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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03526861
• Other study ID #: LP0162-1334
• Secondary ID: 2017-005143-33
• Status: Completed
• Phase: Phase 3
• Start date: June 19, 2018
• Est. completion date: March 16, 2021

Study information

• Verified date: May 2023
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 301
• Est. completion date: March 16, 2021
• Est. primary completion date: April 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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 E) 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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

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

Locations

Country	Name	City	State
Australia	Leo Pharma Investigationel Site	Darlinghurst
Australia	Leo Pharma Investigationel Site	Kogarah
Australia	Leo Pharma Investigationel Site	Melbourne
Australia	Leo Pharma Investigationel Site	Woolloongabba
Belgium	Leo Pharma Investigationel Site	Brussels
Belgium	Leo Pharma Investigationel Site	Gent
Belgium	Leo Pharma Investigationel Site	Liège
Belgium	Leo Pharma Investigational Site	Maldegem
Canada	LEO Pharma Investigational Site	Calgary	Alberta
Canada	LEO Pharma Investigational Site	Edmonton	Alberta
Canada	LEO Pharma Investigational Site	Markham	Ontario
Canada	LEO Pharma Investigational Site	Montreal	Quebec
Canada	LEO Pharma Investigational Site	Oakville	Ontario
Canada	LEO Pharma Investigational Site	Saskatoon	Saskatchewan
Canada	LEO Pharma Investigational Site	Surrey	British Columbia
Canada	LEO Pharma Investigational Site	Toronto	Ontario
Canada	LEO Pharma Investigational Site	Windsor	Ontario
Canada	LEO Pharma Investigational Site	Winnipeg	Manitoba
Canada	LEO Pharma Investigational Site	Winnipeg	Manitoba
France	Leo Pharma Investigationel Site	Marseille
France	Leo Pharma Investigationel Site	Nice
France	Leo Pharma Investigationel Site	Paris
France	Leo Pharma Investigationel Site	Paris
France	Leo Pharma Investigationel Site	Valence
Germany	Leo Pharma Investigationel Site	Berlin
Germany	Leo Pharma Investigationel Site	Dresden
Germany	Leo Pharma Investigationel Site	Jena
Germany	Leo Pharma Investigationel Site	Osnabrück
Japan	Leo Pharma Investigationel Site	Fukuoka
Japan	Leo Pharma Investigationel Site	Kagoshima city
Japan	Leo Pharma Investigationel Site	Kyoto
Japan	Leo Pharma Investigationel Site	Nagoya-shi
Japan	Leo Pharma Investigationel Site	Obihiro
Japan	Leo Pharma Investigationel Site	Osaka
Japan	Leo Pharma Investigationel Site	Osaka-fu
Japan	Leo Pharma Investigationel Site	Shimotsuke
Japan	Leo Pharma Investigationel Site	Tokyo
Japan	Leo Pharma Investigationel Site	Tokyo
Japan	Leo Pharma Investigationel Site	Tokyo
Japan	Leo Pharma Investigationel Site	Tokyo
Japan	Leo Pharma Investigationel Site	Tsu
Japan	Leo Pharma Investigationel Site	Yamanashi
Netherlands	Leo Pharma Investigationel Site	Bergen Op Zoom
Netherlands	Leo Pharma Investigationel Site	Breda
Netherlands	Leo Pharma Investigationel Site	Groningen
Netherlands	Leo Pharma Investigationel Site	Rotterdam
Poland	Leo Pharma Investigationel Site	Kraków
Poland	Leo Pharma Investigationel Site	Kraków
Poland	Leo Pharma Investigationel Site	Kraków
Poland	Leo Pharma Investigationel Site	Lódz
Poland	Leo Pharma Investigationel Site	Lódz
Poland	Leo Pharma Investigationel Site	Rzeszów
Poland	Leo Pharma Investigationel Site	Swidnik
Poland	Leo Pharma Investigationel Site	Wroclaw
Poland	Leo Pharma Investigationel Site	Wroclaw
Poland	Leo Pharma Investigationel Site	Wroclaw
United Kingdom	Leo Pharma Investigationel Site	Glasgow
United Kingdom	Leo Pharma Investigationel Site	London
United States	Leo Pharma Investigational Site	Albany	Georgia
United States	LEO Pharma Investigational Site	Ann Arbor	Michigan
United States	LEO Pharma Investigational Site	Austin	Texas
United States	LEO Pharma Investigational Site	Baton Rouge	Louisiana
United States	LEO Pharma Investigational Site	Bexley	Ohio
United States	LEO Pharma Investigational Site	Birmingham	Alabama
United States	LEO Pharma Investigational Site	Chicago	Illinois
United States	LEO Pharma Investigational Site	Corning	New York
United States	LEO Pharma Investigational Site	East Windsor	New Jersey
United States	LEO Pharma Investigational Site	Fort Smith	Arkansas
United States	Leo Pharma Investigational Site	Fountain Valley	California
United States	LEO Pharma Investigational Site	High Point	North Carolina
United States	LEO Pharma Investigational Site	Houston	Texas
United States	LEO Pharma Investigational Site	Los Angeles	California
United States	LEO Pharma Investigational Site	Louisville	Kentucky
United States	LEO Pharma Investigational Site	Miami	Florida
United States	LEO Pharma Investigational Site	Minneapolis	Minnesota
United States	Leo Pharma Investigational Site	Murfreesboro	Tennessee
United States	LEO Pharma Investigational Site	New Haven	Connecticut
United States	Leo Pharma Investigational Site	New York	New York
United States	Leo Pharma Investigational Site	North Charleston	South Carolina
United States	LEO Pharma Investigational Site	Philadelphia	Pennsylvania
United States	LEO Pharma Investigational Site	Portland	Oregon
United States	LEO Pharma Investigational Site	Portland	Oregon
United States	Leo Pharma Investigational Site	San Antonio	Texas
United States	LEO Pharma Investigational Site	San Francisco	California
United States	LEO Pharma Investigational Site	Stanford	California
United States	Leo Pharma Investigational Site	Tulsa	Oklahoma
United States	LEO Pharma Investigational Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Japan,  Netherlands,  Poland,  United Kingdom, 

References & Publications (1)

Paller AS, Flohr C, Cork M, Bewley A, Blauvelt A, Hong HC, Imafuku S, Schuttelaar MLA, Simpson EL, Soong W, Arlert P, Lophaven KW, Kurbasic A, Soldbro L, Vest NS, Wollenberg A. Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Ato — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Subjects With at Least 75% Reduction in Eczema Area and Severity Index (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 16
Secondary	Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline 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'.	At Week 16
Secondary	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.	From Week 0 to Week 16
Secondary	Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline 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.	From Week 0 to Week 16
Secondary	Number of Adverse Events	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.	From Week 0 to Week 16
Secondary	Presence of Anti-drug Antibodies	Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method.	From Week 0 to Week 16
Secondary	Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) 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
Secondary	Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) 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
Secondary	Change in Eczema Area and Severity Index (EASI) Score From Baseline 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.	From Week 0 to Week 16
Secondary	Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) 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.	At Week 16
Secondary	Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) 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.	At Week 16
Secondary	Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline 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'.	From Week 0 to Week 16
Secondary	Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline 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'.	At Week 16
Secondary	Change in Patient Oriented Eczema Measure (POEM) From Baseline 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.	From Week 0 to Week 16
Secondary	Tralokinumab Serum Trough Concentration at Week 16	Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.	At Week 16
Secondary	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	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
Secondary	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	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
Secondary	Tralokinumab Serum Trough Concentration at Week 66	Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.	At Week 66