Efficacy, Safety, and Pharmacokinetic Profile of Etokimab (ANB020) in Adult Participants With Moderate-to-Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy, safety, and pharmacokinetic (PK) profiles of multiple doses of etokimab in adult participants with atopic dermatitis (AD).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study Investigating the Efficacy, Safety, and Pharmacokinetic Profile of ANB020 Administered to Adult Subjects With Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: Etokimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants must be 18 to 75 years of age, at the time of signing the informed consent. Body mass index (BMI) of 18 to ≤ 35 kilogram per square meter (kg/m^2) at screening. Clinically confirmed diagnosis of AD. Eczema Area and Severity Index (EASI) score ≥ 16, body surface area (BSA) involvement ≥ 10%, and an Investigator's Global Assessment (IGA) score (5-point scale) ≥ 3 at baseline. Participants with a history of inadequate response to topical treatment, use of systemic treatments to treat AD, and/or for whom topical treatments are otherwise medically inadvisable. Daily use of non-medicated emollient for at least 7 days prior to baseline. Exclusion Criteria: Treatment with topical corticosteroids, topical calcineurin inhibitors, or crisaborole within 2 weeks before dosing. Prior exposure to an anti-interleukin (IL)-33 antibody. Exposure to an investigational or licensed or other anti T-helper 2 (Th2) type cytokine or cytokine receptor antagonist within 16 weeks or 5 half-lives, whichever is longer. History of prior exposure to any investigational or biologic systemic treatment within 5 half lives of the screening or is currently enrolled in another clinical study. Have received systemic treatment for AD (including systemic corticosteroids, immunosuppressants or immunomodulating drugs, or phototherapy or use of a tanning booth) within 4 weeks before screening. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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>Participants received matching placebo to etokimab, administered subcutaneously (SC) every 4 weeks (Q4W) for up to 16 weeks. | Drug: Placebo<br>* Administered by subcutaneous injection<br>|
| Experimental: Etokimab 20 mg SC Q4W<br>Participants received etokimab 20 milligrams (mg) administered SC Q4W for up to 16 weeks. | Biological: Etokimab<br>* Humanized monoclonal antibody, administered by subcutaneous injection<br>* Other names: ANB020;|
| Experimental: Etokimab 300 mg load + 150 mg SC Q8W<br>Participants received a 300 mg loading dose of etokimab on Day 1 then 150 mg etokimab administered SC every 8 weeks (Q8W) for up to 16 weeks. At Weeks 4 and 12 participants received placebo. | Biological: Etokimab<br>* Humanized monoclonal antibody, administered by subcutaneous injection<br>* Other names: ANB020;Drug: Placebo<br>* Administered by subcutaneous injection<br>|
| Experimental: Etokimab 300 mg load + 150 mg SC Q4W<br>Participants received a 300 mg loading dose of etokimab on Day 1 then 150 mg etokimab administered SC Q4W for up to 16 weeks. | Biological: Etokimab<br>* Humanized monoclonal antibody, administered by subcutaneous injection<br>* Other names: ANB020;|
| Experimental: Etokimab 600 mg load + 300 mg SC Q4W<br>Participants received a 600 mg loading dose of etokimab on Day 1 then 300 mg etokimab administered SC Q4W for up to 16 weeks. | Biological: Etokimab<br>* Humanized monoclonal antibody, administered by subcutaneous injection<br>* Other names: ANB020;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none [0], mild [1], moderate [2], or severe [3]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none [0], mild [1], moderate [2], or severe [3]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). | Baseline and Week 16 | 
| Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none [0], mild [1], moderate [2], or severe [3]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). | Baseline and Week 16 | 
| Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none [0], mild [1], moderate [2], or severe [3]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). | Baseline and Week 16 | 
| Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | The vIGA-AD is a static 5-point scale to evaluate AD severity globally: 0: Clear - No inflammatory signs of AD (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Postinflammatory hyperpigmentation and/or hypopigmentation may be present Almost clear - Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread in extent. Oozing or crusting may be present. Number of participants with ≥2 points reduction in vIGA-AD is presented. | Baseline and Week 16 | 
| Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | vIGA-AD is static 5-point scale to evaluate AD severity globally: 0: Clear - No inflammatory signs of AD (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Postinflammatory hyperpigmentation and/or hypopigmentation may be present Almost clear - Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread. Oozing or crusting may be present Participants who achieved vIGA-AD response of 0 (clear) or 1 (almost clear) are reported. | Week 16 | 
| Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | Participants were asked to rate itch (pruritis) intensity at its worst (peak) during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch) in a daily electronic diary. Weekly average was calculated as the average of the 7 days before each visit. | Baseline and Week 16 | 
| Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | Participants were asked to rate itch (pruritis) intensity at its worst (peak) during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch) in a daily electronic diary. Weekly average was calculated as the average of the 7 days before each visit. | Baseline and Week 16 | 
| Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as extent of disease (0 [no disease]-102 [worst disease]). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 (none) to 18 (severe intensity). Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (itch: 0 [no itch] to 10 [worst imaginable itch] and sleeplessness: 0 [no sleeplessness] to 10 [worst imaginable sleeplessness]) (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 (no AD present) to 103.4 (worst). | Baseline and Week 16 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much). Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A negative change from Baseline indicates improvement. | Baseline and Week 16 | 
| Number of Participants Who Experienced an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent adverse event (TEAE) is any AE that started or worsened in severity on or after the date and time of the study drug administration. A serious adverse event (SAE) is as any untoward medical occurrence that, at any dose: Resulted in death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent disability/incapacity; Was a congenital anomaly/birth defect. | From first dose to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ANB020, etokimab, eczema, moderate to severe