The purpose of this study is to evaluate the safety and efficacy of secukinumab 300mg in Chinese adults participants with active ankylosing spondylitis (AS) who have had an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) or intolerance to or a contraindication for NSAIDs, and who are naïve to biologic disease-modifying anti-rheumatic drugs (bDMARD).
Participant with a clinical diagnosis of ankylosing spondylitis (AS) and meeting the modified New York criteria for AS.
Participant must have baseline disease activity as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >= 4 and a Patient's Assessment of ●Total Back Pain score >= 4 based on a 0 - 10 numeric rating scale (NRS) at the Screening and Baseline visits.
Participant has had an inadequate response to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or participant has an intolerance to or contraindication for NSAIDs as defined by the Investigator.
If entering the study on concomitant methotrexate (MTX), leflunomide, sulfasalazine (SSZ), and/or hydroxychloroquine, participant must be on a stable dose of MTX (<= 25 mg/week) and/or SSZ (<= 3 g/day) and/or hydroxychloroquine (<= 400 mg/day) or leflunomide (<= 20 mg/day) for at least 28 days prior to the Baseline visit. A combination of up to two background conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is allowed except the combination of MTX and leflunomide.
Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
Prior exposure to any biologic therapy with a potential therapeutic impact on spondyloarthritis (SpA).
Intra-articular joint injections, spinal/paraspinal injection(s), or parenteral administration of corticosteroids within 28 days prior to the Baseline visit. Inhaled or topical corticosteroids are allowed.
Participant on any other DMARDs (other than those allowed), thalidomide or apremilast within 28 days or five half-lives (whichever is longer) of the drug prior to the Baseline visit.
Parallel
Secukinumab 300mg s.c.
DrugInduction: 5 x 150 mg secukinumab s.c. weekly. Maintenance: 300 mg secukinumab s.c. every 4 weeks
Secukinumab 150mg s.c.
DrugInduction: 5 x 150 mg secukinumab s.c. weekly. Maintenance: 150 mg secukinumab s.c. every 4 weeks
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24
ASAS 40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units) in the potential remaining domain: Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity); Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 48
ASDAS is a composite index to assess disease activity in Ankylosing Spondylitis. ASDAS combines the following 5 disease activity variables using a weighted formula: Patient's assessment of total back pain (BASDAI Question 2; NRS score 0 \[none\] - 10 \[very severe\]) Patient global assessment of disease activity (NRS score 0 \[no activity\] - 10 \[severe activity\]) Peripheral pain/swelling (BASDAI Question 3; NRS score 0 \[none\] - 10 \[very severe\]) Duration of morning stiffness (BASDAI Question 6; NRS score 0 \[0 hours\] - 10 \[2 or more hours\]) High-sensitivity C-reactive protein (hs-CRP) in mg/L. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS include Inactive disease (ASDAS \< 1.3) and very high disease (ASDAS \> 3.5). A negative change from Baseline score indicates improvement in disease activity.
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for the Spine at Week 48
In the SPARCC MRI assessment of the spine, the entire spine is evaluated for active inflammation (bone marrow edema). Six discovertebral units (DVU) representing the 6 most abnormal DVUs were selected to calculate the MRI Spine SPARCC score. For each of the 6 DVUs, 3 consecutive sagittal slices were assessed in 4 quadrants to evaluate the extent of inflammation in all three dimensions. Each quadrant was scored for the presence (1) or absence (0) of edema. If edema was present in at least one quadrant of a DVU slice, it was also scored for intensity and depth of the edema representing that slice: An additional score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. Slices that included a lesion demonstrating continuous increased signal of depth ≥ 1 cm extending from the endplate were scored as an additional 1 per slice. The maximum (worst) overall score for all 6 DVUs is 108.
Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Week 48
The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on an 11 point numeric rating scale \[NRS\]) pertaining to symptoms experienced for the past week. For Questions 1 to 5 (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity. A BASDAI 50 response is defined as improvement of 50% or more from Baseline in BASDAI score.
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score
The ASQoL consists of 18 items related to quality of life, including the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. Each item is answered as yes (scored as 1) or no (scored as 0). Scores are summed to obtain the overall score which ranges from 0 to 18, where higher scores indicate a worse quality of life. A negative change from Baseline in ASQoL indicates improvement in quality of life.
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Tongji Hospital
Lead sponsor
Wuhan Central Hospital
Collaborator
Wuhan Hospital of Traditional Chinese Medicine
Collaborator
Novartis
Collaborator
Johns Hopkins Bloomberg School of Public Health
Collaborator
