Study of Efficacy and Safety of Secukinumab 2 mL Auto-injector (300 mg) in Subjects With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The primary purpose of this study is to assess efficacy, safety and tolerability of a 2 mL pre-filled auto-injector (AI) of 300 mg secukinumab in patients with moderate to severe plaque psoriasis

Detailed Description
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This is a 52-weeks multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in approximately 120 subjects with moderate to severe plaque-type psoriasis

Official Title
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Multicenter, rAndomized, Double-blind, Placebo-conTrolled, 52-week stUdy to demonstRatE the Efficacy, Safety and Tolerability of Secukinumab Injections With 2 mL Auto-injectors (300 mg) in Adult Subjects With Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Placebo 2 mL auto-injector
* Drug: Placebo 1 mL prefilled syringe
* Drug: Secukinumab 2 mL auto-injector
* Drug: Secukinumab 1 mL prefilled syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects eligible for inclusion in this study must have fulfilled all of the following criteria: Men or Women of at least 18 years of age at time of Screening Subjects able to understand and communicate with the investigator and comply with the requirements of the study and must have given a written, signed and dated informed consent before any study related activity was performed. Where relevant, a legal representative signed the informed study consent according to local laws and regulations. Chronic plaque-type psoriasis present for at least 6 months and diagnosed before Randomization. Moderate to severe psoriasis as defined at Randomization by: PASI score of 12 or greater, and IGA mod 2011 score of 3 or greater (based on a scale of 0 - 4), and Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater. Candidate for systemic therapy. This is defined as a subject having moderate to severe chronic plaque-type psoriasis that is inadequately controlled by Topical treatment and/or Phototherapy and/or Previous systemic therapy Exclusion Criteria: Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at Screening or Randomization. Ongoing use of prohibited treatments. Washout periods detailed in the protocol had to be adhered to. Subjects not willing to limit UV light exposure (e.g., sunbathing and/or the use of tanning devices) during the course of the study were considered not eligible for this study since UV light exposure was prohibited. Note: administration of live vaccines 6 weeks prior to Randomization or during the study period was also prohibited. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17 or the IL-17 receptor. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect had returned to baseline, whichever is longer; or longer if required by local regulations. Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there was evidence of local recurrence or metastases (except for Bowen's disease, or basal cell carcinoma or actinic keratoses that had been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed). History of hypersensitivity to any of study drug constituent

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
Interventional Model Description: A Phase IIIb 52-week multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in approximately 120 subjects with moderate to severe plaque-type psoriasis
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo 2 mL auto-injector<br>Placebo to secukinumab s.c., provided in 2 mL auto-injector form | Drug: Placebo 2 mL auto-injector<br>* All Placebo patients until week 8 (included): 2 mL auto-injector Placebo + 2x 1 mL prefilled syringe Placebo s.c. at randomization, weeks 1, 2, 3, 4 and 8. PASI 90 responders at week 12: 2 mL auto-injector placebo + 2x 1 mL prefilled syringe Placebo s.c. at weeks 12, 13, 14, 15, 16 and every 4 weeks thereafter until week 48. PASI 90 non-responders at week 12: 2 mL secukinumab 300 mg auto-injector + 2x 1 mL prefilled syringe Placebo s.c. at weeks 12, 13, 14, 15, 16 and 4-weekly thereafter until week 48<br>* Other names: Placebo;|
| Placebo Comparator: Placebo 1 mL prefilled syringe<br>Placebo to secukinumab s.c., provided in 2 * 1 ml prefilled syringe form | Drug: Placebo 1 mL prefilled syringe<br>* All Placebo patients until week 8 (included): 2 mL auto-injector Placebo + 2x 1 mL prefilled syringe Placebo s.c. at randomization, weeks 1, 2, 3, 4 and 8. PASI 90 responders at week 12: 2 mL auto-injector Placebo + 2x 1 mL prefilled syringe Placebo s.c. at weeks 12, 13, 14, 15, 16 and every 4 weeks thereafter until week 48. PASI 90 non-responders at week 12: 2x 1 mL secukinumab 150 mg prefilled syringe + 2 mL auto-injector Placebo s.c. at weeks 12, 13, 14, 15, 16 and 4-weekly thereafter until week 48<br>* Other names: Placebo;|
| Experimental: Secukinumab 2 mL auto-injector<br>Secukinumab 300 mg provided in 2 mL auto-injector form | Drug: Secukinumab 2 mL auto-injector<br>* 2 mL secukinumab 300 mg auto-injector + 2x 1 mL prefilled syringe Placebo s.c. at randomization, weeks 1, 2, 3, 4, 8, 12, 13, 14, 15 , 16 and 4-weekly thereafter until week 48<br>|
| Active Comparator: Secukinumab 1 mL prefilled syringe<br>Secukinumab 300 mg provided as 2x 1 mL prefilled syringe of 150 mg/mL | Drug: Secukinumab 1 mL prefilled syringe<br>* 2 x 1 mL secukinumab 150 mg prefilled syringe + 2 mL auto-injector Placebo s.c. at randomization, weeks 1, 2, 3, 4, 8, 12, 13, 14, 15, 16 and 4-weekly thereafter until week 48<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI 75 Response After 12 Weeks of Treatment | Percentage of participants who achieve ≥ 75% reduction in PASI compared to baseline. A PASI (Psoriasis Area and Severity Index) score is a tool used to measure the severity and extent of psoriasis. The score ranges from 0 (no signs of psoriasis) to a theoretic maximum of 72. The intensity of redness, thickness and scaling of the psoriasis is assessed as none (0), mild (1), moderate (2), severe (3) or very severe (4). | 12 weeks | 
| IGA Mod 2011 0 or 1 Response After 12 Weeks of Treatment | Percentage of participants who achieve IGA mod 2011 0 or 1, and improved by at least 2 points on the IGA scale compared to baseline. This scale ranges from 0 (clear, no signs of psoriasis) to 4 (severe). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI 90 Response | Percentage of participants who achieve ≥ 90% reduction in PASI compared to baseline | 12 weeks | 
| PASI 50, 75, 90 and 100 and IGA Mod 2011 0 or 1 Response | Percentage of participants who achieve ≥ 50%, 75%, 90% and 100% reduction in PASI and achieve IGA mod 2011 0 or 1, and improved by at least 2 points on the IGA scale compared to baseline at each visit up to 52 weeks | 52 weeks | 
| Successful Self-injection | Subject usability (ability to follow instructions for use and potential use-related hazards) and satisfaction with the new secukinumab 2 mL AI utilizing a self-administered Self-Injection Assessment Questionnaire (SIAQ) and investigator/site staff observation of secukinumab 300 mg 2 mL AI administration. The Satisfaction with Self-Injection (SA) domain score ranges from 0 (worst experience) to 10 (best experience). | From randomization until Week 28 | 
| Dermatology Life Quality Index, (DLQI) 0 or 1 Score (Total Score) | DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best. | Change from Baseline up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plaque psoriasis, auto-injector, 2 mL injection, secukinumab