Efficacy and Safety of Subcutaneous Secukinumab (AIN457) for Moderate to Severe Chronic Plaque-type Psoriasis Assessing Different Doses and Dose Regimens

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety and efficacy of two different doses and two different dose regimens of subcutaneous secukinumab in patients that have moderate to severe, chronic, plaque-type psoriasis.

Official Title
-----------------
A Randomized, Double-blind, Multicenter Study of Subcutaneous Secukinumab, Assessing Psoriasis Area and Severity Index (PASI) Response and Maintenance of Response in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis on Either a Fixed Dose Regimen or on a Retreatment at Start of Relapse Regimen

Conditions
-----------------
Moderate to Severe Plaque-type Psoriasis

Intervention / Treatment
-----------------
* Drug: AIN457 150mg
* Drug: AIN457 300mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Moderate and severe plaque-type psoriasis diagnosed for at least 6 months. Severity of disease meeting all of the following three criteria: PASI score of 12 or greater, Investigator's Global Assessment (IGA) score of 3 or greater Total body surface area (BSA) affected of 10% or greater. Inadequate control by prior use of topical treatment, phototherapy and/or systemic therapy. Exclusion criteria: Current forms of psoriasis other than chronic plaque-type psoriasis (for example, pustular, erythrodermic, guttate). Current drug-induced psoriasis. Previous use of secukinumab or any drug that targets IL-17 or IL-17 receptor. Significant medical problems such as uncontrolled hypertension, congestive heart failure or a condition that significantly immunocompromises the subject. Hematological abnormalities. History of an ongoing, chronic or recurrent infectious disease, or evidence of untreated tuberculosis. History of lymphoproliferative disease or history of malignancy of any organ system within the past 5 years. Pregnant or nursing (lactating) women. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIN457150 mg- Induction period Only(IPO)<br>secukinumab 150 mg (1 injection per dose) and placebo to secukinumab 150 mg (1 injection per dose). Induction period only (IPO) | Drug: AIN457 150mg<br>* (1 injection per dose) and placebo to secukinumab 150 mg<br>* Other names: secukinumab 150 mg;|
| Experimental: AIN457 300 mg - IPO<br>secukinumab- 2 x 150mg injections per dose | Drug: AIN457 300mg<br>* secukinumab 150 mg (2 injections per dose)<br>* Other names: secukinumab;|
| Experimental: AIN457 150 mg - Fixed Interval (FI)<br>1 s.c. secukinumab 150 mg injection + 1 s.c. PBO (placebo) secukinumab injection | Drug: AIN457 150mg<br>* (1 injection per dose) and placebo to secukinumab 150 mg<br>* Other names: secukinumab 150 mg;|
| Experimental: AIN457 300 mg FI<br>2 s.c. secukinumab 150 mg injections | Drug: AIN457 300mg<br>* secukinumab 150 mg (2 injections per dose)<br>* Other names: secukinumab;|
| Experimental: AIN457 150 mg- Start of relapse (SoR)<br>1 s.c. secukinumab 150 mg injection + 1 s.c. PBO secukinumab injection | Drug: AIN457 150mg<br>* (1 injection per dose) and placebo to secukinumab 150 mg<br>* Other names: secukinumab 150 mg;|
| Experimental: AIN457 300 mg- SoR<br>2 s.c. secukinumab 150 mg injections | Drug: AIN457 300mg<br>* secukinumab 150 mg (2 injections per dose)<br>* Other names: secukinumab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For the Fixed Interval Group and the Start of Relapse (SoR) Group, the Percentage of Participants (Who Responded to Treatment at Week 12) Maintaining a 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 52 | PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head: 0.1, arms: 0.2 body: 0.3 legs: 0.4) | Week 40 , week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline for PASI 50 / 75 / 90 / 100 and IGA 2011 Score of 0 or 1 at Week 2, 4, 6, 8, 12 | PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head:01, arms:0.2 body:0.3 legs:0.4) | Baseline, week 2, 3 , 4, 8, 12 | 
| Absolute Change From Baseline for PASI 50 / 75 / 90 / 100 and IGA 2011 Score of 0 or 1 at Week at Week 16, 20, 24,28,32,36,40,44,48,and Week 52 | PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section(head:01, arms:0.2 body:0.3 legs:0.4) | Baseline, week 12,16,20,24,28,32,36,40,44,48 and week 52 | 
| Percent of Participants Achieving Psoriasis Area & Severity Index (PASI) Score and IGA Mod 2011 0 or 1 Score Over Time at Week 12 and 52 (Induction) | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe | Baseline, week 2, 4, 6, 8, 12 | 
| Percent of Participants Achieving Psoriasis Area & Severity Index (PASI) Score and IGA Mod 2011 0 or 1 Score Over Time at Week 12 and 52 (Maintenance Period)) | The IGA mod 2011 is a static scale, i.e., it refers exclusively to the participant's disease state at the time of the assessments and does not attempt a comparison to any of the participant's previous disease states at prior visits. The score ranges from 0 (clear) to 4 (severe. The score 0 is clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 is severe | Baseline, week 16,20,24,28,32,36,40,44,48, and Week 52 | 
| Change From Baseline in EQ-5D at Each Visit, up to Week 52, (Induction) | ED-5Q: Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Five domains are assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with three possible score: 1 indicates no problems, better state of health; 3 indicates worst state of health (example confined to bed) A visual analog scale (VAS) assesses the health status from 0 (worst possible health state) to 100 (best possible health state) | Baseline to week 2, 4, 8, 12 | 
| Change From Baseline in EQ-5D at Each Visit, up to Week 52, (Maintenance) | ED-5Q: Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Five domains are assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with three possible score: 1 indicates no problems, better state of health; 3 indicates worst state of health (example confined to bed) A visual analog scale (VAS) assesses the health status from 0 (worst possible health state) to 100 (best possible health state) | Baseline to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52. | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score. up to Week 52, (Induction) | The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). Not relevant is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions | Baseline to week 2, 4, 8, 12 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score. up to Week 52, (Maintenance) | The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). Not relevant is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions | Baseline to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52. | 
| % of Participants Achieving a DLQI Score of 0 or 1 at Each Visit up to Week 52, (Induction) | The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). Not relevant is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions | Baseline to week 2, 4, 6, 8, 12 | 
| % of Participants Achieving a DLQI Score of 0 or 1 at Each Visit up to Week 52, (Maintenance). | The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). Not relevant is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions | Baseline to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52 | 
| Median Time to Relapse (Weeks) From Week 12. | Median time to relapse (weeks) from week 12. Relapse is defined as greater than 50% loss of the maximal PASI improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative mean percentage change indicates improvement | Week 12 to week 16, 20, 24, 28, 32, 36, 40, 44, 48, and Week 52. | 
| Percent of Responders With PASI Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100 and Percent of Responders With IGA Score of 0 or 1 Who Failed to Respond to a Previous Biologic Psoriasis Therapy | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. | Week 12 | 
| Percent of Responders With PASI Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100 and Percent of Responders With IGA Score of 0 or 1 Who Failed to Respond to a Previous Biologic Psoriasis Therapy | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. | Week 52 | 
| Number of Visits With PASI 50, 75, 90, 100 Score and IGA Mod 2011 0 or 1 | PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. | Week 16, 20, 24,28,32,36,40,44,48,and Week 52 | 
| Number of Secukinumab Injections Needed to Regain PASI 75 Response From Start of Relapse After Week 12 | The number of secukinumab injections needed for participants to regain PASI 75 response from the start of relapse after week 12 | week 16, 20, 24,28,32,36,40,44,48,and Week 52 | 
| Number of Participants Developing Anti-secukinumab Antibodies | The development of anti-secunimubab anti-bodies will decrease a participant's ability to respond to secukinumab treatment. The number of participants developing anti-secukinumab anti-bodies was measured from Baseline to week 12, 24, 52 and 8 weeks after treatment at week 60 | Baseline, weeks 12, 24, 52 and 60 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Psoriasis, plaque, inflammatory skin disease, scaly patches, AIN457, secukinumab, Moderate to Severe Plaque-type Psoriasis