Study of Efficacy and Safety of Secukinumab in Psoriatic Arthritis and Axial Spondyloarthritis Patients With Active Enthesitis Including One Achilles Tendon Site

Study Overview
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Brief Summary
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The purpose of this study was to demonstrate efficacy, including effects on inflammation by magnetic resonance imaging (MRI) assessments, of secukinumab on Achilles tendon enthesitis for up to 1 year with a primary focus at Week 24, in patients with active Psoriatic Arthritis and axial Spondyloarthritis despite current or previous non-steroidal anti-inflammatory drugs (NSAID) and/or disease modifying anti-rheumatic drug (DMARD) and/or anti-TNFα therapy.

Detailed Description
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Primary endpoint was at week 24 but there was no interim Clinical Study Report. While Protocol states at chapter 9.7 that a week 24 analysis may be provided (not mandatory as per protocol), all data has been analyzed at week 52. Some of the secondary endpoints include the whole study period up to week 52 (to address questions on switching placebo to active drug)

Official Title
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A Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab to Demonstrate Efficacy in the Treatment of Enthesitis at the Achilles Tendon up to 1 Year in Adult Patients With Active Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA) (ACHILLES)

Conditions
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Psoriatic Arthritis, Axial Spondyloarthritis, Enthesitis

Intervention / Treatment
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* Biological: Secukinumab
* Drug: Secukinumab Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: - Patients with Psoriatic arthritis: Diagnosis of Psoriatic arthritis as per the Classification criteria for Psoriatic Arthritis (CASPAR criteria) with symptoms for at least 6 months and active Psoriatic arthritis as assessed by ≥ 1 tender joints out of 78 and ≥ 1 swollen joints out of 76 at Baseline (dactylitis of a digit counts as one joint each). - Patients with Axial Spondyloarthritis: Diagnosis of Axial Spondyloarthritis as per the classification of the Assessment of Spondyloarthritis International Society axial Spondyloarthritis (ASAS) criteria and objective signs of inflammation at Screening (magnetic resonance imaging (MRI) or definite radiographic sacroilitis and/or abnormal C-Reactive Protein) and active disease assessed by total Bath ankylosing spondylitis disease activity index (BASDAI) ≥ 4 (0-10) at Baseline. Diagnosis of Achilles tendon enthesitis according to swelling and tenderness at the insertional site of the Achilles tendon into the calcaneus. Onset of heel pain ≥ 1 month at Baseline. Heel enthesitis that is magnetic resonance imaging (MRI)-positive according to the investigator's judgement. Patients who have been exposed to up to two TNFα inhibitors. Key Exclusion Criteria: Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process. Previous exposure to secukinumab or other biologic drug directly targeting Interleukin (IL)-17 or Interleukin (IL)-17 receptor. Ongoing use of psoriasis treatments / medications (e.g. topical corticosteroids, ultraviolet (UV) therapy) at randomization. Patients who have previously been exposed to more than two Tumor necrosis factor (TNF) inhibitors (investigational or approved). Patients who have ever received biologic immunomodulating agents (investigational or approved), except those targeting Tumor necrosis factor (TNF) inhibitors. Pregnant or nursing (lactating) women. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.

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: Randomized Double-blind
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AIN457/Secukinumab<br>Secukinumab 150 mg s.c. or Secukinumab 300 mg s.c., respective dose was assigned according to underlying condition, in case of PsA according to severity of concomitant Psoriasis or pre-exposure to anti-TNFα | Biological: Secukinumab<br>* Induction: Week 0,1,2,3 150 mg or 300 mg Secukinumab s.c. Maintenance: 150 mg or 300 mg Secukinumab s.c. every 4 weeks starting at Week 4<br>* Other names: AIN457A;|
| Placebo Comparator: AIN457/Secukinumab Placebo<br>Secukinumab Placebo s.c. | Drug: Secukinumab Placebo<br>* Induction: Week 0,1,2,3 Secukinumab Placebo s.c. Maintenance: Secukinumab Placebo s.c. every 4 weeks starting at Week 4 until Week 24 followed by 150 or 300 mg Secukinumab s.c. every 4 weeks<br>* Other names: AIN457/Secukinumab Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of Patients With Resolution of Achilles Tendon Enthesitis | Number (%) of patients with resolution of Achilles tendon enthesitis (affected foot) as assessed by respective subcomponent of Leeds enthesitis index (LEI) at Week 24. The primary analysis was performed via a logistic regression model with the factors treatment, country, and stratification factor diagnosis (PsA or axSpA); patients with a missing assessment were considered as responders if they had already met the response criterion at the time of last assessment. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change of Heel Pain | Mean change of heel pain from baseline to Week 24 measured by Numeric Rating Scale (NRS) ranging from 0 to 10, with 0 representing no pain and 10 representing worst pain (e.g. pain as bad as you can imagine or worst pain imaginable). | Week 24 | 
| Number (%) of Patients With Improvement of Bone Marrow Edema | Number (%) of patients with an improvement of bone marrow edema from baseline to Week 24 as assessed by the respective subcomponent of the Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) in the affected foot. | Week 24 | 
| Number (%) of Patients With Resolution of Enthesitis as Assessed by LEI | Number (%) of patients with resolution of enthesitis as assessed by the Leeds enthesitis index (LEI) at Week 24. | Week 24 | 
| Mean Change of Physician's Global Assessment of Disease Activity | Mean change of physician's global assessment (PhGA) of disease activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe. | Week 24 | 
| Mean Change of Patient's Global Assessment of Disease Activity | Mean change of patient's global assessment (PGA) of disease activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe. | Week 24 | 
| Mean Change of Physician's Assessment of Heel Enthesopathy Activity | Mean change of physician's assessment of heel enthesopathy activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe. | Week 24 | 
| Mean Change of Patient's Assessment of Heel Enthesopathy Activity | Mean change of patient's assessment of heel enthesopathy activity from baseline to Week 24 measured by Visual Analog Scale (VAS) ranging from 0 to 100, with 0 representing not severe and 100 representing very severe. | Week 24 | 
| Mean Change in Short Form-36 (SF-36) v2 | Mean change in Short Form-36 (SF-36) v2 as an indicator of overall health status The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 Lower scores = more disability, higher scores = less disability | Week 24 | 
| Percentage of Patients With Resolution of Achilles Tendon Enthesitis After Switching From Placebo to Secukinumab | Percentage of patients with resolution of Achilles tendon enthesitis (affected foot) after switching from placebo to secukinumab at Week 24 | Weeks 24 and 52 | 
| Mean Change of Heel Pain After Switching From Placebo to Secukinumab | Mean change of heel pain after switching from placebo to secukinumab from Week 24 to week 52 measured by Numeric Rating Scale (NRS) ranging from 0 to 10, with 0 representing no pain and 10 representing worst pain (e.g. pain as bad as you can imagine or worst pain imaginable). | Change from week 24 to week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Active psoriatic arthritis, Axial spondyloarthritides, Subcutaneous, Secukinumab in prefilled syringe, Enthesitis, Achilles tendon, AxSpA, PsA