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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Tralokinumab
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tralokinumab(Dose1) initial-> Tralokinumab(Dose1) maintenanceA<br>Week 0 to 16 (initial period): Tralokinumab (Dose 1) loading SC injection on Day 0 followed by tralokinumab (Dose 1) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 1) maintenance SC injection regimen A. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Tralokinumab(Dose1) initial-> Tralokinumab(Dose1) maintenanceB<br>Week 0 to 16 (initial period): Tralokinumab (Dose 1) loading SC injection on Day 0 followed by tralokinumab (Dose 1) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 1) maintenance SC injection regimen B. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Tralokinumab(Dose2) initial-> Tralokinumab(Dose2) maintenanceA<br>Week 0 to 16 (initial period): Tralokinumab (Dose 2) loading SC injection on Day 0 followed by tralokinumab (Dose 2) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 2) maintenance SC injection regimen A. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Tralokinumab(Dose2) initial-> Tralokinumab(Dose2) maintenanceB<br>Week 0 to 16 (initial period): Tralokinumab (Dose 2) loading SC injection on Day 0 followed by tralokinumab (Dose 2) injection regimen A. Week 16 to 52 (maintenance period): Tralokinumab (Dose 2) maintenance SC injection regimen B. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Placebo initial-> Placebo maintenance<br>Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 52 (maintenance period): Placebo continuation SC injection regimen A. | Drug: Placebos<br>* Placebo contains the same excipients in the same concentration only lacking tralokinumab.<br>* Other names: Placebo;|
| Experimental: Tralokinumab (Dose1) initial-> Open-label tralokinumab<br>Week 0 to 16 (initial period): Tralokinumab (Dose 1) loading SC injection on Day 0 followed by tralokinumab (Dose 1) injection regimen A. Week 16 to 52: Tralokinumab (Dose 1) maintenance SC regimen A - open-label with allowed use of topical corticosteroids | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Tralokinumab (Dose2) initial-> Open-label tralokinumab<br>Week 0 to 16 (initial period): Tralokinumab (Dose 2) loading SC injection on Day 0 followed by tralokinumab (Dose 2) injection regimen A. Week 16 to 52: Tralokinumab (Dose 1) maintenance SC regimen A - open-label with allowed use of topical corticosteroids | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Placebo initial-> Open-label tralokinumab<br>Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 52: Tralokinumab (Dose 1) maintenance SC regimen A - open-label with allowed use of topical corticosteroids | Drug: Tralokinumab<br>* 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.<br>Drug: Placebos<br>* Placebo contains the same excipients in the same concentration only lacking tralokinumab.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Presence of Anti-drug Antibodies | Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method. | From Week 0 to Week 16 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |