Secukinumab for Treatment of Atopic Dermatitis

Study Overview
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Brief Summary
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Atopic Dermatitis, also known as atopic eczema, or eczema, is a common skin disease that can affect males and females of all ages, but often starts in childhood. Recent studies show at least 4-7% of adults and 15-25% of children to be affected, with one third of patients having severe disease. It results in very itchy, red, swollen, and cracked skin. Scratching worsens the symptoms and causes the skin to become thickened over time. Patients with atopic dermatitis have an increased risk of skin infections, and many also develop hay fever or asthma. Atopic dermatitis can cause significant distress to both patients and their families. In this study, the aim is to assess the effects of a new treatment called secukinumab in patients with atopic dermatitis. A total of 30 patients will be included in the study, which will run for a total of 52 weeks.

Detailed Description
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This is a randomized, double-blind, pilot study of a total of 44 subjects with AD (22 with intrinsic and 22 with extrinsic AD) consisting of 2 phases. Subjects will be randomized (2:1) to either receive secukinumab 300 mg or placebo via subcutaneous injection using 2 prefilled syringes.

Official Title
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A Pilot Study to Evaluate the Efficacy and Safety of Secukinumab in the Treatment of Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Secukinumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject at least 18 years of age If female, the subject is not pregnant or nursing Subject is able to provide written informed consent and comply with the requirements of this study protocol. Chronic (>6 months) atopic dermatitis (intrinsic disease with IgE levels that are below 200, and extrinsic disease with IgE levels above 200). Moderate to severe AD (SCORAD index ≥25, and IGA index≥3). Subjects who are women of childbearing potential must have a negative urine pregnancy test at screening and must be practicing an adequate, medically acceptable method of birth control for at least 30 days before Day 0 and at least 6 months after the last study drug administration. Acceptable methods of birth control include intrauterine device (IUD); oral, transdermal, implanted or injected hormonal contraceptives (must have been initiated at least 1 month before entering the study); tubal ligation; abstinence and barrier methods with spermicide. Otherwise, if not of childbearing potential, subjects must: have a sterile or vasectomized partner; have had a hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in a menopausal state for at least a year. Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) negative at the time of screening, or if patient has a history of positive PPD or QuantiFERON, he/she has completed the appropriate prophylaxis. Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, and physical examination. Patients with stable chronic asthma, treated with inhaled corticosteroids, will be allowed to participate. Exclusion Criteria: Male or female subject at least 18 years of age If female, the subject is not pregnant or nursing Subject is able to provide written informed consent and comply with the requirements of this study protocol. Chronic (>6 months) atopic dermatitis (intrinsic disease with IgE levels that are below 200, and extrinsic disease with IgE levels above 200). Moderate to severe AD (SCORAD index ≥25, and IGA index≥3). Subjects who are women of childbearing potential must have a negative urine pregnancy test at screening and must be practicing an adequate, medically acceptable method of birth control for at least 30 days before Day 0 and at least 6 months after the last study drug administration. Acceptable methods of birth control include intrauterine device (IUD); oral, transdermal, implanted or injected hormonal contraceptives (must have been initiated at least 1 month before entering the study); tubal ligation; abstinence and barrier methods with spermicide. Otherwise, if not of childbearing potential, subjects must: have a sterile or vasectomized partner; have had a hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in a menopausal state for at least a year. Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) negative at the time of screening, or if patient has a history of positive PPD or QuantiFERON, he/she has completed the appropriate prophylaxis. Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, and physical examination. Patients with stable chronic asthma, treated with inhaled corticosteroids, will be allowed to participate.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab<br>Secukinumab (300 mg) via subcutaneous injection using 2 prefilled syringes | Drug: Secukinumab<br>* At Weeks 0, 1, 2, 3, 4 and every 2 weeks thereafter through and including Week 12 in phase 1 of the study.<br>|
| Placebo Comparator: Placebo<br>Placebo via subcutaneous injection using 2 prefilled syringes | Drug: Placebo<br>* At Weeks 0, 1, 2, 3, 4 and every 2 weeks thereafter through and including Week 12 in phase 1 of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold-Change in Epidermal Thickness of Lesional Skin | Epidermal hyperplasia assessed using change in epidermal thickness at week 16 as compared to baseline | at Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fold-Change in K16 Expression of Lesional Skin | Epidermal hyperplasia assessed using change in the epidermal proliferation marker Ki67 at week 16 as compared to baseline. Staining quantification was performed with ImageJ 1.42 | at Week 16 | 
| Number of Patients With SCORAD-50 | The proportion of patients who achieve an improvement of 50% or greater from their Baseline objective SCORAD up to week 52. SCORing Atopic Dermatitis (SCORAD) -The intensity part of the SCORAD index consists of six items: erythema, edema⁄papulation, excoriations, lichenification, oozing⁄crusts and dryness. Each item graded on a scale 0-3. The subjective items include daily pruritus and sleeplessness, graded on a 10-cm visual analogue scale, with maximum subjective score 20. SCORAD full score is 0-103, with higher score indicating more symptoms. | Week 4, Week 16, Week 32, Week 52 | 
| Number of Patients Who Achieve EASI-50 Score | The proportion of patients who achieve an improvement of 50% or greater from their Baseline EASI score up to week 52. The EASI index assigns proportionate values to 4 body regions. Each region is assigned a score of 0 to 3, indicating none, mild, moderate, and severe clinical expression. The percentage of area involved is also assigned an eruption proportional score from 0 to 6. The total body score for each body region is obtained by multiplying the sum of the severity scores by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gives the EASI total from 0-72, with higher score indicating more severity. | Week 4, Week 16, Week 32, Week 52 | 
| Number of Patients With Static Investigator's Global Assessment (IGA) Score 0 or 1 | The proportion of patients who achieve a score of clear-0 or almost clear-1 in the static IGA score at Week 16 as compared to Baseline. The static IGA score represents an overall static evaluation of dermatitis, performed by the investigator at each visit. It utilizes a scale of 6-points; total scale ranging from 0 (clear) to 5 (very severe disease). | Week 16, Week 32, Week 52 | 
| Percentage Change From Baseline in SCORAD Score | Percentage change in SCORAD scores at Week 16 as compared to baseline. SCORing Atopic Dermatitis (SCORAD) full score is 0-103, with higher score indicating more symptoms. | at Week 16 | 
| Percentage Change From Baseline in EASI Scores | Percentage change in EASI scores at Week 16 as compared to baseline. Eczema Area and Severity Index (EASI) total score from 0-72, with higher score indicating more severity. | at Week 16 | 
| Fold-Change in Elafin/Pi3 Level From Baseline | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of elafin/Pi3 at week 16 as compared to baseline | at Week 16 | 
| Fold-Change in CCL20 Level | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of CCL20 at week 16 as compared to baseline. | at Week 16 | 
| Fold-Change in CXCL1 Level | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of CXCL1 at week 16 as compared to baseline. | at Week 16 | 
| Fold-Change in S100A7 Level | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of S100A7 at week 16 as compared to baseline. | at Week 16 | 
| Fold-Change in A8 Level | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of A8 at week 16 as compared to baseline | at Week 16 | 
| Fold-Change in A9 Level | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of A9 at Week 16 as compared to baseline. | at Week 16 | 
| Fold-Change in A12 Level | Change of IL-17 regulated keratinocyte products assessed by a change of the mRNA gene expression levels of A12 as compared to baseline | at Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic dermatitis, extrinsic atopic dermatitis, intrinsic atopic dermatitis