Safety and Efficacy of Secukinumab Compared to Etanercept in Subjects With Moderate to Severe, Chronic Plaque-Type Psoriasis

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of secukinumab compared to placebo and etanercept in patients that have moderate to severe, chronic, plaque-type psoriasis.

Official Title
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A Randomized, Double-blind, Double-dummy, Placebo Controlled, Multicenter Study of Subcutaneous Secukinumab to Demonstrate Efficacy After Twelve Weeks of Treatment, Compared to Placebo and Etanercept, and to Assess the Safety, Tolerability and Long-term Efficacy up to One Year in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis

Conditions
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Chronic Plaque Psoriasis

Intervention / Treatment
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* Drug: Placebo
* Drug: secukinumab (AIN457)
* Drug: etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with chronic, plaque-type psoriasis for at least 6 months Must have moderate to severe psoriasis based on PASI greater than 12, IGA greater than 3, and greater than 10% body surface area Must be inadequately controlled by prior treatments (topicals, phototherapy, and/or systemic therapies) Exclusion Criteria: Forms of psoriasis other than chronic, plaque-type (such as pustular, erythrodermic and guttate psoriasis) Drug induced psoriasis Use of other psoriasis treatments during the study Prior use of etanercept Prior use of secukinumab or any other drug that target IL-17 (interleukin 17) or the IL-17 receptor Pregnant or lactating women; women who do not agree to use contraception during the study and for 16 weeks after stopping treatment Significant medical problems such as uncontrolled high blood pressure, congestive heart failure, etc. History of an ongoing, chronic or recurrent infection or evidence of tuberculosis Allergy to rubber or latex 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: AIN457 150mg<br>AIN457 150mg | Drug: Placebo<br>* Placebo to Match secukinumab (AIN457) 150mg or 300mg or Placebo to match etanercept<br>Drug: secukinumab (AIN457)<br>* secukinumab (AIN457) 150mg or 300mg subcutaneous<br>|
| Experimental: AIN457 300mg<br>AIN457 300mg | Drug: Placebo<br>* Placebo to Match secukinumab (AIN457) 150mg or 300mg or Placebo to match etanercept<br>Drug: secukinumab (AIN457)<br>* secukinumab (AIN457) 150mg or 300mg subcutaneous<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo to Match secukinumab (AIN457) 150mg or 300mg or Placebo to match etanercept<br>|
| Active Comparator: Etanercept<br>Etanercept | Drug: Placebo<br>* Placebo to Match secukinumab (AIN457) 150mg or 300mg or Placebo to match etanercept<br>Drug: etanercept<br>* etanercept 50mg subcutaneous<br>|
| Experimental: AIN457 150mg from Placebo<br>Patients randomized to AIN457 150mg in Maintenance phase when they were on Placebo in Induction Phase | Drug: Placebo<br>* Placebo to Match secukinumab (AIN457) 150mg or 300mg or Placebo to match etanercept<br>Drug: secukinumab (AIN457)<br>* secukinumab (AIN457) 150mg or 300mg subcutaneous<br>|
| Experimental: AIN457 300mg from Placebo<br>Patients randomized to AIN457 300mg in Maintenance phase when they were on Placebo in Induction Phase | Drug: Placebo<br>* Placebo to Match secukinumab (AIN457) 150mg or 300mg or Placebo to match etanercept<br>Drug: secukinumab (AIN457)<br>* secukinumab (AIN457) 150mg or 300mg subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Secukinumab Compared to Placebo in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure: PASI 75 (Psoriasis Area and Severity Index) . | A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis | 12 wks | 
| Efficacy of Secukinumab Compared to Placebo in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure:IGA (Investigator's Global Assessment) Mod 2011 With a 0 or 1 Response at Week 12 | The IGA mod 2011 scale has been developed based on a previous version of the scale used in secukinumab phase II studies in collaboration with health authorities, in particular the FDA. The explanations/descriptions of the points on the scale have been improved to ensure appropriate differentiation between the points. The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject's disease state at the time of the assessments, and does not attempt a comparison with any of the subject's previous disease states, whether at baseline or at a previous visit.IGA mod 2011 has a scale of 0-4 with the lower scores correlating to better performance. A score of 0= clear skin, 1= almost clear skin, 2=mild, 3=moderate,4=severe. | 12 wks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Secukinumab Compared to Etanercept and Placebo in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure: PASI 90 at Week 12 | A 90% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 90) is above current benchmark of primary endpoints for most clinical trials of psoriasis | 12 wks | 
| Efficacy of Secukinumab Compared to Etanercept in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure: PASI 75 at Week 12 | A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis | 12 wks | 
| Efficacy of Secukinumab Compared to Etanercept in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure: :IGA (Investigator's Global Assessment) Mod 2011 With a 0 or 1 Response at Week 12 | The IGA mod 2011 scale has been developed based on a previous version of the scale used in secukinumab phase II studies in collaboration with health authorities, in particular the FDA. The explanations/descriptions of the points on the scale have been improved to ensure appropriate differentiation between the points. The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject's disease state at the time of the assessments, and does not attempt a comparison with any of the subject's previous disease states, whether at baseline or at a previous visit.IGA mod 2011 has a scale of 0-4 with the lower scores correlating to better performance. A score of 0= clear skin, 1= almost clear skin, 2=mild, 3=moderate,4=severe. | 12 wks | 
| Maintenance of PASI 75 Response at Week 52 for Patients Who Were PASI 75 Responders at Week 12 (Non-responder Imputation) |  | 52 wks | 
| Maintenance of IGA Mod 2011 0 or 1 Response After 52 Weeks of Treatment for Subjects Who Were IGA Mod 2011 0 or 1 Responders After 12 Weeks of Treatment |  | 52 wks | 
| Change in Score From Baseline to Week 12 in Psoriasis Symptom Diary Items Itching, Pain and Scaling in AIN457 vs Placebo | The Psoriasis Symptom Diary©, a 16-item patient reported outcome (PRO) measure developed and validated in accordance with the FDA PRO Guidance (FDA Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, 2009), demonstrated favorable psychometric properties and usefulness for treatment efficacy evaluation alongside other measures of disease severity in clinical trials for chronic plaque psoriasis.Weekly averages will be derived for each of the 16 questions of the Psoriasis Diary up to Week 12. A weekly average is the sum of the scored item over the course of the study week divided by the number of days on which the item was completed and will be set to missing if four or more daily assessments were missing of the corresponding question. The range for each question is 0 to 10 with the higher score depicting a more progressed disease state. A reduction in score from baseline shows efficacy | baseline to week 12 | 
| Change From Baseline to Week 12 in Psoriasis Symptom Diary Items Itching, Pain and Scaling in AIN457 vs Etanercept | The Psoriasis Symptom Diary©, a 16-item patient reported outcome (PRO) measure developed and validated in accordance with the FDA PRO Guidance (FDA Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, 2009), demonstrated favorable psychometric properties and usefulness for treatment efficacy evaluation alongside other measures of disease severity in clinical trials for chronic plaque psoriasis.Weekly averages will be derived for each of the 16 questions of the Psoriasis Diary up to Week 12. A weekly average is the sum of the scored item over the course of the study week divided by the number of days on which the item was completed and will be set to missing if four or more daily assessments were missing of the corresponding question. The range for each question is 0 to 10 with the higher score depicting a more progressed disease state. A reduction in score from baseline shows efficacy | baseline to week 12 | 
| Number of Participants Developing Anti-secukinumab Antibodies | Describes the number of participants tested positive for anti-secukinumab antibodies. It refers to the number of patients who had no positive values at baseline but developed them only after start of active study treatment (AIN457 or etanercept) | 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis,, inflammatory skin disease,, scaly patches, Psoriasis, inflammatory skin disease