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

Study Overview
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Brief Summary
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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.

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 Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Tralokinumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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(initial)responders-> Tralokinumab(continuation A)<br>Week 0 to 16 (initial period): Tralokinumab loading SC injection on Day 0 followed by tralokinumab injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen A. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Tralokinumab(initial)responders-> Tralokinumab(continuation B)<br>Week 0 to 16 (initial period): Tralokinumab loading SC injection on Day 0 followed by tralokinumab injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen B. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Tralokinumab(initial)non-respon-> Tralokinumab(continuation A)<br>Week 0 to 16 (initial period): Tralokinumab loading SC injection on Day 0 followed by tralokinumab injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen A. | Drug: Tralokinumab<br>* 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.<br>|
| Experimental: Placebo (initial)non-respon-> Tralokinumab(continuation A)<br>Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 32 (continuation period): Tralokinumab continuation SC injection regimen A. | Drug: Tralokinumab<br>* 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.<br>Drug: Placebo<br>* Placebo contains the same excipients in the same concentration only lacking tralokinumab.<br>|
| Placebo Comparator: Placebo(initial)responders-> Placebo(continuation A)<br>Week 0 to 16 (initial period): Placebo loading SC injection on Day 0 followed by placebo injection regimen A. Week 16 to 32 (continuation period): Placebo continuation SC injection regimen A. | Drug: Placebo<br>* Placebo contains the same excipients in the same concentration only lacking tralokinumab.<br>|

What is the study measuring?
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Primary Outcome Measures

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Number of Atopic Dermatitis Flares Through Week 16 | Assessed as appearance of new flares since previous visit. | Week 0 to Week 16 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |