Study to Explore the Effect of Secukinumab, Compared to Placebo, on Fat Tissue and Skin in Plaque Psoriasis Patients

Study Overview
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Brief Summary
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This study provided a comparison of secukinumab to placebo with respect to skin inflammation as measured by skin exams in comparison to skin biopsies, adipose tissue and blood sample analyses.

Detailed Description
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This was a randomized, double-blind, placebo-controlled, multicenter design. Patients with moderate to severe plaque psoriasis received secukinumab 300 mg or placebo, with randomization stratified by body weight (< 90 kg, ≥ 90 kg). There were 5 periods to the study: Screening (1 to 4 weeks), Double-blind Treatment Period (12 weeks), Double-blind Induction Period (4 weeks), Open-label Treatment Period (36 weeks), and Follow-up Period (1 week). During the Double-blind Treatment Period, all patients attended study visits at Baseline, Weeks 1, 2, 3, 4, 8, and 12, and all doses of study treatment were self-administered at the study site. Patients underwent lesional (LS) and non-lesional (NL) skin biopsies at Baseline and Week 12. Assessments for the primary efficacy variable were performed at Week 12 before patients received their Week 12 dose. During the Double-blind Induction Period, patients randomized to placebo were switched to secukinumab 300 mg for the remainder of the study. K16 and skin histology/biomarkers were assessed from skin biopsies. The Psoriasis Assessment and Severity Index (PASI) and the Investigator's Global Assessment modified 2011 scale (IGA mod 2011) were performed at specified study visits. Safety was monitored by vital signs, weight, waist circumference, body mass index (BMI), and clinical laboratory tests (serum chemistry, hematology, highsensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), homeostatic assessment of insulin resistance (HOMA-IR), viral serology, serum and urine pregnancy).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Explore Changes in Subcutaneous Adipose Tissue and Modulation of Skin Inflammation After 12 Weeks of Treatment With Secukinumab, Compared to Placebo, and up to 52 Weeks of Treatment With Secukinumab in Adult Patients With Moderate to Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Biological: Secukinumab
* Biological: Placebo


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 Clinical diagnosis of chronic plaque-type psoriasis at least 6 months prior to randomization Moderate to severe plaque psoriasis as defined at baseline by: ≥10% Body Surface Area (BSA) involvement and PASI total score of ≥12 and IGA mod 2011 score of ≥3 (based on a scale of 0-4) Exclusion Criteria: Forms of diagnosed psoriasis other than chronic plaque psoriasis Medication-induced or medication exacerbated psoriasis Previous exposure to secukinumab or any other biologic drug directly targeting IL-17A or IL-17RA receptors Ongoing use of prohibited treatments Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab<br>Eligible patients received secukinumab 300 mg s.c. at randomization, Weeks 1, 2, 3 and 4 followed by monthly dosing up to Week 48 | Biological: Secukinumab<br>* Secukinumab 300 mg s.c. at randomization, Weeks 1, 2, 3, and 4 was followed by monthly dosing up to Week 48<br>* Other names: AIN457;|
| Placebo Comparator: Placebo<br>Eligible patients received placebo at randomization, Weeks 1, 2, 3, 4, and 8. At Week 12, patients were switched to treatment with secukinumab 300 mg s.c. at Weeks 12, 13, 14, 15, and 16 followed by monthly dosing up to Week 48 | Biological: Placebo<br>* Placebo s.c. at randomization, Weeks 1, 2, 3, 4, and 8; secukinumab 300 mg s.c. at Weeks 12, 13, 14, 15, and 16 followed by monthly dosing up to Week 48<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 12 | Response in skin histology/K16 expression to treatment (answered no) | 12 weeks | 
| Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12 | Psoriasis Area and Severity Index 90 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 52 | Response in skin histology/K16 expression to treatment (answered no) | 52 weeks | 
| Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 52 | Psoriasis Area and Severity Index 90 | 52 weeks | 
| Change in Systolic Blood Pressure From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 | baseline, Week 12 | 
| Change in Diastolic Blood Pressure From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 | baseline, Week 12 | 
| Change in Body Weight From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 | baseline, Week 12 | 
| Change in Glucose Level From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 | baseline, Week 12 | 
| Change in Insulin Level From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 | baseline, Week 12 | 
| Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 | baseline, Week 12 | 
| Change in Homeostatic Model Assessment of Insulin Resistance (UNIT) (HOMA-IR) From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to Week 12 Healthy Range: 1.0 (0.5-1.4) Less than 1.0 means you are insulin-sensitive which is optimal. Above 1.9 indicates early insulin resistance. Above 2.9 indicates significant insulin resistance. | baseline, Week 12 | 
| Change in Hemoglobin A1c (HbA1c) Test for Diabetes Score From Baseline to Week 12 | Vital signs: summary statistics for change from baseline to week 12 For people without diabetes, the normal range for the hemoglobin A1c level is between 4% and 5.6%. Hemoglobin A1c levels between 5.7% and 6.4% mean you have a higher chance of getting diabetes. Levels of 6.5% or higher mean you have diabetes. | baseline, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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secukinumab, scalp psoriasis, plaque psoriasis, AIN457, biologic, monoclonal antibod, psoriasis, AIN457A