Investigation of Efficacy of Secukinumab in Patients With Moderate to Serve Atopic Dermatitis

Study Overview
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Brief Summary
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The overall aim of this study is to assess the effects of a new treatment called Secukinumab in adults suffering from moderate to severe atopic dermatitis. Furthermore, the study shall support the extension of the approval for Secukinumab from psoriasis to atopic dermatitis. The effectiveness of Secukinumab is determined on the reduction of the eczema score EASI 50 (Eczema Area and Severity Index, a tool to measure the severity of atopic dermatitis) at week 4.

Detailed Description
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Secukinumab is a humanized anti-IL-17A monoclonal antibody. Since Secukinumab is well established in the therapy of psoriasis with a highly favorable benefit to risk ration and IL-17 has been described in atopic dermatitis this study aims to investigate the effects of anti-IL-17 in atopic dermatitis. This is a randomized, placebo-controlled, multicenter, double-blinded study to evaluate the efficacy and safety of subcutaneous Secukinumab compared to placebo in 45 adults with atopic dermatitis. The study consists of 3 periods: a screening period of at least -14 days and up to -35 days, and a treatment period of 16 weeks and a follow-up period of additional 8 weeks. During the screening period eligibility of the patients is confirmed. Eligible patients are randomized 2:1 to treatment arm A or B at Day -7 (+2 to -15) during the randomization visit. Secukinumab (Cosentyx®) will be used according to the official label and SmPC (Summary of Product Characteristics). Patients in treatment arm A receive 300 mg Secukinumab administered as 2 subcutaneous injections of 150 mg (i.e. 2x 150 mg) at baseline day 1 and week 1, 2, 3, 4, 8, 12 and injections with placebo at week 5, 6, 7 and 16. For assessments of the study endpoints visits are performed at weeks 20 and 24. Placebo will be administered as 2 subcutaneous injections. Patients in treatment arm B receive placebo until visit 3 (week 3) and will switch to Secukinumab 300 mg s.c. up from visit 4 (week 4), visit 5, 6, 7, 8, 12 and16. For assessments of the study endpoints visits are performed at weeks 20 and 24.

Official Title
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A Randomized, Placebo-controlled, Double-blind Study to Scrutinize the Efficacy of Secukinumab in Patients With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis, Atopic, Eczema, Atopic, Neurodermatitis, Atopic

Intervention / Treatment
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* Drug: Secukinumab 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Atopic dermatitis (intrinsic disease without IgE mediated sensitization defined by negative history and negative SX-1 CAP FEIA or extrinsic disease defined by positive history and / or positive SX-1 CAP FEIA), SCORAD index score ≥ 25, EASI ≥ 16, Male and female patients at the age of 18 to 85 years, Signed Informed Consent, Subjects must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed, 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: Other inflammatory skin disease than atopic dermatitis, Use of cyclosporine, azathioprine, mycophenolate [wash-out period of 4 weeks]; Phototherapy (PUVA, NB-UVB, UVA1; [wash-out period of 2 weeks]), Dupilumab (Dupixent®; [wash-out period of 12 weeks]) Subjects expected to be exposed to an undue safety risk if participating in the trial including chronic infections, Contraindications of Secukinumab by label (i.e. approval for the treatment of psoriasis in the EU - refer to point 14 - 16 at the bottom of this section), Current severe progressive or uncontrolled disease which in the judgment of the investigator renders the subject unsuitable for the trial, Plans for administration of live vaccines during the study period, Chronic infection, Patients with instable chronic asthma, Any chronic inflammatory bowel disease (e.g. Crohn's disease), Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>10 mIU/mL), Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the study and for 20 weeks after stopping treatment. Effective contraception is defined as either: Barrier method: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicide (where available). Spermicides alone are not a barrier method of contraception and should not be used alone, The following methods are considered more effective than the barrier method and are also acceptable: Total abstinence: When this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception), Female sterilization: have had a surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, Male partner sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject, Use of established oral, injected or implanted hormonal methods of contraception, intrauterine device (IUD) or intrauterine system (IUS) NOTE: Women are considered post-menopausal and not of child bearing potential if they have had: i. 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or • six months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL Or ii. Surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening, Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit (a report ≤ 6 months is also accepted), History of alcohol or drug abuse within 1 year of the screening visit, Planned major surgical procedure during the patient's participation in this study, Hypersensitivity against Secukinumab, Active or reactive tuberculosis, Participation in other clinical studies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A<br>Patients in treatment arm A receive 300 mg Secukinumab administered as 2 subcutaneous injections of 150 mg (i.e. 2x 150 mg) at baseline day 1 and week 1, 2, 3, 4, 8, 12 and injections with placebo at week 5, 6, 7 and 16. For assessments of the study endpoints were followed up visits at week 20 and 24. Placebo will be administered as 2 subcutaneous injections. | Drug: Secukinumab 300 mg<br>* Solution for injection in pre-filled syringe<br>* Other names: COSENTYX ®;Drug: Placebo<br>* Solution for injection in pre-filled syringe<br>* Other names: Placebo (for Secukinumab);|
| Placebo Comparator: Treatment Arm B<br>Patients in treatment arm B receive placebo until visit 3 (week 3) and will switch to Secukinumab 300 mg s.c. up from visit 4 (week 4), visit 5, 6, 7, 8, 12 and16. For assessments of the study endpoints were followed up visits at week 20 and 24. | Drug: Secukinumab 300 mg<br>* Solution for injection in pre-filled syringe<br>* Other names: COSENTYX ®;Drug: Placebo<br>* Solution for injection in pre-filled syringe<br>* Other names: Placebo (for Secukinumab);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in EASI | Proportion of patients with a reduction of the eczema score EASI of at least 50%. The proportions are then compared between study arms. | week 4 (visit 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of EASI | To compare the proportions of patients with a reduction of the eczema score EASI 50. | baseline (day 1, visit 0) and End of Trial (Arm A week 12 / Arm B week 16) | 
| Reduction of EASI | To compare the number of patients with a reduction of the eczema score EASI 50. | Arm A week 12 / Arm B week 16 | 
| Reduction in SCORAD (Scoring atopic dermatitis) | The number of patients with a reduction of 50 % in SCORAD index. | day 1, week 4 and Arm A week 12 / Arm B week 16 | 
| Change in pruritus score (Visual Analogue Scale) | To compare the proportion of patients with change in pruritus score (VAS) by 50 %. | day 1, week 4 and Arm A week 12 / Arm B week 16 | 
| Change in IGA Score (5-point Investigator's Global Assessment) | To compare the proportion of patients who achieve a score of clear-0 or almost clear-1 in the static IGA score compared to baseline. | Arm A week 12 / Arm B week 16 | 
| Serum biomarkers CCL17 and CCL22 | To compare the serum biomarkers CCL17 and CCL22. | day 1, week 4 and Arm A week 12 / Arm B week 16 | 
| Increase in DLQI (Dermatology Life Quality Index) | To compare the proportion of patients achieving increase in DLQI by 30 %. | day 1, week 4 and Arm A week 12 / Arm B week 16 | 
| Consumption of topical methylprednisolone aceponate | To evaluate the quantification of the consumption of topical methylprednisolone aceponate 0.1% in gram. | day 1, week 4 and Arm A week 12 / Arm B week 16 | 
| Serious and non-serious adverse drug reactions | To observe any serious adverse drug reactions and non-serious adverse drug reactions. | treatment phase (day 1 up to week 16), follow-up phase (week 20, week 24) | 
| Gender distribution in patients with atopic dermatitis | Subgroup analyses will be performed to compare the effects of treatment with Secukinumab in male and female patients. Therefore, the recorded gender data will be used and separately analyzed for the above mentioned primary and secondary endpoints. | study arm A week 4 and both study arms week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurodermatitis, moderate to severe inflammatory reaction of the skin, Skin and Connective Tissue Diseases