Judging the Efficacy of Secukinumab in Patients With Psoriasis Using AutoiNjector: a Clinical Trial Evaluating Treatment Results (JUNCTURE)

Study Overview
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Brief Summary
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The purpose of this study was to demonstrate efficacy of autoinjector administered 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 Autoinjectors 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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Plaque-type Psoriasis

Intervention / Treatment
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* Drug: Placebo
* Drug: Secukinumab 150mg
* Drug: Secukinumab 300mg


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.

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects who were in placebo at Week 52 cannot continue in the extension treatment period | Drug: Placebo<br>* 2 injections of placebo to secukinumab 150mg per dose<br>|
| Experimental: Secukinumab 150 mg<br>After the data base lock of week 52 data has been performed, subjects received secukinumab 150 mg treatment as open label for the remainder of the extension treatment period. | Drug: Secukinumab 150mg<br>* Secukinumab 150mg: 1 injection of 150 mg secukinumab and 1 injection of placebo to secukinumab 150mg per dose. After Week 52 database lock, study is open label so only 1 injection of secukinumab 150mg per dose were administered<br>|
| Experimental: Secukinumab 300 mg<br>After the data base lock of week 52 data has been performed, subjects received secukinumab 300 mg treatment as open label for the remainder of the extension treatment period. | Drug: Secukinumab 300mg<br>* Secukinumab 300mg (2 injections of 150mg secukinumab per dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psoriasis Area and Severity Index (PASI) 75 Response and Investigators' Global Assessment (IGA) Mod 2011 0 or 1 Response | Efficacy of secukinumab compared to placebo in subjects with moderate to severe chronic plaque-type psoriasis. PASI score was based on assessment of the head, trunk, upper limbs and lower limbs for erythema, thickening (plaque elevation, induration), and scaling (desquamation). PASI scores can range from 0, corresponding to no signs of psoriasis, up to a theoretical maximum of 72.0. PASI-based secondary variables included absolute PASI score, response rates for PASI 75. PASI 50 and PASI 90 were defined as ≥ 50% and ≥ 90% improvement from Baseline in PASI score, respectively, while PASI 100 response corresponded to complete clearing of psoriasis (PASI = 0). IGA mod 2011 was used to evaluate the overall severity of psoriatic disease, with scores ranging from 0 (clear) to 4 (severe). Treatment success was defined as achievement of IGA mod 2011 0 or 1 score. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages 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 autoinjector | Week 1 | 
| Percentage of Subjects With Possible Use-related Hazards | To assess potential use-related hazards with the secukinumab autoinjector for the subject. | Week 1 | 
| 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; 0 corresponds to worst experience while 10 corresponds to best experience. 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; 0 corresponds to worst experience while 10 corresponds to best experience. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit. | Absolute change from baseline at week 48 | 
| Percentages of Participants With PASI 50, PASI 75, PASI 90, PASI 100 and IGA Mod 2011 0 or 1 Response - Induction Period | 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 | 
| Percentages of Participants With PASI 50, PASI 75, PASI 90, PASI 100 and IGA Mod 2011 0 or 1 Response - Maintenance Period (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. 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 up to Week 52 | 
| Absolute Change From Baseline for PASI Score - Induction Period | 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 | 
| Absolute Change From Baseline for PASI Score Over Time up to Week 52 - Maintenance Period (Observed Data) | Psoriasis Area and Severity Index (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 52 | 
| Percentage of Participants in Each IGA Mod 2011 Category - Induction Period | 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 | 
| Percentages of Participants in Each IGA Mod 2011 Category Over Time up to Week 52 - Maintenance Period (Observed Data) | The Investigators' Global Assessment (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 | 
| Change From Baseline in EQ-5D up to Week 12 - Induction Period | 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 EQ-5D Over Time up to Week 52 - Maintenance Period | 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 | 
| Percentage Changes From Baseline in Dermatology Life Quality Index (DLQI) Score - Induction Period | 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. A negative median percent change from baseline indicates improvement. | Baseline, up to Week 12 | 
| Percentage Changes From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time up to Week 52 - Maintenance Period | 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. A negative median percent change from baseline indicates improvement. | Baseline, Week 52 | 
| Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 12 - Induction Period | 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 | 
| Percentages 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 | 
| Percentages of Participants With PASI 50, PASI 75, PASI 90, PASI 100 and IGA Mod 2011 0 or 1 Response After Week 52 (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. 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 160 | 
| 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 160 | 
| Percentages of Participants in Each IGA Mod 2011 Category After Week 52 (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 160 | 
| Number of Participants Developing Treatment-emergent Anti-secukinumab Antibodies | The development of anti-secunimubab anti-bodies decreases a participant's ability to respond to secukinumab treatment. The number of participants developing anti-secukinumab anti-bodies was measured from Baseline to week 216. | Baseline and at Week 12, 24, 52, 100, 148, 196, 208, and 216 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to Severe Plaque-type Psoriasis, skin disease, itching condition, Psoriasis, Skin condition, psoriasis vulgaris, relapsing/remitting psoriasis, immune-mediated systemic disease, skin lesions, red skin lesions, scaly patches, papules, plaques, itching