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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03363854
• Other study ID #: LP0162-1339
• Secondary ID: 2017-002065-21
• Status: Completed
• Phase: Phase 3
• Start date: February 22, 2018
• Est. completion date: September 26, 2019

Study information

• Verified date: February 2021
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: September 26, 2019
• Est. primary completion date: March 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

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
Placebo contains the same excipients in the same concentration only lacking tralokinumab.

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Belgium	Cliniques Universitaires St-Luc	Brussels
Belgium	Universitair ziekenhuis Brussel	Brussels
Belgium	LEO Pharma Investigational Site	Loverval
Canada	CCA Medical Research	Ajax	Ontario
Canada	Simcoderm Medical and Surgical Dermatology Centre	Barrie	Ontario
Canada	Maritime Medical Research Centre	Bathurst	New Brunswick
Canada	Institute for Skin Advancement	Calgary	Alberta
Canada	Eastern Canada Cutaneous Research	Halifax	Nova Scotia
Canada	DermEdge Research	Mississauga	Ontario
Canada	York Dermatology Center	Richmond Hill	Ontario
Canada	Research Toronto	Toronto	Ontario
Canada	Skin Care Centre	Vancouver	British Columbia
Canada	XLR8 Medical Research	Windsor	Ontario
Germany	Interdisciplinary Study Association GmbH	Berlin
Germany	St. Josef-Hospital, Ruhr-Universitet	Bochum
Germany	Klinik und Poliklinik für Dermatologie und Allergologie	Bonn
Germany	Klinikum der Johann Wolfgang Goethe-Universität Klinik	Frankfurt am Main
Germany	MensingDerma Research GmbH	Hamburg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätshautklinik Kiel	Kiel
Germany	Universitätsklinikum Tübingen	Tuebingen
Netherlands	Amcademic Medical Center	Amsterdam
Netherlands	LEO Pharma Investigational Site	Bergen Op Zoom
Netherlands	LEO Pharma Investigational Site	Groningen
Netherlands	Radboud MC	Nijmegen
Netherlands	Erasmus MC, Rotterdam	Rotterdam
Netherlands	University Medical Centre Utrecht	Utrecht
Poland	Nzoz Med-Laser	Lublin
Poland	LEO Pharma Investigational Site	Rzeszów
Poland	Wojskowy Instytut Medyczny	Warszawa
Poland	Derm Medica Sp.zo.o.	Wroclaw
Poland	Wromedica s.c.	Wroclaw
Spain	Hospital General de Alicante	Alicante
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Fundación Hospital Alcorcón	Madrid
Spain	Hospital de Pontevedra	Pontevedra
Spain	Hospital General de Valencia	Valencia
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham	West Midlands
United Kingdom	Addenbooke's Hospital	Cambridge	Cambridgeshire
United Kingdom	Russells Hall Hospital	Dudley	West Midlands
United Kingdom	The Princess Alexandra Hospital	Harlow	Essex
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	The Royal Free Hospital	London
United Kingdom	East Surrey Hospital	Redhill	Surrey
United States	Medical Dermatology Specialists	Atlanta	Georgia
United States	Study Center	Bangor	Maine
United States	Dermatologists of Greater Columbus	Bexley	Ohio
United States	University of Alabama-Birmingham	Birmingham	Alabama
United States	Northwestern University	Chicago	Illinois
United States	Danbury Clinical Research	Danbury	Connecticut
United States	California Dermatology & Clinical Research Institute	Encinitas	California
United States	First OC Dermatology	Fountain Valley	California
United States	Center for Dermatology Clinical Research	Fremont	California
United States	Dermatology Research Associates	Los Angeles	California
United States	International Dermatology Research	Miami	Florida
United States	L & C Professional Medical Research	Miami	Florida
United States	Mount Sinai West Dermatoogy	New York	New York
United States	National Allergy and Asthma Research, LLC	North Charleston	South Carolina
United States	Indiana Clinical Trials Center	Plainfield	Indiana
United States	Oregon Dermatology & Research	Portland	Oregon
United States	Wake Research	Raleigh	North Carolina
United States	Clinical Science Institute	Santa Monica	California
United States	Lenus Research & Medical Group	Sweetwater	Florida
United States	Olympian Clinical Research	Tampa	Florida
United States	Respiratory Medicine Research	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Atopic Dermatitis Flares Through Week 16	Assessed as appearance of new flares since previous visit.	Week 0 to Week 16
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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