Efficacy and Safety of Intravenous and Subcutaneous Secukinumab in Moderate to Severe Chronic Plaque-type Psoriasis

Study Overview
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Brief Summary
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The study will assess the safety and efficacy of intravenous (10mg/kg) and subcutaneous (300mg) secukinumab in moderate to severe chronic plaque-type psoriasis who are partial responders to secukinumab.

Official Title
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A Randomized, Double-blind, Double Dummy, Multicenter Study to Assess the Safety, Tolerability and Long-term Efficacy of Intravenous (10mg/kg) and Subcutaneous (300mg) Secukinumab in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Who Are Partial Responders to Secukinumab

Conditions
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Plaque-type Psoriasis

Intervention / Treatment
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* Drug: secukinumab 150mg
* Drug: secukinumab 10mg/kg i.v. regimen


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, Subject must be able to understand and communicate with the investigator and comply with the requirements of the study. Subjects must have participated in the study CAIN457A2304 and have achieved a partial response after twelve weeks of treatment with no major protocol deviations. A partial response is defined as having achieved ≥ PASI 50 but < 75 response. Exclusion criteria Pregnant women or lactating women Forms of psoriasis other than chronic plaque -type Ongoing use of prohibited psoriasis treatments Ongoing use of other non-psoriasis prohibited treatments Previous exposure to any biologic drug directly targeting IL-17 or the IL-17 receptor, except secukinumab in study CAIN457A2304 Active ongoing inflammation diseases other than psoriasis that might confound the evaluation of the benefits of secukinumab therapy UV therapy or excessive exposure to sunlight

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 subcutaneous (s.c.)<br>During the intravenous (I.V.) period, participants received two 150 mg s.c. injections of AIN457 at randomization and week 4, and AIN457 placebo I.V. at randomization, week 2 and week 4. During the maintenance period, participants received 300 mg s.c. of open-label AIN457. | Drug: secukinumab 150mg<br>* secukinumab 150mg (2 injections per dose)<br>|
| Experimental: AIN457 I.V.<br>During the I.V. period, participants received AIN457 10mg/kg I.V. at randomization, week 2 and week 4, and AIN457 placebo s.c. at randomization and week 4. During the maintenance period, participants received 300 mg s.c. of open-label AIN457. | Drug: secukinumab 10mg/kg i.v. regimen<br>* secukinumab 10mg/kg i.v. regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants (Who Achieved a Partial Response Defined as ≥ 50% But < 75% Improvement in Psoriasis Area and Severity Index (PASI) After 12 Weeks of Treatment in Study AIN457A2304) With 75% Improvement From Baseline in PASI | 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). | Week 8 | 
| Percentage of Participants (Who Achieved a Partial Response Defined as ≥ 50% But < 75% Improvement in PASI After 12 Weeks of Treatment in Study AIN457A2304) With Investigator's Global Assessment Model 2011 (IGA Mod 2011) 0 or 1 Response | 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. Treatment success was defined as achievement of IGA mod 2001 score of 0 or 1. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving PASI 50/75/90/100 Response or IGA 0 or 1 Response | 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. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40 | 
| Mean Percent Change From Baseline in PASI Scores | 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. | Baseline, weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40 | 
| Percentage of Participants in Each IGA Mod 2011 Score Category | 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. | Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40 | 
| Percentage of Participants Who Achieved Dermatology Life Quality Index (DLQI) of 0 or 1 | The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral warts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A DLQI of 0 or 1 indicates no impairment or little impairment, respectively. A negative mean percentage change from baseline indicates improvement. | Baseline, Week 8, Week 16, Week 24, Week 32,up to Week 40 | 
| Mean Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Scores | The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement. | Baseline, weeks 8, 16, 24, 32 and 40 | 
| Mean Percent Change From Baseline in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment (From 0 to 100) | The EQ-5D is an instrument used to assess a participant's health status. The instrument includes a descriptive profile and a visual analog scale (VAS). The descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 response levels: no problems, some problems and severe problems. The VAS is a vertical scale that assesses the health status from 0 (worst possible health state) to 100 (best possible health state). This outcome measures the percent change in VAS score. Positive mean percent changes indicate improvement. | Baseline, weeks 8, 16, 24, 32 and 40 | 
| Number of Participants Who Developed Anti-secukinumab Antibodies | The development of anti-secunimubab anti-bodies would decrease a participant's ability to respond to secukinumab treatment. | Baseline, weeks 12, 24 and 40 | 
| Relationship Between Response to AIN457 and Failed Response to Previous Biologic Psoriasis Therapy | This outcome measure was not analyzed due to the small sample size of the study (43 participants). | End of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, plaque, inflammatory skin disease, scaly patches, AIN457, secukinumab, Moderate to severe