An Efficacy Study of Secukinumab in Plaque Psoriasis Patients With Subclinical Psoriatic Arthritis as Measured by Musculoskeletal Ultrasound

Study Overview
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Brief Summary
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Given the role of IL-17 in the development of entheseal-driven pathology, a therapeutic strategy aimed at blocking IL-17 would be a logical option for the treatment of subclinical enthesitis in psoriasis patients. This study will be the first randomized trial of a biologic therapy versus placebo in participants with plaque psoriasis and subclinical psoriatic arthritis, using musculoskeletal ultrasound.

Detailed Description
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The primary objective of this study is to estimate the difference in effect between secukinumab 300 mg s.c. and placebo, based on change from baseline to Week 16 in the OMERACT ultrasound enthesitis score.

Official Title
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An Exploratory, Randomized, Double-blind, Parallel-group, Multicenter Study to Compare Secukinumab 300 mg With Placebo After 16 Weeks of Treatment in Adults With Moderate to Severe Plaque Psoriasis and Subclinical Enthesitis Measured by Musculoskeletal Ultrasound

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: Secukinumab 300 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of chronic plaque-type psoriasis confirmed through physical examination by a dermatologist, with at least six months of clinical history prior to the baseline visit Moderate to severe plaque psoriasis at baseline as defined as: ≥ 10 % Body Surface Area (BSA) involvement, or ≥ 3% to <10% Body Surface Area with involvement of special regions (nails, scalp, or intertriginous skin), or with a history of psoriatic arthritis in a parent Candidate for systemic therapy, defined as having psoriasis inadequately controlled by current topical and/or systemic treatment(s) (including topical corticosteroids), phototherapy, or previous systemic therapies Presence of sonographic enthesitis at screening, in at least one enthesis, defined by the presence of at least abnormal thickening and hypoechogenicity of the tendon insertion, with or without presence of Doppler signal (Grade 0-3), or by the presence of grade ≥ 2 Doppler signal, independent of gray scale abnormalities Exclusion Criteria: Diagnosis of PsA as per CASPAR confirmed by a rheumatologist (including the presence of inflammatory pain in entheses or joints), and any other known rheumatological disease affecting the assessed joints Exposure to any IL-17 or IL-23(p19) inhibitor for the treatment of psoriasis (approved or investigational) within twelve months prior to screening, or exposure to any inhibitors of TNF-ɑ and IL12/23 within six months prior to screening Previous exposure to non-biologic systemic therapy for psoriasis, including methotrexate, PDE-4 inhibitors, or systemic corticosteroids within 12 weeks or 5 half-lives (whichever is longer) prior to screening A degree of obesity that impedes proper ultrasound examination of entheses and joints Forms of diagnosed psoriasis other than chronic plaque psoriasis (e.g., erythrodermic, generalized or localized pustular psoriasis, or new onset guttate psoriasis) 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab 300mg<br>Randomized in a 2:1 ratio to secukinumab or placebo | Biological: Secukinumab 300 mg<br>* Secukinumab 300 mg administered s.c. (2 single-use prefilled syringes of 150 mg/mL), on Days 1, 8, 15, 22, 29, 57, 85.<br>* Other names: AIN457;|
| Placebo Comparator: Placebo<br>Randomized in a 2:1 ratio to secukinumab or placebo | Other: Placebo<br>* Placebo administered s.c. (2 single-use prefilled 1 mL syringes) on Days 1, 8, 15, 22, 29, 57, 85.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score | Twelve (12) entheses (bilateral AT, LE, PP, DP, PA, QT) will be scored in terms of inflammatory and morphological components according to the OMERACT enthesitis composite semi-quantitative scale (0 to 3). The lowest OMERACT score a participant can have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least one enthesis). The highest OMERACT score expected at baseline will be 72, assuming that each of the 12 entheses assessed shows a maximum of 3 points in the gray scale score, and a maximum of 3 points in the Doppler score. The largest change expected from baseline to Week 16 is -60 points (improvement). This assumes that the presence of structural changes (calcifications, enthesophytes and erosions) may add a maximum of 12 points to the score, and it may not be modifiable with study treatment during the study period. | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound enthesitis score | Sixteen (16) entheses (bilateral AT, LE, PP, DP, PA, QT, SS, TT) will be scored in terms of inflammatory components according with the GRAPPA ultrasound enthesitis score. The lowest GRAPPA score a participant may have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least 1 enthesis). The highest GRAPPA score expected at baseline is 248, assuming the maximum score that could be assigned to each enthesis. The largest change expected from baseline to Week 16 is -136 points (improvement). This value assumes that the presence of structural changes (calcifications, enthesophytes, and erosions) may add a maximum of 136 points to the score, and it may not be modifiable with study treatment during the study period. | Baseline and Week 16 | 
| Change from Baseline in the PsASon13 unilateral ultrasound composite score of synovitis | Joints examined by the PsASon13 unilateral ultrasound composite score: Small finger joints: MCP2, MCP5, H-PIP1, H-PIP2, H-PIP3; Distal interphalangeal finger joints: H-DIP3; Small joints of feet: MTP1, MTP5, F-PIP1; Distal interphalangeal joints of feet: F-DIP2, F-DIP3; Large joints: wrist and knee. Lowest score a participant may have at baseline is 0. Highest score a participant may have at baseline is 184 (5 small finger joints, each ranging from 0 to 18; 1 distal interphalangeal finger joint, each ranging from 0 to 16; 3 small joints of feet, each ranging from 0 to 12; 2 distal interphalangeal joints of feet, each ranging from 0 to 12; 1 wrist ranging from 0 to 12; and 1 knee ranging from 0 to 6). Largest change expected from baseline to Week 16 is -118 points (improvement). This assumes that the presence of structural changes (erosions and osteophytes) may add a maximum of 66 points to the score and it may not be modifiable with study treatment during the study period. | Baseline and Week 16 | 
| Number of participants who achieve complete resolution of enthesitis based on OMERACT criteria (yes, no) | Proportion of participants experiencing complete resolution of their enthesitis based on Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) score | Baseline and Week 16 | 
| Number of participants who achieve Psoriasis Area and Severity Index 90 (PASI 90) (yes, no) | Psoriasis Area Severity Index 90 Scores range from 0 to 72. A score of more than 10 generally translates to moderate-to-severe. Usually, the higher your PASI score, the lower the quality of life. A PASI 90 is at least a 90% improvement (reduction) in PASI score. | Baseline and Week 16 | 
| Number of participants who achieve Psoriasis Area and Severity Index 100 (PASI 100) (yes, no) | Psoriasis Area Severity Index 100 Scores range from 0 to 72. A score of more than 10 generally translates to moderate-to-severe. Usually, the higher your PASI score, the lower the quality of life. A PASI 100 is a complete clearing of psoriasis (PASI score = 0). | Baseline and Week 16 | 
| Number of participants who achieve Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 (yes, no) | The IGA mod 2011 scale is a visual assessment that consists of a score ranging from 0 (clear) to 4 (severe). Skin rated a 4 is bright red in color with marked plaque elevation and is dominated by thick, non-tenacious scale. For a treatment to be considered successful, the affected area must receive a score of 0 or 1 and experience a two-point improvement from Baseline. | Baseline and Week 16 | 
| Change from Baseline in Body Surface Area (BSA) | The total percentage of body surface area affected by psoriasis | Baseline and Week 16 | 
| Change from Baseline in Dermatology Life Quality Index (DLQI) score | A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life. | Baseline and Week 16 | 
| Number of participants who achieve Dermatology Life Quality Index (DLQI) score of 0 or 1 (yes, no) | A 10-item measure to assess health-related quality of life in adults with skin diseases. Scores range from 0-30 with a higher score being less quality of life. | Baseline and Week 16 | 
| Change from Baseline in HAQ-DI score | Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function). | Baseline and Week 16 | 
| Number of participants who achieve HAQ-DI change from baseline ≤ -0.35 (yes, no) | Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question scale assessing functional ability. The final HAQ-DI score ranges from 0 (no problems functioning) to 3 (not able to function). | Baseline and Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subclinical enthesitis, Psoriasis, secukinumab, subclinical psoriatic arthritis, Plaque psoriasis, AIN457