Safety and Efficacy of Secukinumab in Mild Psoriasis

Study Overview
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Brief Summary
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Mild psoriasis not only progresses to moderate-to-severe psoriasis but also precedes systemic inflammation that leads to psoriatic arthritis and cardiovascular comorbidities. By curing mild psoriasis with a short-term anti- interleukin (IL)-17A treatment, investigators may reduce the costs of treating psoriasis and associated medical conditions, including psoriatic arthritis, cardiovascular disease, and diabetes.

Detailed Description
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Psoriasis is an immune-mediated disease of the skin that, even in mild disease, increases the risk of comorbidities such as cardiovascular disease and metabolic derangements. Mild psoriasis tends to be treated with topical drugs, while moderate-to-severe disease is optimally treated with systemic immune modulators. However, the treatment of mild psoriasis needs to be re-thought because recent studies have revealed that mild psoriasis is characterized by stronger expression of pathogenic molecules, such as interleukin (IL)-17A, and higher numbers of T cells in the skin, compared to severe psoriasis. A key distinction between mild and severe psoriasis is now discovered to be the higher expression of negative immune regulatory genes in mild lesions. Therefore, targeted immune therapy with anti-IL-17A, which is highly effective in severe psoriasis, might be equally (or even more) effective in mild disease. Also, restoration of immune tolerance might be more easily achieved in mild disease. Thus, short-term anti-IL-17A treatment of mild psoriasis might prevent the recurrence and eventually cure the disease. The aim of study is to test this hypothesis by exploring whether 3 months or 6 months of anti-IL17A treatment will prevent relapses after medication has been discontinued in mild psoriasis patients.

Official Title
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Safety and Efficacy of Secukinumab in Adults With Chronic Plaque Type Psoriasis With a PASI Score of 6 to 12

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Secukinumab
* Drug: Placebo followed by Secukinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed 18 years of age or older Chronic plaque-type psoriasis for at least 6 months Negative PPD (negative chest w-ray if positive) or negative QuantiFERON-TB Gold Have a PASI between 6 and 12 and Body Surface Area (BSA) affected by plaque-type psoriasis less than 10% at screening and baseline Willing to wash off steroid creams and ultraviolet B light (UVB) therapy for 2 weeks prior to the baseline visit Exclusion Criteria: Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular) Has previously received Secukinumab or other biologics History of Inflammatory Bowel Disease (IBD) History of Rheumatoid Arthritis Use of topical treatments for psoriasis, including steroids, vitamin D derivatives, vitamin A derivatives, salicylic acid, tar (except moisturizers) and/or ultraviolet A light (UVA)/UVB phototherapy within the last 2 weeks (if these have used them, the participant needs to wash off of them for at least 2 weeks after signing consent prior to baseline) Is pregnant, nursing, or planning a pregnancy (both men and women) within 5 months following the last administration of study drug Has recently received or is planning to receive a vaccination while on the study HIV positive Chronic untreated hepatitis C, positive hepatitis B surface antigen and acute hepatitis A infection Known tuberculosis (TB) or evidence of TB infection. Subjects with a positive QuantiFERON; TB test or a positive purified protein derivate (PPD) skin test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active TB. Any severe, progressive or uncontrolled medical condition at screening that in the judgment of the investigator prevents the subject from participating in the study.

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
Interventional Model Description: To compare the secukinumab-receiving mild psoriasis subjects (Group 1) and the placebo-receiving mild psoriasis subjects (Group 2).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>6 months of Secukinumab at a dose of 300 mg with injections administered once weekly at baseline and at weeks 1, 2, 3, and 4 and then every 4 weeks for 6 months of period. | Drug: Secukinumab<br>* Arms: Group 1 - Group 1 will receive Secukinumab at a dose of 300 mg with injections administered once weekly at baseline and at weeks 1, 2, 3, and 4 and then every 4 weeks for 6 months of period. In order to maintain the blind for the Group 2, Group 1 will receive placebo injections at weeks 13, 14, and 15. Group 1 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks).<br>* Other names: COSENTYX;|
| Placebo Comparator: Group 2<br>Placebo followed by Secukinumab. 3 months of placebo followed by 3 months of Secukinumab at a dose of 300 mg with injections administered once weekly at week 12 and at weeks 13, 14, 15, and 16 and then every 4 weeks for 3 months of period. | Drug: Placebo followed by Secukinumab<br>* Arms: Group 2 - Group 2 will receive placebo injections corresponding to the Group 1 regimen until week 8 in order to maintain a double-dummy design until week 12. From week 12, Group 2 will receive Secukinumab with injections administered once weekly at week 12 and at weeks 13, 14, 15, and 16 and then every 4 weeks for 3 months of period. Group 2 will discontinue Secukinumab after 6 months of period being observed from week 25 to week 72 (48 weeks).<br>* Other names: Placebo followed by COSENTYX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Have 75% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI75) | The percentage of subjects who have a reduction of 75% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 75). Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Have 90% or More Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI90) | The percentage of subjects who have a reduction of 90% or more from baseline in the Psoriasis Area and Severity Index (PASI) at week 12 (PASI 90). Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) | week 12 | 
| Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) Score of 0 or 1 With at Least a 2-step Improvement From Baseline (PGA 0/1 Response Rate). | Percentage of Subjects Who Achieve a Physician Global Assessment (PGA) score of 0 or 1 with at least a 2-step improvement from baseline (PGA 0/1 response rate). Physician Global Assessment (PGA) is a global assessment of all psoriasis lesions scored on a scale of 0-5, with 0 representing clear skin, 1 almost clear skin, and 5 representing severe psoriasis | week 12 | 
| Percentage of Subjects Who Experience Psoriasis Relapse | The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72. Psoriasis relapse is defined as loss of > 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) | week 24 through week 72 | 
| Percentage of Subjects Who Experience Severe Psoriasis Relapse | The percentage of subjects who experience a severe psoriasis relapse at any time between week 24 and week 72. Severe psoriasis relapse is defined as loss of > 75% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) | Observation Period: week 24 through week 72. | 
| Percentage of Subjects Who Experience Psoriasis Relapse After Psoriasis is Cleared | The percentage of subjects who experience a psoriasis relapse at any time between week 24 and week 72 among the subjects whose psoriasis is cleared between week 0 and week 24. Psoriasis relapse is defined as loss of > 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 24. Psoriasis clearance is defined as the achievement of PASI100, which is a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score. Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). | Observation Period: week 24 through week 72 | 
| Elapsed Time Until Relapse | Elapsed time from week 24 until relapse occurs before week 72, measured in weeks. | week 24 until week 72 | 
| Percentage of Subjects Who Have 100% Reduction in [Psoriasis Area-and-severity Index Score (PASI)] (PASI100) | The percentage of subjects who have a reduction of 100% from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI100) at week 12. Psoriasis Area and Severity Index (PASI) combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) | week 12 | 
| Frequency of Adverse Events | Frequency of all Adverse Events (AEs) including Serious Adverse Events (SAEs) that occur during the whole trial including the observational period (AEs and SAEs include but not limited to comorbidities, such as hypertension, diabetes, and cardiovascular diseases). | week 0 through week 72 | 
| Frequency of Serious Adverse Events | Frequency of Serious Adverse Events (SAEs) that occur during the whole trial including the observational period. | week 0 through week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Chronic Plaque Psoriasis, Secukinumab