First Study of Secukinumab in Pre-filled Syringes in Subjects With Chronic Plaque-type Psoriasis: Response at 12 Weeks

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate efficacy of secukinumab at Week 12 based on PASI and IGA response rates versus placebo in subjects with moderate to severe chronic plaque-type psoriasis.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Multicenter Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate Efficacy After Twelve Weeks of Treatment, and to Assess the Safety, Tolerability, Usability and Long-term Efficacy in Subjects With Chronic Plaque-type Psoriasis

Conditions
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Moderate to Severe Plaque-type Psoriasis

Intervention / Treatment
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* Drug: secukinumab 150 mg
* Drug: secukinumab 300 mg
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Moderate and severe plaque-type psoriasis diagnosed for at least 6 months. Severity of psoriasis disease meeting all of the following three criteria: Psoriasis Area and Severity Index (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
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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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: secukinumab 150 mg<br>Drug | Drug: secukinumab 150 mg<br>* After the data base lock of week 52 data has been performed, subjects will receive secukinumab 150 mg treatment as open label for the remainder of the extension treatment period<br>|
| Experimental: secukinumab 300 mg<br>Drug | Drug: secukinumab 300 mg<br>* After the data base lock of week 52 data has been performed, subjects will receive secukinumab 300 mg treatment as open label for the remainder of the extension treatment period<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* Subjects who were on placebo at Week 52 cannot continue in the extension treatment period<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 at Week 12 Measure: PASI 75 (Psoriasis Area and Severity Index) Response. | 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 weeks | 
| Efficacy of Secukinumab Compared to Placebo in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure:IGA (Investigator's Global Assessment) With a 0 or 1 Response at Week 12 | The IGA 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 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 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 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Self Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 12 | The three domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit. | Week 12 | 
| Absolute Change From Baseline in Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 48 | The three domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit. | Baseline, week 48 | 
| Number of Subjects With Potential Use Related Hazards at Week 1 | To assess potential use-related hazards with the secukinumab PFS for the subject | Week 1 | 
| Percentage of Subjects With Successful Self Administration of Study Drug at Week 1 | To assess the subject's ability to follow instructions for use with the secukinumab PFS | Week 1 | 
| Percent of Responders With Psoriasis Area and Severity Index (PASI) Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100, (Induction) With Non-responder Imputation | 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. | Week 12 | 
| Percent of Responders With Psoriasis Area and Severity Index (PASI) Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100, (Maintenance; Observed Data) | 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. | Week 52 | 
| Percent of Responders With Investigator's Global Assessment (IGA) Mod 2011 Score of 0 or 1, (Maintenance; Observed Data) | 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 | 
| Absolute Change From Baseline for PASI Score at Week 12, (Induction) | 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) | Week 12 | 
| Absolute Change From Baseline for PASI Score Over Time up to Week 52, (Maintenance; Observed Data) | 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) | Week 52 | 
| Number of Participants in Each Investigator's Global Assessment (IGA) Mod 2011 Category at Week 12, (Induction) | The IGA mod 2011 category 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 | 
| Percentage of Participants in Each Investigator's Global Assessment (IGA) Mod 2011 Category Over Time up to Week 52, (Maintenance; Observed Data) | The IGA mod 2011 category 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 | 
| Change From Baseline in EQ-5D at Week 12 (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) | Week 12 | 
| Change From Baseline in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Over Time 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) | Week 52 | 
| Median Percentage Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score, (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. This result was reflected in the percentage change from baseline at Week 12, higher reductions (improvements) in DLQI scores (median treatment difference). | Baseline and week 12 | 
| Median Percentage Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time 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. This result was reflected in the percentage change from baseline at Week 12, higher reductions (improvements) in DLQI scores (median treatment difference). | Baseline and week 52 | 
| Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 12, (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 | Week 12 | 
| Percentage of Participants Achieving a DLQI Score of 0 or 1 Over Time 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 | Week 52 | 
| Number of Responders With PASI Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100 After Week 52 | 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. | Week 172 | 
| Absolute Change From Baseline for PASI Score After Week 52, (Observed Data) | 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) | Week 172 | 
| Number of Participants in Each IGA Mod 2011 Category After Week 52 (Observed Data) | 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 | Week 172 | 
| Number of Participants Developing Treatment Emergent Anti-secukinumab Antibodies, Immunogenicity | 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 8 weeks after last treatment | Baseline and at Week 12, 24, 52, 100, 148, and 196, 204 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis