16-week Efficacy and 3-year Safety, Tolerability and Efficacy of Secukinumab in Active Ankylosing Spondylitis Patients

Study Overview
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Brief Summary
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The purpose of this study was to generate 16-week efficacy data, as well as up to 3-year efficacy, safety and tolerability data in subjects with active AS despite current or previous NSAID, DMARD and/or anti-TNF therapy.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase III Study of Secukinumab to Demonstrate the Efficacy at 16 Weeks and to Assess the Long-term Safety, Tolerability and Efficacy up to 3 Years in Subjects With Active Ankylosing Spondylitis

Conditions
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Spondylitis, Ankylosing

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: moderate to severe AS, prior radiographic evidence according to the Modified NY Criteria (1984), inadequate response to NSAIDs. -- Exclusion criteria: pregnancy or lactation, on-going infectious or malignant process on a chest X-ray or MRI, previous exposure to IL-17 or IL-17R targeting therapies, previous exposure to any biological immunomodulating agent excluding TNF antagonists, previous cell depleting therapy.

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 10 mg/kg i.v. / 300 mg s.c.<br>Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study. | Drug: Secukinumab<br>* AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17).<br>* Other names: AIN457;|
| Experimental: Secukinumab 10 mg/kg i.v. / 150 mg s.c.<br>Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection every four weeks until the end of the study. | Drug: Secukinumab<br>* AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17).<br>* Other names: AIN457;|
| Placebo Comparator: Placebo i.v. and s.c.<br>Three i.v. infusions: at Baseline and weeks 2 and 4, followed by one s.c. injection at weeks 8 and 12. At week 16, patients were re-randomised to one of the active treatment arms, to receive secukinumab s.c. Q4W until the end of the study. | Drug: Placebo secukinumab<br>* Placebo to AIN457 (Secukinumab)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 20% Improvement in the Assessment of Spondyloarthritis International Society Criteria Scale / ASAS 20 Response | ASAS 20 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 20% improvement in score in at least 3 of a conventional set of 4 clinical domains relevant to AS and no worsening in the fourth domain. In this study, ASAS 20 was used to assess the efficacy of at least one dose of secukinumab versus placebo. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASAS 40 Response | ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 40% improvement in score in at least 3 of a conventional set of 4 clinical domains relevant to AS and no worsening in the fourth domain. In this study, ASAS 40 was used to assess the efficacy of at least one dose of secukinumab versus placebo. | 16 weeks | 
| Serum hsCRP | Blood levels of C-reactive protein (CRP), an acute phase reactant, are indicative of inflammation and of its severity, and can be used to monitor treatment response. A high sensitivity CRP (hsCRP) test was implemented in this study, to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over the time. | Baseline and 16 weeks | 
| ASAS 5/6 Response | ASAS 5/6 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevant to AS and no worsening in the remaining domain. In this study, ASAS 5/6 was used to assess the efficacy of at least one dose of secukinumab versus placebo. | 16 weeks | 
| Bath Ankylosing Spondylitis Disease Activity Index / BASDAI | BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating no problem and 10 indicating worst problem), to characterise six clinical domains pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, the BASDAI index was used to assess the efficacy of at least one dose of secukinumab versus placebo. | Baseline and 16 weeks | 
| Number of Participants With Successful Self-administration (to Measure Usability of Pre-filled Syringe) | Successful self-administration is defined as success in steps P8 (Removed Needle Cap from Safety Syringe), P10 (Pinched the Skin at Injection Site), P11 (Inserted the Needle into Skin), P12 (Held onto the Finger Flange), P13 (Fully Depressed Plunger until End Point), and P14 (Held Plunger Down and Syringe in Place) of the Instructions for Use, as observed by the site staff at applicable visits. | Week 8 and Week 12 | 
| Pre-filled Syringe Possible Hazard | The number and percentage of subjects who experience any of the defined possible hazards are summarized, as defined in the Possible Hazard assessment check list and as observed by the site staff at applicable visits. | Week 8 and Week 12 | 
| Prefilled Syringe Patient Satisfaction Assessment | The self-injection assessment questionnaire (SIAQ) measures overall patient experience with subcutaneous self-injection at applicable visits. Domain scores ranging from 0 (worst experience) to 10 (best experience) are presented: Feeling about injections, Self-confidence, Satisfaction with self-injection. | Baseline, weeks 8, 12 and 16 | 
| ASAS Partial Remission | ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale of 10. In this study, ASAS partial remission was used to assess the efficacy of at least one dose of secukinumab versus placebo. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIN457, ankylosing spondylitis, chronic inflammatory disease, inflammatory back pain, secukinumab, self-injection