Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis

Study Overview
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Brief Summary
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Primary objective: To evaluate the efficacy of tralokinumab in combination with topical corticosteroids (TCS) compared with 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, health-related quality of life, and health care resource utilisation 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 16 weeks.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis Who Are Candidates for Systemic Therapy

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Tralokinumab
* Drug: Placebo
* Other: Topical corticosteroids (TCS)


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Japanese subject aged 18 years and above. Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD. History of AD for 1 year or more. A recent history (within 1 year before screening) of inadequate response to treatment with topical medication. AD involvement of 10% or more body surface area at screening and at baseline according to component A of SCORAD. Applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation. Key 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 or would interfere with assessment of treatment. Use of tanning beds or phototherapy within 6 weeks prior to randomisation. Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroids within 4 weeks prior to randomisation. Treatment with TCS, topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors, or topical Janus kinase inhibitors within 2 weeks prior to randomisation. Receipt of any marketed biological therapy (i.e. immunoglobulin, anti-immunoglobulin E) including dupilumab or investigational biologic agents 3 to 6 months prior to randomisation. Active skin infections 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: 18 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+TCS<br>Week 0 to Week 16: Tralokinumab will be given as subcutaneous injections. Participants will receive tralokinumab loading dose on Day 0 followed by multiple tralokinumab injections. The last administration will occur at Week 14. Topical corticosteroids (TCS) will be administered as needed. | Drug: Tralokinumab<br>* Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 subclass that specifically binds to human interleukin-13 (IL-13) and blocks the interaction with IL-13 receptors. It is presented as a liquid formulation for subcutaneous administration.<br>Other: Topical corticosteroids (TCS)<br>* TCS administered as needed.<br>|
| Placebo Comparator: Placebo+TCS<br>Week 0 to Week 16: Placebo will be given as subcutaneous injections. Participants will receive placebo loading dose on Day 0 followed by multiple placebo injections. The last administration will occur at Week 14. Topical corticosteroids (TCS) will be administered as needed. | Drug: Placebo<br>* Placebo contains the same excipients in the same concentration only lacking tralokinumab.<br>Other: Topical corticosteroids (TCS)<br>* TCS administered as needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | IGA is an instrument used in clinical trials to rate the severity of the participant's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). | Week 16 | 
| At Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 | Eczema Area and Severity Index (EASI) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition. | Week 0 to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Scoring Atopic Dermatitis (SCORAD) Total Score From Baseline to Week 16 | SCORAD is a validated tool to evaluate the AD disease based on 3 components: A) The extent of AD lesions. Assessed as percentage of each defined body area and reported as sum of all areas (max score = 100%). B) The severity of AD lesions. The intensity of 6 specific symptoms on a representative area was assessed using the scale: 0 = none/absent, 1 = mild, 2 = moderate, 3 = severe (max score = 18). C) Subjective symptoms. The itch and sleeplessness over the last 3 days/nights was recorded for each symptom by the subject on a VAS scale: 0 = no itch or trouble sleeping, 10 = unbearable itch or a lot of trouble sleeping (max score = 20). The SCORAD was calculated as: A/5+7B/2+C. The maximum total score is 103, with higher values indicating more severe disease. | Week 0 to Week 16 | 
| Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16. | DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their health-related quality of life over the past week, such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0=not at all ⁄ not relevant; 1=a little; 2=a lot; 3=very much). The total score is the sum of the 10 items (ranging from 0 to 30), with higher scores indicating poorer health-related quality of life. | Week 0 to Week 16 | 
| Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) Score (Weekly Average) of at Least 4 From Baseline to Week 16 | Participants assessed the itch for the past 24 hours using the Worst Daily Pruritus NRS, consisting of 11 points, with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. | Week 0 to Week 16 | 
| At Least 90% Reduction in EASI (EASI90) at Week 16 | EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition. | Week 0 to Week 16 | 
| At Least 50% Reduction in EASI (EASI50) at Week 16 | EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition. | Week 0 to Week 16 | 
| Percentage Change in EASI Score From Baseline to Week 16 | EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition. | Week 0 to Week 16 | 
| Change in Worst Daily Pruritus NRS Score (Weekly Average) From Baseline to Week 16 | Participants assessed the itch for the past 24 hours using the Worst Daily Pruritus NRS, consisting of 11 points, with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. | Week 0 to Week 16 | 
| Change in Eczema-related Sleep NRS Score (Weekly Average) From Baseline to Week 16 | Participants rated how much their eczema interfered with their sleep the last night using an 11-point NRS (0 indicating that it 'did not interfere' and 10 indicating that it 'completely interfered'). | Week 0 to Week 16 | 
| Change in Patient-Oriented Eczema Measure (POEM) Score Form Baseline to Week 16 | POEM consists of 7 items, each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness). Participants score how often they have experienced each symptom over the previous week, using 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 (ranging from 0 to 28) and reflects disease-related morbidity; higher scores indicate more severe disease. | Week 0 to Week 16 | 
| Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject | Number of events divided by patient years of exposure (= rate). | Week 0 to Week 16 | 
| Number of Subjects With Presence of Treatment-emergent Anti-drug Antibodies (ADA) From Baseline to Week 16 | Anti-tralokinumab antibody levels were analyzed using a validated bioanalytical method. Positive treatment-emergent ADA was defined as ADA negative or missing at baseline, and at least one positive post-baseline ADA response. Negative treatment-emergent ADA was defined as ADA negative or missing at baseline, and all post-baseline ADA assessments negative. | Week 0 to Week 16 |