A Study to Assess Subcutaneous Lirentelimab (AK002) in Atopic Dermatitis

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous lirentelimab (AK002), given every 2 weeks for 7 doses, in adult subjects with moderate-to-severe AD inadequately controlled by topical treatments. Subjects who complete the randomized, double-blind, placebo-controlled treatment period may have the option to enroll in an open-label extension period and receive up to 7 doses of subcutaneous lirentelimab.

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Subcutaneous Lirentelimab in Adult Subjects With Moderate-to-Severe Atopic Dermatitis Inadequately Controlled by Topical Treatments

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: AK002
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject is able to understand the information on the study, has the capacity to consent, and has provided written informed consent. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent form. Chronic AD (as defined by the American Academy of Dermatology Consensus Criteria) (Eichenfield, 2014) that has been present for at least 3 years before the screening visit. Documented recent history of inadequate response to treatment with topical medications such as topical corticosteroids, calcineurin inhibitors, JAK inhibitors, or PDE4 inhibitors (crisaborole) for at least 4 weeks in the 6 months prior to screening, or subjects for whom these topical treatments are otherwise medically inadvisable (e.g., because of side effects or safety risks). Subjects who are biologic naive or biologic-exposed. Biologic-exposed includes patients who have demonstrated secondary loss of response, intolerance, or lack of continued access to biologics due to economic reasons. EASI score of ≥16 at screening and at baseline. Involvement of at least 10% or more of BSA at screening and at baseline. An IGA score of 3 or above on a scale from 0-4 at screening and at baseline. The subject should have applied a stable dose of non-medicated, non-prescription, topical emollient at least twice daily for 7 consecutive days immediately before the baseline visit. Key Exclusion Criteria: Current use of biologics for any indication. Demonstrated lack of primary response to treatment with a biologic for the treatment of AD defined as no response to treatment despite complete adherence to the prescribed regimen for at least 3 months (primary non-responders). Use of any of the following treatments within 4 weeks prior to the baseline visit or any condition that in the opinion of the Investigator is likely to require such treatment(s) during the first 4 weeks of study treatment: (i) phototherapy for AD; (ii) immunosuppressive or immunomodulatory drugs, including but not limited to systemic calcineurin inhibitors (e.g., cyclosporin, tacrolimus), mTOR inhibitors (e.g., sirolimus, everolimus), anti-metabolites (e.g., azathioprine, methotrexate, 6-mercaptopurine, leflunomide, mycophenolate mofetil), alkylating agents (e.g., cyclophosphamide), TNF inhibitors (e.g., infliximab, adalimumab), eosinophil depleting drugs (e.g., pramipexole), and systemic corticosteroids; (iii) oral JAK inhibitors within 8 weeks of the baseline visit. Treatment with biologics: (i) any cell-depleting agents including but not limited to rituximab within 6 months prior to the baseline visit or until lymphocyte count returns to normal, whichever is longer; (ii) other biologics (e.g., dupilumab, omalizumab, etc) within 5 half-lives, if known, or 8 weeks prior to baseline visit, whichever is longer. Use of any topical corticosteroids, topical calcineurin inhibitors, topical JAK inhibitors (e.g., ruxolitinib), or topical PDE4 inhibitors (crisaborole) for the treatment of AD within 1 week prior to the baseline visit. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit. Treatment with chemotherapy or radiotherapy in the preceding 6 months. Presence of skin comorbidities/concomitant conditions that may interfere with study assessments or interpretation of study results. Planned or anticipated use of any prohibited medications. History of malignancy except carcinoma in situ in the cervix, early-stage prostate cancer, or non-melanoma skin cancers. Any disease, condition (medical or surgical), or cardiac abnormality that in the opinion of the Investigator would place the subject at increased risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Lirentelimab (AK002) SC 300 mg<br>Subjects in this arm will receive 7 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks. | Drug: AK002<br>* Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1)monoclonal antibody directed against Siglec-8<br>* Other names: Lirentelimab;|
| Other: Placebo<br>Placebo | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who achieve 75% improvement on the Eczema Area and Severity Index (EASI-75) at Week 14 |  | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in EASI from baseline to Week 14 |  | Baseline to Week 14 | 
| Proportion of subjects achieving an IGA score of 0 or 1 and a 2-point improvement at Week 14 vs baseline |  | Baseline to Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AD, Dermatitis, Eczema