SKIPPAIN - Speed of Onset of SecuKinumab-Induced Relief From Pain in Patients With AxIal SpoNdyloarthritis

Study Overview
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Brief Summary
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The purpose of the study was to evaluate the efficacy and safety of secukinumab 150 mg compared to placebo in the early management (Baseline to Week 8) of spinal pain, disease activity, fatigue, and predictability of disease flares in patients with axial spondyloarthritis (axSpA) who had an inadequate response to prior non-steroidal anti-inflammatory drugs (NSAIDs). This study also explored the efficacy and safety of secukinumab 300 mg compared to secukinumab 150 mg from Week 8 to Week 24 in order to assess the potential additional benefits of dose escalation in patients with axSpA.

Detailed Description
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The study consisted of 2 treatment periods: a double-blind, placebo-controlled period from Baseline to Week 8 (Treatment Period 1) and a double-blind secukinumab treatment period from Week 8 to Week 24 (Treatment Period 2). At Baseline (Treatment Period 1), patients were randomized in a 3:1 ratio to either secukinumab 150 mg (Group A) or placebo (Group B). At Week 8 (Treatment Period 2), patients were re-randomized and re-assigned respectively to 1 of 5 treatment arms to receive either secukinumab 150 mg or secukinumab 300 mg. Patients assigned to secukinumab 150 mg (Group A) at Baseline who were responders (i.e. spinal pain score < 4) at Week 8 continued on the same dose until Week 24 under 1 treatment arm (Arm A1). Patients assigned to secukinumab 150 mg at Baseline who were non-responders at Week 8 were re-randomized to 1 of 2 treatment arms: secukinumab 150 mg (Arm A2) or secukinumab 300 mg (Arm A3) from Week 8 to Week 24. Similarly, patients assigned to placebo (Group B) at Baseline were re-randomized to 1 of 2 treatment arms: secukinumab 150 mg (Arm B1) or secukinumab 300 mg (Arm B2) from Week 8 until Week 24.

Official Title
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A 24-week, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Secukinumab in Controlling Spinal Pain in Patients With Axial Spondyloarthritis

Conditions
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Spondyloarthritis

Intervention / Treatment
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* Biological: AIN457
* Drug: AIN457 Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of axial spondylarthritis (axSpA, either ankylosing spondylitis or non radiographic axial spondylarthritis) according to ASAS axSpA classification criteria patients with back pain for at least 3 months and age of onset less than 45 years Active axSpA as assessed by total BASDAI score of at least 4 at Baseline. Spinal pain numeric rating scale score of more than 4 at Baseline. inadequate response to or failure to respond to at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks in total prior to randomization Key Exclusion Criteria: Chest X-ray or MRI with evidence of ongoing infectious or malignant process Patients previously treated with any biological immunomodulating agents, except those targeting tumor necrosis factor alpha. Patients who have been exposed to more than one anti-tumor necrosis factor alpha agent. Active ongoing inflammatory diseases other than axial spondyloarthritis Other ongoing mechanical diseases affecting the spine.

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 150 mg (Group A)<br>Treatment Period 1: Secukinumab 150 mg (1 x 1.0 mL) s.c. administered at Baseline, Week 1, 2, 3 and 4 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;|
| Placebo Comparator: Placebo (Group B)<br>Treatment Period 1: Placebo (1 x 1.0 mL) s.c. administered at Baseline and Week 1, 2, 3 and 4 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;Drug: AIN457 Placebo<br>* Placebo matching AIN457<br>* Other names: Placebo;|
| Active Comparator: Arm A1<br>Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;Drug: AIN457 Placebo<br>* Placebo matching AIN457<br>* Other names: Placebo;|
| Active Comparator: Arm A2<br>Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;Drug: AIN457 Placebo<br>* Placebo matching AIN457<br>* Other names: Placebo;|
| Active Comparator: Arm A3<br>Treatment Period 2: Secukinumab 300 mg (2 x 1.0 mL) administered at Week 8, 12, 16, and 20 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;|
| Active Comparator: Arm B1<br>Treatment Period 2: Secukinumab 150 mg (1 x 1.0 mL) plus placebo (1 x 1.0 mL) administered at Week 8, 12, 16 and 20 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;Drug: AIN457 Placebo<br>* Placebo matching AIN457<br>* Other names: Placebo;|
| Active Comparator: Arm B2<br>Treatment Period 2: Secukinumab 300 mg (2 x 1.0 mL) administered at Week 8, 12, 16, and 20 | Biological: AIN457<br>* anti IL-17a monoclonal antibody<br>* Other names: secukinumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Spinal Pain Numerical Rating Scale (NRS) Score Below 4 at Week 8 (Treatment Period 1) | The spinal pain numerical rating scale (NRS) is an 11-point scale to assess pain intensity in patients who are able to self-report. It is an 11-point scale from 0-10: 1) 0 = no pain. 2) 10 = the most intense pain imaginable. To calculate the average spinal pain, the patient was asked to answer 2 questions to get 2 pain ratings, the total spinal pain corresponding to the intensity of spinal pain experienced on an average over 24 hours during the previous week and the nocturnal back pain corresponding to the intensity of spinal pain experienced on an average over the night during the previous week. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Bath Ankylosing Spondylitis Disease Activity Index Score Below 4 at Week 8 (Treatment Period 1) | The Bath ankylosing spondylitis disease activity index (BASDAI) consists of a 0 through 10 scale, which is used to answer 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis. To give each symptom equal weighting, the mean (average) of the 2 scores relating to morning stiffness (questions 5 and 6) is taken. The mean of questions 5 and 6 is added to the scores from questions 1-4. The resulting 0 to 50 score is divided by 5 to give a final 0 - 10 BASDAI score. | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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axial spondyloarthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, inflammatory back pain, spinal pain, secukinumab, AIN457