Tralokinumab in Combination With Topical Corticosteroids for Moderate to Severe Atopic Dermatitis - ECZTRA 3

A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Tralokinumab in Combination With Topical Corticosteroids in Subjects With Moderate to Severe Atopic Dermatitis

Primary objective:

To demonstrate that tralokinumab in combination with topical corticosteroids (TCS) is superior to placebo in combination with TCS in treating moderate-to-severe atopic dermatitis (AD).

Secondary objectives:

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

To assess the safety of tralokinumab in combination with TCS when used to treat moderate-to-severe AD for 32 weeks.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2650
    • University Hospital Antwerp
  • Brussels, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Loverval, Belgium, 6280
    • LEO Pharma Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • Institute For Skin Advancement
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • Skin Care Centre
  • New Brunswick
    • Bathurst, New Brunswick, Canada, E2A 4Z9
      • Maritime Medical Research Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1Z4
      • Eastern Canada Cutaneous Research
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • CCA Medical Research
    • Barrie, Ontario, Canada, L4M 6L2
      • SimcoDerm Medical and Surgical Dermatology Centre
    • Mississauga, Ontario, Canada, L5H 1G9
      • DermEdge Research
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • York Dermatology Center
    • Toronto, Ontario, Canada, M4W 2N2
      • Research Toronto
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research
• Germany
  • Berlin, Germany, 10780
    • Interdisciplinary Study Association GmbH
  • Bochum, Germany, 44791
    • St. Josef-Hospital, Ruhr-Universitet
  • Bonn, Germany, 53105
    • Klinik und Poliklinik fur Dermatologie und Allergologie
  • Frankfurt am Main, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universität Klinik
  • Hamburg, Germany, 22391
    • MensingDerma research GmbH
  • Jena, Germany, 07743
    • Universitatsklinikum Jena
  • Kiel, Germany, 24105
    • Universitätshautklinik Kiel
  • Tuebingen, Germany, 72076
    • Universitätsklinikum Tübingen
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amcademic Medical Center
  • Bergen Op Zoom, Netherlands, 4614 VT
    • LEO Pharma Investigational Site
  • Groningen, Netherlands, 9713 GZ
    • LEO Pharma Investigational Site
  • Nijmegen, Netherlands, 6525
    • Radboud MC
  • Rotterdam, Netherlands, 3015 CA
    • Erasmus MC, Rotterdam
  • Utrecht, Netherlands, 3584 CX
    • University Medical Centre Utrecht
• Poland
  • Lublin, Poland, 20-146
    • Nzoz Med-Laser
  • Rzeszów, Poland, 35-055
    • LEO Pharma Investigational Site
  • Warszawa, Poland, 01-0141
    • Wojskowy Instytut Medyczny
  • Wroclaw, Poland, 50-001
    • Wromedica s.c.
  • Wrocław, Poland, 51-318
    • Derm Medica Sp.zo.o.
• Spain
  • Alicante, Spain, 03010
    • Hospital General de Alicante
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Madrid, Spain, 28922
    • Fundacion Hospital Alcorcon
  • Pontevedra, Spain, 36003
    • Hospital de Pontevedra
  • Valencia, Spain, 46014
    • Hospital General de Valencia
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • The Royal Free Hospital
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbooke's Hospital
  • Essex
    • Harlow, Essex, United Kingdom, CM20 1QX
      • The Princess Alexandra Hospital
  • Surrey
    • Redhill, Surrey, United Kingdom, RH1 5RH
      • East Surrey Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital Birmingham
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Russells Hall Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama-Birmingham
  • California
    • Encinitas, California, United States, 92024
      • California Dermatology & Clinical Research Institute
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
    • Fremont, California, United States, 94538
      • Center for Dermatology Clinical Research
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Clinical Research
  • Florida
    • Miami, Florida, United States, 33144
      • International Dermatology Research
    • Miami, Florida, United States, 33144
      • L & C Professional Medical Research
    • Sweetwater, Florida, United States, 33172
      • Lenus Research & Medical Group
    • Tampa, Florida, United States, 33614
      • Olympian Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Medical Dermatology Specialists
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • Indiana Clinical Trials Center
  • Maine
    • Bangor, Maine, United States, 04401
      • Study Center
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
      • Respiratory Medicine Research
  • New York
    • New York, New York, United States, 10023
      • Mount Sinai West Dermatoogy
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research
  • Ohio
    • Bexley, Ohio, United States, 43209
      • Dermatologists of Greater Columbus
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology & Research
  • South Carolina
    • North Charleston, South Carolina, United States, 29420
      • National Allergy and Asthma Research, LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18 and above.
• Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD.
• History of AD for ≥1 year.
• Subjects who have a recent history of inadequate response to treatment with topical medications.
• 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:

• Subjects for whom TCS are medically inadvisable e.g., due to important side effects or safety risks in the opinion of the investigator.
• 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, topical calcineurin inhibitors (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 E) including dupilumab or investigational biologic agents within 3 months or 5 half-lives, whichever is longer prior to randomisation.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tralokinumab(initial)responders-> Tralokinumab(continuation A); Week 0 to 16 (initial period): Tralokinumab loading SC injection on Day 0 followed by tralokinumab injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen A.	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: Tralokinumab(initial)responders-> Tralokinumab(continuation B); Week 0 to 16 (initial period): Tralokinumab loading SC injection on Day 0 followed by tralokinumab injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen B.	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: Tralokinumab(initial)non-respon-> Tralokinumab(continuation A); Week 0 to 16 (initial period): Tralokinumab loading SC injection on Day 0 followed by tralokinumab injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen A.	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: Placebo (initial)non-respon-> Tralokinumab(continuation A); Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen A.	Drug: Placebo; Placebo contains the same excipients in the same concentration only lacking tralokinumab.; Drug: Tralokinumab; Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration.
Placebo Comparator: Placebo(initial)responders-> Placebo(continuation A); Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 32 (continuation period): Placebo continuation SC injection regimen A.	Drug: Placebo; Placebo contains the same excipients in the same concentration only lacking tralokinumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16	IGA is used to evaluate the severity of atopic dermatitis. It is a 5-point score ranging from 0 (clear) to 4 (severe).	Week 16
Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16	EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition.	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16	Worst Daily Pruritus NRS is used by the participant to evaluate their worst itch severity over the past 24 hours. The score ranges from 0 ('no itch') to 10 ('worst itch imaginable') on an 11-point scale.	Week 0 to Week 16
Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16	SCORAD is used to evaluate the extent and severity of atopic dermatitis as well as subjective symptoms. The score ranges from 0 to 103 with a higher score indicating a more extensive and/or severe condition.	Week 0 to Week 16
Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16	DLQI is used by the participant to evaluate the impact of their condition on 10 different aspects of health-related quality of life (HRQoL) over the last week. Each item is scored on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much). The total score which is the sum of the 10 items ranges from 0 to 30, with a higher score indicating a poorer HRQoL.	Week 0 to Week 16
Frequency of Anti-drug Antibodies (ADA)	Presence of ADA from Week 0 to Week 32 was measured. Data were reported in the following categories: positive (presence of ADA at baseline and/or presence of ADA at at least 1 post-baseline assessment), perishing (presence of ADA at baseline and absence of ADA at all post-baseline assessments), negative (absence of ADA at all assessments), no post-baseline ADA assessment. Perishing ADAs were not assessed in the continuation treatment period.	Week 0 to Week 16, Week 16 to Week 32
Amount of Topical Corticosteroid (TCS) Used Through Week 16 Assuming no TCS Used From the Non-returned Tubes	Assessed as the amount of TCS weighed from previous visits, assuming no TCS was used from the non-returned tubes. Measurements were collected as TCS weight (g) between the visits.	Week 1-2 to Week 15-16
Amount of Topical Corticosteroid (TCS) Used Through Week 16 Assuming All TCS Used From the Non-returned Tubes	Assessed as the amount of TCS weighed from previous visits, assuming all TCS was used from the non-returned tubes. Measurements were collected as TCS weight (g) between the visits.	Week 1-2 to Week 15-16
Number of Atopic Dermatitis Flares Through Week 16	Assessed as appearance of new flares since previous visit.	Week 0 to Week 16
Number of Days Without Topical Treatment Use From Baseline to Week 16	Participants assessed their use of topical treatment over the past 24 hours using a response scale ('yes', 'no'). Measurements of number of days per week were used in the analysis.	Week 1 to Week 16
Participants Achieving at Least 50% Reduction in Eczema Area and Severity Index (EASI) at Week 16	EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition.	Week 16
Participants Achieving at Least 90% Reduction in Eczema Area and Severity Index (EASI) at Week 16	EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition.	Week 16
Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score	EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition.	Week 0 to Week 16
Participants Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16	SCORAD is used to evaluate the extent and severity of atopic dermatitis as well as subjective symptoms. The score ranges from 0 to 103 with a higher score indicating a more extensive and/or severe condition.	Week 16
Participants Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16	SCORAD is used to evaluate the extent and severity of atopic dermatitis as well as subjective symptoms. The score ranges from 0 to 103 with a higher score indicating a more extensive and/or severe condition.	Week 16
Change From Baseline to Week 16 in Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average)	Worst Daily Pruritus NRS is used by the participant to evaluate their worst itch severity over the past 24 hours. The score ranges from 0 ('no itch') to 10 ('worst itch imaginable') on an 11-point scale.	Week 0 to Week 16
Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of at Least 4 Points Among Participants With Baseline DLQI ≥4	DLQI is used by the participant to evaluate the impact of their condition on 10 different aspects of health-related quality of life (HRQoL) over the last week. Each item is scored on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much). The total score which is the sum of the 10 items ranges from 0 to 30, with a higher score indicating a poorer HRQoL.	Week 0 to Week 16
Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 32 Among Participants With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab	IGA is used to evaluate the severity of atopic dermatitis. It is a 5-point score ranging from 0 (clear) to 4 (severe).	Week 32
Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 32 Among Participants Who Had Achieved at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab	EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition.	Week 32

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Study Director: Medical Expert, LEO Pharma

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.
• Silverberg JI, Adam DN, Zirwas M, Kalia S, Gutermuth J, Pinter A, Pink AE, Chiricozzi A, Barbarot S, Mark T, Tindberg AM, Weidinger S. Tralokinumab Plus Topical Corticosteroids as Needed Provides Progressive and Sustained Efficacy in Adults with Moderate-to-Severe Atopic Dermatitis Over a 32-Week Period: An ECZTRA 3 Post Hoc Analysis. Am J Clin Dermatol. 2022 Jul;23(4):547-559. doi: 10.1007/s40257-022-00702-2. Epub 2022 Jul 20.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2018
• Primary Completion (Actual): March 8, 2019
• Study Completion (Actual): September 26, 2019

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis, Atopic; Dermatitis; Eczema
• Other Study ID Numbers: LP0162-1339; 2017-002065-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified IPD 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: De-identified Individual Participant Data can be made available to researchers and is subject to approved scientifically sound research proposal and signed data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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