Study of Eblasakimab in Male or Female Moderate-to-Severe Atopic Dermatitis Patients Previously Treated With Dupilumab

Study Overview
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Brief Summary
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Multicenter, randomized, double-blind, placebo-controlled, parallel arm clinical study designed to evaluate the efficacy and safety of eblasakimab in participants with moderate-to-severe atopic dermatitis (AD) previously treated with dupilumab.The study consists of a 16-week treatment period and an 8-week follow-up period up to Week 24. Eligible participants will be randomized into one of the 2 treatment arms.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Eblasakimab in Male or Female Moderate-to-Severe Atopic Dermatitis Patients Previously Treated With Dupilumab

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Placebo
* Drug: ASLAN004


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ≥18 years Willing and able to comply with clinic visits and study-related procedures Chronic AD present for at least 1 year prior to screening Have vIGA score of ≥3 (scale of 1 to 4) at baseline Have ≥10% BSA of AD involvement at baseline Have EASI ≥16 at screening and baseline History of inadequate response to, intolerance to or contraindication to a stable regimen of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) as treatment for AD All participants must have previously been treated with dupilumab meeting one of the following conditions: Participants who stopped dupilumab treatment due to non-response, partial response, loss of efficacy must have been previously treated with dupilumab for at least 16 weeks duration; Participants who stopped dupilumab treatment due to intolerance or adverse events (AEs) to the drug may enter the study with no required prior length of dupilumab treatment; Participants who stopped dupilumab treatment due to cost or loss of access to dupilumab or for any other reasons may enter the study with no required prior length of dupilumab treatment; Exclusion Criteria: Use of immunosuppressive/immunomodulating drugs and/or therapies, JAK inhibitors, or phototherapy (including tanning booth/parlor) within 4 weeks prior to the Baseline visit Have an uncontrolled chronic disease that may require multiple intermittent use of systemic corticosteroids at Screening, as defined by the Investigator Have uncontrolled asthma that might require bursts of oral or systemic corticosteroids, or require either of the following due to ≥1 exacerbations within 12 months before Baseline: Systemic (oral and/or parenteral) corticosteroid treatment; Hospitalization for >24 hours; Have had systemic treatment with small molecule investigational drugs within 8 weeks or 5 half-lives (if known), whichever is longer, prior to the Baseline visit Have received treatment with topical corticosteroids (TCS), topical calcineurin inhibitors (TCI) such as tacrolimus and pimecrolimus, topical phosphodiesterase inhibitors such as crisaborole, topical JAK inhibitors (commercial or investigational use), within 1 week prior to randomization Have inadequate organ function or abnormal lab results considered clinically significant by the Investigator at the Screening visit History of human immunodeficiency virus (HIV) or positive HIV serology at Screening Infected with hepatitis B or hepatitis C viruses. For Hepatitis B, all subjects will undergo testing for Hepatitis B Surface Antigen (HBsAg) and Hepatitis B Core Antibody (HBcAb) during Screening. Subjects who are HBsAg positive are not eligible for the study. Subjects who are HBsAg negative and HBcAb positive will be tested for Hepatitis B Surface Antibody (HBsAb) and if HBsAb is positive, may be enrolled in the study; if HBsAb is negative, the subject is not eligible for the study. For Hepatitis C, all subjects will undergo testing for Hepatitis C antibody (HCVAb) during Screening. Subjects who are HCVAb positive are not eligible for the study. Active COVID-19 infection at Baseline. Have known liver cirrhosis and/or chronic hepatitis of any etiology Known diagnosis of active tuberculosis or non-tuberculous mycobacterial infection or latent tuberculosis unless it is well documented by a specialist that the patient has been adequately treated Allergen immunotherapy should be discontinued 6 months before randomization

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo loading dose equivalents at Baseline and Week 1, then placebo dose equivalents every 2 weeks (q2w) from Week 2 to Week 14 | Drug: Placebo<br>* Placebo Comparator<br>|
| Experimental: ASLAN004<br>Week 0, 1: LD of 600 mg; Week 2 through Week 15 QW: 400 mg dose | Drug: ASLAN004<br>* ASLAN004<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from Baseline in Eczema Area and Severity Index (EASI) at Week 16 | The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving validated Investigator's Global Assessment (vIGA) response of 0 (clear) or 1 (almost clear) at Week 16 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear) | Week 16 | 
| Proportion of participants with a 75% reduction Eczema Area and Severity Index 75 (EASI) | EASI scores range from 0 to 72 (severe)The EASI responder is defined as a participant who achieves a ≥75% improvement (EASI 75) from baseline in the EASI score | Week 16 | 
| Proportion of participants achieving EASI 50 | EASI scores range from 0 to 72 (severe)The EASI responder is defined as a participant who achieves a ≥50% improvement (EASI 50) from baseline in the EASI score | Week 16 | 
| Proportion of participants achieving EASI 90 | EASI scores range from 0 to 72 (severe)The EASI responder is defined as a participant who achieves a ≥90% improvement (EASI 90) from baseline in the EASI score | Week 16 | 
| Proportion of participants with EASI <7 | EASI scores range from 0 to 72 (severe) | Week 16 | 
| Absolute and percent change in peak Pruritus Numerical Rating Scale (P-NRS) | The P-NRS is an 11-point scale used by patients to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating the worst itch imaginable. Pruritus assessments will be recorded daily by the patient using an electronic diary | Week 16 and Week 24 | 
| Proportion of participants achieving a 4-point reduction in peak Pruritus Numerical Rating Scale | Pruritus Numerical Rating Scale | Week 16 | 
| Change in Body Surface Area (BSA) affected with AD | BSA ranges from 0% to 100 % with higher values representing greater extent of AD | Week 16 and Week 24 | 
| Change in SCORing Atopic Dermatitis (SCORAD) | The SCORAD is a validated measure of the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition | Week 16 and Week 24 | 
| Change in Dermatology Life Quality Index (DLQI) | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the patient's perception of the impact of AD disease symptoms and treatment on their quality of life (QoL). The 10 questions assess QoL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease). A high score is indicative of a poor QoL | Week 16 and Week 24 | 
| Change in Patient-Oriented Eczema Measure (POEM) | The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor QoL) | Week 16 and Week 24 | 
| Change in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | The EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranges from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine | Week 16 and Week 24 | 
| Absolute and percent change in sleep disturbance numerical rating scale (SD-NRS) | The SD-NRS is an 11-point scale used by patients to assess their sleep disturbance severity over the past 24 hours, with 0 indicating no or minimal sleep disturbance and 10 indicating the worst imaginable sleep disturbance. SD-NRS assessments will be recorded daily by the patient using an electronic diary | Week 16 and Week 24 | 
| Proportion of participants achieving a 4-point reduction in sleep disturbance numerical rating scale |  | Week 16 | 
| Percent change from baseline of validated Investigator's Global Assessment (vIGA) | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear) | Week 24 | 
| Percent change from baseline of Eczema Area and Severity Index | EASI scores range from 0 to 72 (severe) | Week 24 | 
| Number of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) from study drug administration |  | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atopic dermatitis, IL-13, ASLAN004, IL-13Rα1, Eczema, Anti-IL-13Rα1, atopic eczema