A Study to Evaluate Safety and Effectiveness of Cendakimab (CC-93538) in Participants With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and safety of 3 dose regimen of CC-93538 in adult participants with moderate to severe Atopic Dermatitis (AD).

Official Title
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A Phase 2, Multicenter, Global, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Safety and Efficacy of Cendakimab (CC-93538) in Adult Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis, Atopic, Eczema

Intervention / Treatment
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* Drug: CC-93538
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must satisfy the following criteria to be enrolled in the study: Participant must be ≥ 18 years and ≤ 75 years of age and have a body weight of ≥ 40 kg (88.2 lb) at the time of signing the informed consent form (ICF). Participant has chronic atopic dermatitis (AD) as defined by Hanifin and Rajka that has been present for ≥ 1 year prior to the baseline visit (Day 1). Participant has moderate to severe, active, and symptomatic AD defined by meeting all of the following criteria on the day of the baseline visit (Day 1): Body Surface Area (BSA) ≥ 10%, and EASI score ≥ 16, and vIGA-AD ≥ 3, and Pruritus Numeric Rating Scale (NRS) severity score ≥ 4. Participant must have a documented history of inadequate response to treatment with topical medications for at least 4 weeks, unless topical treatments are otherwise medically inadvisable or has required systemic therapy for control of disease. Participant must be willing to apply a stable dose of topical emollient (eg, over-the-counter moisturizer, non-medicated emollient, etc.) twice daily for ≥ 7 days prior to the Baseline visit and continue application throughout the study. Participant must commit to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet light sources during the study. Participants currently receiving concomitant medications for any reason other than AD, such as inhaled corticosteroids, leukotriene receptor antagonists (eg, montelukast), or mast cell stabilizers (eg, cromolyn sodium) for asthma, must be on a stable regimen, which is defined as not starting a new drug, changing, or stopping dosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1 and through the treatment duration of the study. Female participants of childbearing potential must agree to practice a highly effective method of contraception. Exclusion Criteria: The presence of any of the following will exclude a participant from enrollment: Evidence of an active and/or concurrent inflammatory skin condition (eg, seborrheic dermatitis, psoriasis, acute allergic contact dermatitis, etc.) that would interfere with the Investigator or participant-driven evaluations of AD. Evidence of acute AD flare between the Screening and Baseline/ Randomization (eg, doubling of the EASI score between Screening and Baseline). Use of topical treatments that could affect the assessment of AD (eg, corticosteroids, calcineurin inhibitors, tars, antibiotic creams, topical antihistamines) within 7 days of the Day 1 visit. Received phototherapy narrowband UVB (NB-UVB) or broad band phototherapy within 4 weeks prior to the Baseline visit. Evidence of immunosuppression, participant is receiving, or has received systemic immunosuppressive or immunomodulating drugs (eg, azathioprine, cyclosporine, systemic corticosteroids, interferon gamma (IFN-γ), Janus kinase inhibitors, methotrexate, mycophenolate-mofetil, etc.) within 4 weeks prior to the Baseline visit. Treatment with immunomodulatory biologics Concurrent treatment with another IP Received a live attenuated vaccine within 1 month prior to the first Screening Visit or anticipates the need to be vaccinated with a live attenuated vaccine during the study. Active parasitic/helminthic infection or a suspected parasitic/helminthic infection. Ongoing infection A history of idiopathic anaphylaxis or a major immunologic reaction (such as anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an immunoglobulin G (IgG) containing agent. A known hypersensitivity to any ingredient in the investigational product (IP) is also exclusionary.

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 |
| --- | --- |
| Experimental: Dose 1: CC-93538 SC QW<br>Administration of CC-93538 Subcutaneous (SC) Once weekly (QW) for 16 weeks. | Drug: CC-93538<br>* Subcutaneous once weekly<br>* Other names: cendakimab;|
| Experimental: Dose 2: CC-93538 and Placebo SC Q2W<br>Starting at the baseline visit, active IP will be administered. On the alternate weeks, placebo will be administered to maintain the blind. | Drug: CC-93538<br>* Subcutaneous once weekly<br>* Other names: cendakimab;Other: Placebo<br>* Subcutaneous Every other week<br>|
| Experimental: Dose 3: CC-93538 and Placebo SC Q2W<br>Starting at the baseline visit, active IP and matching placebo will be administered. On the alternate weeks, placebo will be administered weekly to maintain the blind. | Drug: CC-93538<br>* Subcutaneous once weekly<br>* Other names: cendakimab;Other: Placebo<br>* Subcutaneous Every other week<br>|
| Placebo Comparator: Placebo SC QW<br>Administration of placebo each week. | Other: Placebo<br>* Subcutaneous Every other week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in EASI from Baseline at Week 16 | The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) | Up to week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with an vIGAAD score from Baseline at Week 16 | The Validated Investigator Global Assessment (vIGA)-AD is a validated 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded). | Up to week 16 | 
| Proportion of participants with at least a 75% improvement from Baseline in Eczema Area and Severity Index (EASI-75) at Week 16 | The EASI is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD. | Up to week 16 | 
| Percent change from Baseline in Pruritus Numerical Rating Scale (NRS) at Week 16 | Pruritus NRS is a single item, participant reported outcome (PRO) of itch severity. | Up to week 16 | 
| Proportion of participants with Pruritus NRS change of ≥ 4 points from Baseline at Week 16 | Pruritus NRS is a single item, participant reported outcome (PRO) of itch severity. | Up to week 16 | 
| Time to achieve at least 4 points of improvement in the severity of pruritus NRS scale in the first 16 weeks of treatment | Pruritus NRS is a single item, participant reported outcome (PRO) of itch severity. | Up to week 16 | 
| Proportion of participants with at least a 90% improvement from Baseline in Eczema Area and Severity Index (EASI-90) at Week 16 | The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) | Up to week 16 | 
| Mean change in SCORAD Scores from Baseline at Week 16 | The Scoring Atopic Dermatitis Index (SCORAD) is a validated scoring index for atopic dermatitis, which combines extent (0 to 100), severity (0 to 18), and subjective symptoms (0 to 20) based on pruritus and sleep loss, each scored (0 to 10). | Up to week 16 | 
| Percent change in BSA involved with AD from baseline at Week 16 | Percentage body surface area of the skin that displays signs or symptoms consistent with atopic dermatitis | Up to week 16 | 
| Incidence of Adverse Events (AEs) | An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. | Up to week 32 | 
| Assessment of Immunogenicity through measurement of serum concentrations of anti-drug antibodies to CC-93538 | Evaluated by the presence of anti-drug antibodies to CC-93538 | Up to week 32 | 
| Pharmacokinetics-Cthrough | Serum trough concentration of CC-93538 | Up to week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, Cendakimab, CC-93538