Clinical trial NCT03363854: Tralokinumab in Combination With Topical Corticosteroids for Moderate to Severe Atopic Dermatitis - ECZTRA 3
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2017-12-06
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
timeFrame: Week 16
measure: Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16
timeFrame: Week 0 to Week 16
measure: Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16
timeFrame: Week 0 to Week 16
measure: Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16
timeFrame: Week 0 to Week 16
measure: Frequency of Anti-drug Antibodies (ADA)
timeFrame: Week 0 to Week 16, Week 16 to Week 32
measure: Amount of Topical Corticosteroid (TCS) Used Through Week 16 Assuming no TCS Used From the Non-returned Tubes
timeFrame: Week 1-2 to Week 15-16
measure: Amount of Topical Corticosteroid (TCS) Used Through Week 16 Assuming All TCS Used From the Non-returned Tubes
timeFrame: Week 1-2 to Week 15-16
measure: Number of Atopic Dermatitis Flares Through Week 16
timeFrame: Week 0 to Week 16
measure: Number of Days Without Topical Treatment Use From Baseline to Week 16
timeFrame: Week 1 to Week 16
measure: Participants Achieving at Least 50% Reduction in Eczema Area and Severity Index (EASI) at Week 16
timeFrame: Week 16
measure: Participants Achieving at Least 90% Reduction in Eczema Area and Severity Index (EASI) at Week 16
timeFrame: Week 16
measure: Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
timeFrame: Week 0 to Week 16
measure: Participants Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16
timeFrame: Week 16
measure: Participants Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16
timeFrame: Week 16
measure: Change From Baseline to Week 16 in Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average)
timeFrame: Week 0 to Week 16
measure: Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of at Least 4 Points Among Participants With Baseline DLQI ≥4
timeFrame: Week 0 to Week 16
measure: 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
timeFrame: Week 32
measure: 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
timeFrame: Week 32
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama-Birmingham
state: Alabama
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Fremont
country: United States
facility: Center for Dermatology Clinical Research
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute
state: California
city: Danbury
country: United States
facility: Danbury Clinical Research
state: Connecticut
city: Miami
country: United States
facility: International Dermatology Research
state: Florida
city: Miami
country: United States
facility: L & C Professional Medical Research
state: Florida
city: Sweetwater
country: United States
facility: Lenus Research & Medical Group
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Medical Dermatology Specialists
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Plainfield
country: United States
facility: Indiana Clinical Trials Center
state: Indiana
city: Bangor
country: United States
facility: Study Center
state: Maine
city: Ypsilanti
country: United States
facility: Respiratory Medicine Research
state: Michigan
city: New York
country: United States
facility: Mount Sinai West Dermatoogy
state: New York
city: Raleigh
country: United States
facility: Wake Research
state: North Carolina
city: Bexley
country: United States
facility: Dermatologists of Greater Columbus
state: Ohio
city: Portland
country: United States
facility: Oregon Dermatology & Research
state: Oregon
city: North Charleston
country: United States
facility: National Allergy and Asthma Research, LLC
state: South Carolina
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Brussels
country: Belgium
facility: Universitair ziekenhuis Brussel
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Loverval
country: Belgium
facility: LEO Pharma Investigational Site
city: Calgary
country: Canada
facility: Institute for Skin Advancement
state: Alberta
city: Vancouver
country: Canada
facility: Skin Care Centre
state: British Columbia
city: Bathurst
country: Canada
facility: Maritime Medical Research Centre
state: New Brunswick
city: Halifax
country: Canada
facility: Eastern Canada Cutaneous Research
state: Nova Scotia
city: Ajax
country: Canada
facility: CCA Medical Research
state: Ontario
city: Barrie
country: Canada
facility: Simcoderm Medical and Surgical Dermatology Centre
state: Ontario
city: Mississauga
country: Canada
facility: DermEdge Research
state: Ontario
city: Richmond Hill
country: Canada
facility: York Dermatology Center
state: Ontario
city: Toronto
country: Canada
facility: Research Toronto
state: Ontario
city: Windsor
country: Canada
facility: XLR8 Medical Research
state: Ontario
city: Berlin
country: Germany
facility: Interdisciplinary Study Association GmbH
city: Bochum
country: Germany
facility: St. Josef-Hospital, Ruhr-Universitet
city: Bonn
country: Germany
facility: Klinik und Poliklinik für Dermatologie und Allergologie
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universität Klinik
city: Hamburg
country: Germany
facility: MensingDerma Research GmbH
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kiel
country: Germany
facility: Universitätshautklinik Kiel
city: Tuebingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Amsterdam
country: Netherlands
facility: Amcademic Medical Center
city: Bergen Op Zoom
country: Netherlands
facility: LEO Pharma Investigational Site
city: Groningen
country: Netherlands
facility: LEO Pharma Investigational Site
city: Nijmegen
country: Netherlands
facility: Radboud MC
city: Rotterdam
country: Netherlands
facility: Erasmus MC, Rotterdam
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Lublin
country: Poland
facility: Nzoz Med-Laser
city: Rzeszów
country: Poland
facility: LEO Pharma Investigational Site
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny
city: Wroclaw
country: Poland
facility: Wromedica s.c.
city: Wrocław
country: Poland
facility: Derm Medica Sp.zo.o.
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Fundación Hospital Alcorcón
city: Pontevedra
country: Spain
facility: Hospital de Pontevedra
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Cambridge
country: United Kingdom
facility: Addenbooke's Hospital
state: Cambridgeshire
city: Harlow
country: United Kingdom
facility: The Princess Alexandra Hospital
state: Essex
city: Redhill
country: United Kingdom
facility: East Surrey Hospital
state: Surrey
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
state: West Midlands
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: West Midlands
city: London
country: United Kingdom
facility: The Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
Study officials:
affiliation: LEO Pharma
name: Medical expert
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.