Tralokinumab in Combination With Topical Corticosteroids in Subjects With Severe Atopic Dermatitis - ECZTRA 7

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 severe AD in subjects who are not adequately controlled with or have contraindications to oral cyclosporine A (CSA). 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 to placebo in combination with TCS. To evaluate the safety of tralokinumab in combination with TCS when treating severe AD in subjects who are not adequately controlled with or have contraindications to oral CSA compared to placebo in combination with TCS.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre, Phase 3 Trial Investigating the Efficacy, Safety, and Tolerability of Tralokinumab Administered in Combination With Topical Corticosteroids to Adult Subjects With Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Tralokinumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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 or more Subjects with a history within 1 year prior to screening of inadequate response to treatment with topical medications or subjects for whom topical treatments are otherwise medically inadvisable AD involvement of 10% (or more) body surface area at screening and baseline (visit 3) according to component A of SCORAD Documented history of either no previous CSA exposure and not currently a candidate for CSA treatment OR previous exposure to CSA in which case CSA treatment should not be continued or restarted Subjects must have 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 TCSs are medically inadvisable in the opinion of the investigator Use of tanning beds or phototherapy (NBUVB, UVB, UVA1, PUVA), within 6 weeks prior to randomisation Treatment with immunomodulatory medications or bleach baths within 4 weeks prior to randomisation Treatment with topical phosphodiesterase-4 (PDE-4) inhibitor within 2 weeks prior to randomisation Receipt of any marketed or investigational biologic agent (e.g. cell-depleting agents or dupilumab) within 6 months prior to randomisation or until cell counts return to normal, whichever is longer History of any active skin infection within 1 week prior to randomisation History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to randomisation A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care History of any known primary immunodeficiency disorder including a positive HIV test at screening, or the subject taking antiretroviral medications

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>4 subcutaneous (SC) injections of tralokinumab 150 mg as a loading dose on Day 0, followed by 2 SC injections of tralokinumab 150 mg every 2 weeks (Q2W) regimen for 26 weeks. The last administration of the Investigational Medicinal Product (IMP) occurred at Week 24. From Day 0 to Week 24, a Topical corticosteroid (TCS) cream was dispensed to the participants at each IMP dosing visit (e.g., Q2W). Participants were instructed to treat active lesions as needed and to discontinue the TCS treatment when control was achieved. | 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>|
| Placebo Comparator: Placebo + TCS<br>4 subcutaneous (SC) injections of placebo as a loading dose on Day 0, followed by 2 SC injections of placebo every 2 weeks (Q2W) regimen for 26 weeks. The last administration of the Investigational Medicinal Product (IMP) occurred at Week 24. From Day 0 to Week 24, a Topical corticosteroid (TCS) cream was dispensed to the participants at each IMP dosing visit (e.g., Q2W). Participants were instructed to treat active lesions as needed and to discontinue the TCS treatment when control was achieved. | Other: 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 |
| --- | --- | --- |
| At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16 | EASI (Eczema Area and Severity Index) 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. | Week 0 to 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 Week 0 to Week 16 | Subjects will assess their worst itch severity over the past 24 hours using an 11-point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. | Week 0 to Week 16 | 
| Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16 | 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. | Week 0 to Week 16 | 
| Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16 | DLQI 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 different aspects of their health-related quality of life (HRQoL) over the last 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 (0 to 30); a high score is indicative of a poor HRQoL. | Week 0 to Week 16 | 
| 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 subject'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) From Week 0 to Week 26 | EASI (Eczema Area and Severity Index) 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. | Week 0 to Week 26 | 
| Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26 | Subjects will assess their worst itch severity over the past 24 hours using an 11-point numeric rating scale ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. | Week 0 to Week 26 | 
| Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26 | 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. | Week 0 to Week 26 | 
| Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26 | DLQI 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 different aspects of their health-related quality of life (HRQoL) over the last 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 (0 to 30); a high score is indicative of a poor HRQoL. | Week 0 to Week 26 | 
| Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26 | 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). | Week 26 | 
| Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Presence of ADA from Week 0 to Week 40 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. | Week 0 to Week 40 | 
| Number of Adverse Events From Week 0 to Week 40 | All adverse events are presented below under Adverse Events | Week 0 to Week 40 |