Efficacy and Safety Study of Secukinumab in Chinese Participants With Non-radiographic Axial Spondyloarthritis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy, safety and tolerability of secukinumab in Chinese patients with active nr-axSpA. Treatment difference of secukinumab 150mg vs. placebo in Chinese nr-axSpA patients in terms of ASAS 40 response rate as well as safety profile will be provided by the study.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Multicenter Study of Subcutaneous Secukinumab, to Compare Efficacy at 16 Weeks With Placebo and to Assess Safety and Tolerability up to 52 Weeks in Chinese Participants With Active Non-radiographic Axial Spondyloarthritis.

Conditions
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Non-radiographic Axial Spondyloarthritis

Intervention / Treatment
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* Drug: Secukinumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-nursing female patients at least 18 years of age Diagnosis of axial spondyloarthritis according to Ankylosing SpondyloArthritis International Society (ASAS) axial spondyloarthritis criteria Objective signs of inflammation (magnetic resonance imaging (MRI) or abnormal C-reactive protein) Active axial spondyloarthritis as assessed by total Bath Ankylosing Spondylitis Disease Activity Index >=4 cm Spinal pain as measured by Bath Ankylosing Spondylitis Disease Activity Index question #2 ≥ 4 cm (0-10 cm) at baseline Total back pain as measured by Visual Analogue scale ≥ 40 mm (0-100 mm) at baseline Patients should have been on at least 2 different non-steroidal anti-inflammatory drugs with an inadequate response Patients who have been on a TNFα inhibitor (not more than one) must have experienced an inadequate response Exclusion Criteria: Patients with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally Inability or unwillingness to undergo MRI Chest X-ray or MRI with evidence of ongoing infectious or malignant process Patients taking high potency opioid analgesics Previous exposure to secukinumab or any other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor Pregnant or nursing (lactating) women 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 Arm<br>Secukinumab 150 mg PFS s.c. | Drug: Secukinumab<br>* Secukinumab 150 mg s.c. at BSL, Weeks 1, 2, and 3, followed by administration every 4 weeks starting at Week 4.<br>* Other names: AIN457;|
| Placebo Comparator: Placebo Arm<br>Placebo 150mg PFS s.c. | Drug: Placebo<br>* Placebo 150 mg s.c.at BSL, Weeks 1, 2 and 3, followed by administration every 4 weeks starting at Week 4.<br>* Other names: AIN457 Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of TNF-α naive participants achieving an ASAS40 response (Assessment of SpondyloArthritis International Society criteria). | ASAS40 response is defined as an improvement of 40% and an absolute improvement from baseline of 2 units on a 10-point scale in at least three of the four main domains and no worsening assessed at all in the remaining domain. Main ASAS domains: Patient's global assessment of disease activity measured on a VAS scale Patient's assessment of back pain, represented by either total or nocturnal pain scores, both measured on a VAS scale Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by VAS scale Inflammation represented by mean duration and severity of morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI as measured by VAS scale | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of overall participants achieving an ASAS40 response. | ASAS40 response is defined as an improvement of 40% and an absolute improvement from baseline of 2 units on a 10-point scale in at least three of the four main domains and no worsening assessed at all in the remaining domain. | Week 16 | 
| The proportion of participants meeting the ASAS 5/6 response criteria. | ASAS 5/6 response is defined as an improvement of ≥20% in at least five of all six domains. | Week 16 | 
| The change from baseline in total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). | The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) consists of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to the 5 major symptoms of AS. | Week 16 | 
| The proportion of participants achieving BASDAI 50. | BASDAI 50 is defined as an improvement of at least 50% in the BASDAI total score compared to baseline. | Week 16 | 
| The change from baseline of high sensitivity C-Reactive Protein (hsCRP). | High sensitivity C-reactive protein is measured as a marker of inflammation from blood samples during the study | Week 16 | 
| The change from baseline in total Bath Ankylosing Spondylitis Functional Index (BASFI). | The BASFI (Bath Ankylosing Spondylitis Functional Index) is a set of 10 questions designed to determine the degree of functional limitation in those patients with AS. | Week 16 | 
| The change from baseline in sacroiliac joint (SIJ) edema on MRI. | MRI assessment of edema score of the Sacroiliac Joint. | Week 16 | 
| The proportion of participants achieving an ASAS20 response. | ASAS20 response is defined as an improvement of ≥20% and an absolute improvement from baseline of ≥1 unit on a 10-point scale in at least three of the four main domains and no worsening of ≥20% and ≥1 unit at all in the remaining domain. | Week 16 | 
| The change from baseline in Short Form-36 Physical Component Summary (SF-36 PCS). | The SF-36 (Short Form-36 Physical Component Summary) is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. | Week 16 | 
| The change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) scores. | The ASQoL (Ankylosing Spondylitis Quality of Life scores) is an instrument to measure health-related quality of life among patients with Ankylosig spondylosrthritis. | Week 16 | 
| The proportion of participants achieving ASAS partial remission. | ASAS partial remission is defined as a value not above 2 units in each of the four main ASAS domains on a 10-point scale. | Week 16 | 
| overall safety and tolerability of secukinumab. | Number of participants with adverse events (AE) serious adverse events (SAE), clinically significant changes in laboratory value and vital signs. | up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-radiographic spondyloarthritis, chronic inflammatory disease, inflammatory back pain,, secukinumab, AIN457