralokinumab
Placebo Comparator: Maintenance treatment period - Placebo; Week 16 to Week 52 Tralokinumab responders from initial treatment period randomised at Week 16 and administered placebo subcutaneous maintenance injection for 36 weeks	Drug: Placebo; Placebo contains the same excipients, in the same concentration only lacking tralokinumab
Placebo Comparator: Maintenance treatment period - Placebo (tralokinumab naive); Week 16 to Week 52 Placebo responders from the initial treatment period re-assigned at Week 16 and administered placebo maintenance subcutaneous injection regimen Q2W for 36 weeks	Drug: Placebo; Placebo contains the same excipients, in the same concentration only lacking tralokinumab
Experimental: Open-label treatment - Tralokinumab 300 mg Q2W + optional TCS; Week 16 to Week 52 Subjects receiving initial treatment with tralokinumab Q2W or placebo Q2W assigned to open-label treatment at Week 16 and administered tralokinumab subcutaneous (SC) injection + optional TCS* regimen Q2W OR Subjects receiving maintenance treatment with tralokinumab Q2W/Q4W or placebo assigned to open-label treatment after Week 16 and administered tralokinumab SC injection + optional TCS regimen Q2W • TCS = topical corticosteroids	Drug: Tralokinumab; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) 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).	At Week 16
Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI].	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.	At Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.	Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.	Week 0 to Week 16
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16	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).	At Week 52
Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 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.	At Week 52
Safety and Tolerability: Adverse Event (AE) /Serious Adverse Event (SAE) Frequency	Overall summary of AEs and SAEs during the Initial treatment period is presented. For list of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.	Week 0 to Week 16
Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] 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.	At Week 16
Change in Scoring Atopic Dermatitis (SCORAD) From Baseline 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.	Week 0 to Week 16
Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16.	The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their quality of life (QoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.	Week 0 to Week 16
Frequency of Anti-drug Antibodies	Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method	Week 0 to Week 16
Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] 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.	At Week 16
Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score	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.	At Week 16
Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at 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.	At Week 16
Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at 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.	At Week 16
Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average).	Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'	Baseline to Week 16
Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16.	Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.	Baseline to Week 16
Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4.	The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.	Baseline to Week 16

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Eric Simpson, MD, MCR, Department of Dermatology, Oregon Health and Science University

Publications and helpful links

General Publications

• Simpson EL, Merola JF, Silverberg JI, Reich K, Warren RB, Staumont-Salle D, Girolomoni G, Papp K, de Bruin-Weller M, Thyssen JP, Zachariae R, Olsen CK, Wollenberg A. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br J Dermatol. 2022 Dec;187(6):888-899. doi: 10.1111/bjd.21867. Epub 2022 Oct 26.
• Blauvelt A, Gooderham M, Bhatia N, Langley RG, Schneider S, Zoidis J, Kurbasic A, Armstrong A, Silverberg JI. Tralokinumab Efficacy and Safety, with or without Topical Corticosteroids, in North American Adults with Moderate-to-Severe Atopic Dermatitis: A Subanalysis of Phase 3 Trials ECZTRA 1, 2, and 3. Dermatol Ther (Heidelb). 2022 Nov;12(11):2499-2516. doi: 10.1007/s13555-022-00805-y. Epub 2022 Sep 24.
• Wollenberg A, Blauvelt A, Guttman-Yassky E, Worm M, Lynde C, Lacour JP, Spelman L, Katoh N, Saeki H, Poulin Y, Lesiak A, Kircik L, Cho SH, Herranz P, Cork MJ, Peris K, Steffensen LA, Bang B, Kuznetsova A, Jensen TN, Osterdal ML, Simpson EL; ECZTRA 1 and ECZTRA 2 study investigators. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021 Mar;184(3):437-449. doi: 10.1111/bjd.19574. Epub 2020 Dec 30.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Actual): September 4, 2018
• Study Completion (Actual): August 14, 2019

Study Registration Dates

• First Submitted: May 18, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: LP0162-1326; 2016-004201-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified Individual Participant Data can be made available to researchers in a closed environment for a specified period of time.
• IPD Sharing Time Frame: Data are available to request after results of the trial are available on leopharmatrials.com
• IPD Sharing Access Criteria: Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No