Clinical trial NCT02696031: Study of Efficacy and Safety of Secukinumab in Patients With Non-radiographic Axial Spondyloarthritis
Official title: A Randomized, Double-blind, Placebo-controlled Multicenter Study of Secukinumab 150 mg in Patients With Active nr- axSpA to Evaluate the Safety,Tolerability and Efficacy up to 2 Yrs, Followed by an Opt Phase of Either 150 mg or 300 mg Randomized Dose Escalation for up to Another 2 Yrs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-radiographic Spondyloarthritis
Keywords: non-radiographic spondyloarthritis
axial spondyloarthritis
Ankylosing Spondylitis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-03-02
Enrollment: 555
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a randomized, double-blind, placebo-controlled study. Approximately 555 patients were randomized to one of three treatment groups (secukinumab 150 mg Load, secukinumab 150 mg No Load or placebo in a ratio of 1:1:1):

* Group 1 (secukinumab 150 mg Load): secukinumab 150 mg (1 mL, 150 mg/mL) s.c. prefilled syringe (PFS) at baseline (BSL), Weeks 1, 2 and 3, followed by administration every four weeks starting at Week 4
* Group 2 (secukinumab 150 mg No Load): secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at BSL, placebo at Weeks 1, 2 and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4
* Group 3 (placebo): placebo (1 mL) s.c. PFS at BSL, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4 Based on the clinical judgment of disease activity by the investigator and the patient, background medications, such as NSAIDs and DMARDs, may have been modified or added to treat signs and symptoms of nr-axSpA from Week 16 on.
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to demonstrate the clinical efficacy, safety and tolerability of secukinumab compared to placebo in patients with nr-axSpA at Week 16 as well as Week 52 and long term efficacy and safety up to Week 104 (core phase) followed by an optional extension phase consisting of a 16-week randomized dose escalation treatment period and a continuous treatment period for up to Week 208

Detailed description: Patients were randomized to one of three treatment groups (1:1:1) in the core phase:

* Secukinumab 150 mg Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. pre-filled syringe (PFS) at baseline, Weeks 1, 2, and 3, followed by administration every four weeks starting at Week 4
* Secukinumab 150 mg No Load: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at baseline, placebo at Weeks 1, 2, and 3, followed by secukinumab 150 mg PFS administration every four weeks starting at Week 4
* Placebo: placebo (1 mL) s.c. PFS at baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4.

All patients received secukinumab 150 mg as open-label treatment from Week 52 up to Week 100, unless they had discontinued study treatment.

At Week 104, all patients who finished the core phase according to the protocol were asked to continue in an optional, exploratory extension phase. Patients who achieved ASAS20 response at Week 104 (Core Phase Responders) were randomized to the following treatment groups (blinded) in the extension phase:

* Core Phase Responder 150 mg: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS and placebo (1 mL) s.c. PFS every four weeks;
* Core Phase Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks.

Core Phase Non-Responders (not achieving ASAS20 at Week 104) were escalated to secukinumab 300 mg in an open-label manner.

- Core Phase Non-Responder 300 mg: 2 injections with secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS every four weeks open-label.

Starting from Week 156 onward, a patient could switch to secukinumab 300 mg open-label based on the clinical judgment of disease activity by the investigator.

Eligibility criteria: 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 Tumor Necrosis Factor (TNF) α 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

Primary outcomes:
measure: The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 Response at Week 16
timeFrame: Week 16
measure: The Number and Percentage of TNF Naive Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response
timeFrame: Week 16 and week 52
measure: The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 Response
timeFrame: Week 16
measure: The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 Response
timeFrame: Week 16
measure: The Number and Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)
timeFrame: Week 16
measure: Change in Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: Baseline and Week 16
measure: The Number and Percentage of Patients to Achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response
timeFrame: Week 16 and 52
measure: Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: Baseline and Week 16
measure: Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 16
timeFrame: Baseline and Week 16
measure: Change in Ankylosing Spondylitis Quality of Life (ASQoL) Scores at Week 52
timeFrame: Baseline and Week 52
measure: The Number and Percentage of Patients Who Achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Inactive Disease
timeFrame: Week 52
measure: Change in High Sensitivity C-reactive Protein
timeFrame: Baseline and Week 16
measure: Change in Short Form-36 Physical Component Summary (SF-36 PCS)
timeFrame: Baseline and Week 16
measure: Change in Sacroiliac Joint Edema - Week 16
timeFrame: Baseline and Week 16
measure: Change in Sacroiliac Joint Edema - Week 52
timeFrame: Baseline and Week 52
Other outcomes:
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city: Santiago de Compostela
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city: Bilbao
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city: Vigo
country: Spain
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state: Pontevedra
city: Madrid
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city: Madrid
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city: Madrid
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city: Goteborg
country: Sweden
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city: Lund
country: Sweden
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city: Uppsala
country: Sweden
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city: Basel
country: Switzerland
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city: Fribourg
country: Switzerland
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city: Ankara
country: Turkey
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country: United Kingdom
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state: Essex
city: Leytonstone
country: United Kingdom
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city: Stoke on Trent
country: United Kingdom
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state: Staffordshire
city: Worthing
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state: West Sussex
city: Bath
country: United Kingdom
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city: Doncaster
country: United Kingdom
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city: Middlesbrough
country: United Kingdom
facility: Novartis Investigative Site
city: Northampton
country: United Kingdom
facility: Novartis Investigative Site
city: Wolverhampton
country: United Kingdom
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Study officials:
References:
citation: Merola JF, McInnes IB, Deodhar AA, Dey AK, Adamstein NH, Quebe-Fehling E, Aassi M, Peine M, Mehta NN. Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications. Rheumatol Ther. 2022 Jun;9(3):935-955. doi: 10.1007/s40744-022-00434-z. Epub 2022 Mar 19.
citation: Braun J, Blanco R, Marzo-Ortega H, Gensler LS, van den Bosch F, Hall S, Kameda H, Poddubnyy D, van de Sande M, Wiksten AS, Porter BO, Shete A, Richards HB, Haemmerle S, Deodhar A. Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT. Arthritis Res Ther. 2021 Sep 4;23(1):231. doi: 10.1186/s13075-021-02613-9.
citation: Deodhar A, Blanco R, Dokoupilova E, Hall S, Kameda H, Kivitz AJ, Poddubnyy D, van de Sande M, Wiksten AS, Porter BO, Richards HB, Haemmerle S, Braun J. Improvement of Signs and Symptoms of Nonradiographic Axial Spondyloarthritis in Patients Treated With Secukinumab: Primary Results of a Randomized, Placebo-Controlled Phase III Study. Arthritis Rheumatol. 2021 Jan;73(1):110-120. doi: 10.1002/art.41477. Epub 2020 Nov 24.