A Study of Secukinumab to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission

Study Overview
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Brief Summary
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This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with Non-radiographic axial spondyloarthritis, (nr-axSpA) who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response (ASDAS-CRP < 1.3). Maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120.

Detailed Description
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This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with nr-axSpA who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response Inactive Disease (ID) response (ASDAS-CRP < 1.3). The maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120. Study treatment will be as follows: Open-label Secukinumab PFS (prefilled syringe) will be labeled as AIN457 150mg/1mL Double-blind Secukinumab and Placebo PFS will be labeled as AIN457 150mg/1mL/Placebo. Study duration will be up to 128 weeks from Baseline. The treatment duration will be up to 120 weeks with last treatment administration at Week 116. In the Treatment Period 1 participant will attend a site visit approximately 1 month after Baseline and approximately every 12 weeks thereafter. In the Treatment Period 2 participant will attend site visits approximately every 4 weeks.

Official Title
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A Multicenter Study of Secukinumab, With a Randomized Double-blind, Placebo-controlled Withdrawal-retreatment Period, to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission

Conditions
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Non-radiographic Axial Spondyloarthritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-lactating female participants at least 18 years of age Clinical diagnosis of axSpA AND according to ASAS axSpA criteria: Inflammatory back pain for at least 6 months Onset before 45 years of age Sacroiliitis on MRI (magnetic resonance imaging) (as assessed by central reader) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features Objective signs of inflammation at screening, evident by either MRI with Sacroiliac Joint inflammation (as assessed by central reader) AND / OR hsCRP > ULN (as defined by the central lab) Active axSpA as assessed by total BASDAI ≥ 4 cm (0-10 cm) at baseline. Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline. Total back pain as measured by VAS (visual analog scale) ≥ 40 mm (0-100 mm) at baseline. Participants should have been on at least 2 different NSAIDs (non-steroidal anti-inflammatory drugs) at the highest recommended dose for at least 4 weeks in total prior to baseline with an inadequate response or failure to respond, or less if therapy had to be withdrawn due to intolerance, toxicity or contraindications. Exclusion Criteria: Participants with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally (radiological criterion according to the modified New York diagnostic criteria for AS) as assessed by central reader. Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine). Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor or previous treatment with immunomodulatory biologic agents including those targeting TNFα (tumor necrosis factor α) (unless participants discontinued the treatment with TNFα inhibitor due to a reason other than efficacy [primary or secondary lack of efficacy, inadequate response] and only after appropriate wash-out period prior to baseline was observed). History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes. Active ongoing inflammatory diseases other than nr-axSpA that might confound the evaluation of the benefit of secukinumab therapy, including uveitis. Active inflammatory bowel disease. 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: This phase IV, multicenter study uses a double-blind, placebo-controlled, randomized withdrawal design (Treatment Period 2) preceded by an open label lead-in period (Treatment Period 1).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Period 1<br>Open-label Secukinumab PFS (prefilled syringe) labeled as AIN457 150mg/1mL | Drug: Secukinumab<br>* Treatment Period 1: Open-label secukinumab 150 mg PFS s.c. at baseline, Weeks 1, 2, 3 and 4 followed by administration every four weeks up to Week 52.<br>|
| Experimental: Treatment Period 2<br>Double-blind Secukinumab and Placebo PFS labeled as AIN457 150mg/1mL/Placebo | Drug: Placebo<br>* Treatment Period 2: Double-blind placebo PFS s.c. every 4 weeks from Week 56 to Week 116.<br>Drug: Secukinumab<br>* Treatment Period 2: Double-blind secukinumab 150 mg PFS s.c. every 4 weeks from Week 56 to Week 116. Escape re-treatment (during Treatment Period 2): Open-label secukinumab 150 mg PFS s.c.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants remaining flare-free during Treatment Period 2 | The primary efficacy endpoint is the proportion of participants in the randomized withdrawal population remaining flare-free at Week 120. A flare is defined as ASDAS-CRP ≥ 2.1 at 2 consecutive visits, or ASDAS-CRP > 3.5 at any visit during Treatment Period 2, starting at Week 60. Parameters used for ASDAS-CRP include: Spinal pain (BASDAI question 2), Patient's global assessment of disease activity, Peripheral pain/swelling (BASDAI question 3), Duration of morning stiffness (BASDAI question 6) C-reactive protein (CRP) in mg/L | Week 120 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to flare during Treatment Period 2 | A flare is defined as ASDAS-CRP ≥ 2.1 at 2 consecutive visits, or ASDAS-CRP > 3.5 at any visit during Treatment Period 2, starting at Week 60. | From Week 56 to Week 120 | 
| Number of participants with Adverse Events | Safety and tolerability demonstrated by assessing: - Adverse events (AEs) and serious adverse events (SAEs) | From Baseline to Week 128 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nr-AxSpa, non-radiographic axial Spondyloarthritis, Secukinumab, remission, withdrawal, inflammatory back pain, sacroiliitis, AIN457