Clinical trial NCT03526861: Tralokinumab Monotherapy for Adolescent Subjects With Moderate to Severe Atopic Dermatitis - ECZTRA 6 (ECZema TRAlokinumab Trial no. 6).
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2018-05-16
Enrollment: 301
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
timeFrame: At Week 16
measure: Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16
timeFrame: At Week 16
Secondary outcomes:
measure: Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16
timeFrame: At Week 16
measure: Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16
timeFrame: From Week 0 to Week 16
measure: Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16
timeFrame: From Week 0 to Week 16
measure: Number of Adverse Events
timeFrame: From Week 0 to Week 16
measure: Presence of Anti-drug Antibodies
timeFrame: From Week 0 to Week 16
measure: Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16.
timeFrame: At Week 16
measure: Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16.
timeFrame: At Week 16
measure: Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16
timeFrame: From Week 0 to Week 16
measure: Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16
timeFrame: At Week 16
measure: Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16
timeFrame: At Week 16
measure: Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16
timeFrame: From Week 0 to Week 16
measure: Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16
timeFrame: At Week 16
measure: Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16
timeFrame: From Week 0 to Week 16
measure: Tralokinumab Serum Trough Concentration at Week 16
timeFrame: At Week 16
measure: 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
timeFrame: At Week 52
measure: 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
timeFrame: At Week 52
measure: Tralokinumab Serum Trough Concentration at Week 66
timeFrame: At Week 66
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: LEO Pharma Investigational Site
state: Alabama
city: Fort Smith
country: United States
facility: LEO Pharma Investigational Site
state: Arkansas
city: Fountain Valley
country: United States
facility: Leo Pharma Investigational Site
state: California
city: Los Angeles
country: United States
facility: LEO Pharma Investigational Site
state: California
city: San Francisco
country: United States
facility: LEO Pharma Investigational Site
state: California
city: Stanford
country: United States
facility: LEO Pharma Investigational Site
state: California
city: New Haven
country: United States
facility: LEO Pharma Investigational Site
state: Connecticut
city: Miami
country: United States
facility: LEO Pharma Investigational Site
state: Florida
city: Albany
country: United States
facility: Leo Pharma Investigational Site
state: Georgia
city: Chicago
country: United States
facility: LEO Pharma Investigational Site
state: Illinois
city: Louisville
country: United States
facility: LEO Pharma Investigational Site
state: Kentucky
city: Baton Rouge
country: United States
facility: LEO Pharma Investigational Site
state: Louisiana
city: Ann Arbor
country: United States
facility: LEO Pharma Investigational Site
state: Michigan
city: Ypsilanti
country: United States
facility: LEO Pharma Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: LEO Pharma Investigational Site
state: Minnesota
city: East Windsor
country: United States
facility: LEO Pharma Investigational Site
state: New Jersey
city: Corning
country: United States
facility: LEO Pharma Investigational Site
state: New York
city: New York
country: United States
facility: Leo Pharma Investigational Site
state: New York
city: High Point
country: United States
facility: LEO Pharma Investigational Site
state: North Carolina
city: Bexley
country: United States
facility: LEO Pharma Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: Leo Pharma Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: LEO Pharma Investigational Site
state: Oregon
city: Portland
country: United States
facility: LEO Pharma Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: LEO Pharma Investigational Site
state: Pennsylvania
city: North Charleston
country: United States
facility: Leo Pharma Investigational Site
state: South Carolina
city: Murfreesboro
country: United States
facility: Leo Pharma Investigational Site
state: Tennessee
city: Austin
country: United States
facility: LEO Pharma Investigational Site
state: Texas
city: Houston
country: United States
facility: LEO Pharma Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Leo Pharma Investigational Site
state: Texas
city: Darlinghurst
country: Australia
facility: Leo Pharma Investigationel Site
city: Kogarah
country: Australia
facility: Leo Pharma Investigationel Site
city: Melbourne
country: Australia
facility: Leo Pharma Investigationel Site
city: Woolloongabba
country: Australia
facility: Leo Pharma Investigationel Site
city: Brussels
country: Belgium
facility: Leo Pharma Investigationel Site
city: Gent
country: Belgium
facility: Leo Pharma Investigationel Site
city: Liège
country: Belgium
facility: Leo Pharma Investigationel Site
city: Maldegem
country: Belgium
facility: Leo Pharma Investigational Site
city: Calgary
country: Canada
facility: LEO Pharma Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: LEO Pharma Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: LEO Pharma Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: LEO Pharma Investigational Site
state: Manitoba
city: Winnipeg
country: Canada
facility: LEO Pharma Investigational Site
state: Manitoba
city: Markham
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: LEO Pharma Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: LEO Pharma Investigational Site
state: Saskatchewan
city: Marseille
country: France
facility: Leo Pharma Investigationel Site
city: Nice
country: France
facility: Leo Pharma Investigationel Site
city: Paris
country: France
facility: Leo Pharma Investigationel Site
city: Paris
country: France
facility: Leo Pharma Investigationel Site
city: Valence
country: France
facility: Leo Pharma Investigationel Site
city: Berlin
country: Germany
facility: Leo Pharma Investigationel Site
city: Dresden
country: Germany
facility: Leo Pharma Investigationel Site
city: Jena
country: Germany
facility: Leo Pharma Investigationel Site
city: Osnabrück
country: Germany
facility: Leo Pharma Investigationel Site
city: Fukuoka
country: Japan
facility: Leo Pharma Investigationel Site
city: Kagoshima city
country: Japan
facility: Leo Pharma Investigationel Site
city: Kyoto
country: Japan
facility: Leo Pharma Investigationel Site
city: Nagoya-shi
country: Japan
facility: Leo Pharma Investigationel Site
city: Obihiro
country: Japan
facility: Leo Pharma Investigationel Site
city: Osaka-fu
country: Japan
facility: Leo Pharma Investigationel Site
city: Osaka
country: Japan
facility: Leo Pharma Investigationel Site
city: Shimotsuke
country: Japan
facility: Leo Pharma Investigationel Site
city: Tokyo
country: Japan
facility: Leo Pharma Investigationel Site
city: Tokyo
country: Japan
facility: Leo Pharma Investigationel Site
city: Tokyo
country: Japan
facility: Leo Pharma Investigationel Site
city: Tokyo
country: Japan
facility: Leo Pharma Investigationel Site
city: Tsu
country: Japan
facility: Leo Pharma Investigationel Site
city: Yamanashi
country: Japan
facility: Leo Pharma Investigationel Site
city: Bergen Op Zoom
country: Netherlands
facility: Leo Pharma Investigationel Site
city: Breda
country: Netherlands
facility: Leo Pharma Investigationel Site
city: Groningen
country: Netherlands
facility: Leo Pharma Investigationel Site
city: Rotterdam
country: Netherlands
facility: Leo Pharma Investigationel Site
city: Kraków
country: Poland
facility: Leo Pharma Investigationel Site
city: Kraków
country: Poland
facility: Leo Pharma Investigationel Site
city: Kraków
country: Poland
facility: Leo Pharma Investigationel Site
city: Rzeszów
country: Poland
facility: Leo Pharma Investigationel Site
city: Swidnik
country: Poland
facility: Leo Pharma Investigationel Site
city: Wrocław
country: Poland
facility: Leo Pharma Investigationel Site
city: Wrocław
country: Poland
facility: Leo Pharma Investigationel Site
city: Wrocław
country: Poland
facility: Leo Pharma Investigationel Site
city: Łódź
country: Poland
facility: Leo Pharma Investigationel Site
city: Łódź
country: Poland
facility: Leo Pharma Investigationel Site
city: Glasgow
country: United Kingdom
facility: Leo Pharma Investigationel Site
city: London
country: United Kingdom
facility: Leo Pharma Investigationel Site
Study officials:
affiliation: LEO Pharma
name: Medical expert
role: STUDY_DIRECTOR
References:
citation: 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 Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial. JAMA Dermatol. 2023 Jun 1;159(6):596-605. doi: 10.1001/jamadermatol.2023.0627.
citation: Soehoel A, Larsen MS, Timmermann S. Population Pharmacokinetics of Tralokinumab in Adult Subjects With Moderate to Severe Atopic Dermatitis. Clin Pharmacol Drug Dev. 2022 Aug;11(8):910-921. doi: 10.1002/cpdd.1113. Epub 2022 Jun 7.