Study of Safety, Tolerability, and Efficacy of Secukinumab in Subjects With Moderate to Severe Nail Psoriasis

Study Overview
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Brief Summary
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This purpose of this study was to demonstrate the efficacy of secukinumab versus placebo on nail psoriasis and to assess long-term efficacy, safety and tolerability of secukinumab.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter, Study to Demonstrate the Efficacy at 16 Weeks of Secukinumab 150 and 300 mg s.c. and to Assess Safety, Tolerability and Long-term Efficacy up to 132 Weeks in Subjects With Moderate to Severe Nail Psoriasis

Conditions
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Moderate to Severe Nail Psoriasis

Intervention / Treatment
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* Biological: Secukinumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with chronic moderate to severe plaque type psoriasis for at least 6 months prior to randomization, including significant nail involvement, defined as Nail Psoriasis Severity Index (NAPSI) score ≥16 AND number of fingernails involved ≥4 AND Psoriasis Area and Severity Index (PASI) score ≥12 AND Body Surface Area (BSA) score ≥10% Candidates for systemic therapy, i.e. psoriasis inadequately controlled by topical treatment (including super potent topical corticosteroids) and/or phototherapy and/or previous systemic therapy Exclusion Criteria: Forms of psoriasis other than chronic plaque type psoriasis (e.g., pustular psoriasis, palmoplantar pustulosis, acrodermatitis of Hallopeau, erythrodermic and guttate psoriasis) Drug-induced psoriasis (e.g. new onset or current exacerbation from β-blockers, calcium channel inhibitors or lithium) Ongoing inflammatory skin diseases other than psoriasis or any other disease affecting the fingernails which may potentially confound the evaluation of study treatment effects Ongoing use of prohibited treatments (e.g. topical or systemic corticosteroids (CS), UV therapy). Washout periods do apply Prior exposure to secukinumab (AIN457) or any other biological drug directly targeting IL-17 or the IL-17 receptor Exposure to any investigational drugs within 4 weeks prior to study treatment initiation or within a period of 5 half-lives of the investigational treatment, whichever is longer History of hypersensitivity to constituents of the study treatment Other protocol-defined inclusion/exclusion criteria do 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 (AIN457) 150 mg<br>Participants assigned to secukinumab 150 mg were dosed weekly for five weeks, then once every four weeks up to and including Week 132. To maintain the blinding, patients received additional placebo injections at Weeks 17, 18 and 19. All doses of study treatment are administered by sub-cutaneous injections. | Biological: Secukinumab<br>* Study treatment was provided in pre-filled 1 mL syringes.<br>* Other names: AIN457;|
| Experimental: Secukinumab (AIN457) 300 mg<br>Participants assigned to secukinumab 300 mg were dosed weekly for five weeks, then once every four weeks up to and including Week 132. To maintain the blinding, patients received additional placebo injections at Weeks 17, 18 and 19. All doses of study treatment are administered by sub-cutaneous injections. | Biological: Secukinumab<br>* Study treatment was provided in pre-filled 1 mL syringes.<br>* Other names: AIN457;|
| Placebo Comparator: Placebo<br>Patients assigned to placebo were dosed weekly for five weeks, then at Week 8 and Week 12. At Week 16, placebo patients were randomized in a 1:1 ratio, to receive secukinumab either 150 mg or 300 mg and were dosed weekly for five weeks starting at Week 16, then once every four weeks up to and including Week 132. All doses of study treatment are administered by sub-cutaneous injections. | Biological: Placebo<br>* Placebo was provided in pre-filled 1 mL syringes.<br>* Other names: placebo secukinumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Nail Psoriasis Severity Index (NAPSI) After 16 Weeks of Treatment | The NAPSI is a tool to assess psoriatic nail involvement in patients with nail psoriasis. Each nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is given a score for nail matrix psoriasis (0-4) and nail bed psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail gets a nail matrix score and a nail bed score, the total of which is the NAPSI score for that nail ranging from 0 to 8. All 10 fingernails are assessed giving a total NAPSI score ranging from 0 to 80. A negative change from baseline indicates improvement. The adjusted mean is presented. | Baseline, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in NAPSI Score | The NAPSI is a tool to assess psoriatic nail involvement in patients with nail psoriasis. Each nail is divided with imaginary horizontal and longitudinal lines into quadrants. Each nail is given a score for nail matrix psoriasis (0-4) and nail bed psoriasis (0-4) depending on the presence of any of the features of nail psoriasis in that quadrant. Each nail gets a nail matrix score and a nail bed score, the total of which is the NAPSI score for that nail ranging from 0 to 8. All 10 fingernails are assessed giving a total NAPSI score ranging from 0 to 80. A negative change from baseline indicates improvement. | baseline, 16 weeks, 132 weeks | 
| Percentage of Participants Achieving Psoriasis Area and Severity Index 75 (PASI75) and Investigator Global Assessment (IGA Mod 2011) Response 0 or 1 Over Time up to Week 16 of the Treatment Compared to Placebo and Over Time up to Week 132 | 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). The IGA scale referred exclusively to the participant's disease at the time of the assessment. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe. To be considered IGA responder at any point in time, the patient must have an IGA score of 0 or 1 and have achieved a reduction of at least two points on the IGA scale from baseline. | 16 weeks, 132 weeks | 
| Number of Participants Who Develop Immunogenicity Against Secukinumab | The number of participants who tested positive for anti-secukinumab antibodies. It refers to the number of participants who had no positive values at baseline but developed them only after start of secukinumab treatment. None of the participants had a loss of efficacy and the test was only transiently positive. | Week 132 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate nail psoriasis, Severe nail psoriasis, psoriasis, Secukinumab