NCT04285229

A Study of Ixekizumab (LY2439821) in Chinese Participants With Radiographic Axial Spondyloarthritis

Completed Phase 3 Results posted Last updated 14 April 2023

What this trial tests

Phase 3 trial testing Ixekizumab in Spondyloarthritis in 147 participants. Completed in 17 March 2022.

Timeline

10 April 2020

Primary endpoint
31 March 2021

17 March 2022

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	147
Start date	10 April 2020
Primary completion	31 March 2021
Estimated completion	17 March 2022
Sites	19 locations across China

Drugs / interventions tested

• Ixekizumab (ixekizumab) — full drug profile →
• Placebo

Conditions studied

• Spondyloarthritis — all drugs for Spondyloarthritis →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Spondyloarthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response in Biological Disease-modifying Antirheumatic Drug (bDMARD)-naïve Participants Primary · Week 16

ASAS40 is defined as improvement from baseline of greater than or equal to (\>=) 40 % and absolute improvement from baseline of at least 2 units (range of 0 to 10) in at least 3 of the following 4 domains without any worsening in the remaining domain. 1. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). 2. Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3. Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the diffic

Group	Value	95% CI
Placebo	7.8
Ixekizumab 80mg Q4W	40.9

Percentage of Participants Achieving an ASAS40 Response Secondary · Week 16

ASAS40 is defined as improvement from baseline of greater than or equal to (\>=) 40 % and absolute improvement from baseline of at least 2 units (range of 0 to 10) in at least 3 of the following 4 domains without any worsening in the remaining domain. 1. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). 2. Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3. Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the diffic

Group	Value	95% CI
Placebo	8.2
Ixekizumab 80mg Q4W	37.8

Percentage of Participants Achieving an ASAS20 Response Secondary · Week 16

ASAS20 response is defined as a ≥20% improvement and an absolute improvement from baseline of ≥1 units (range 0 to 10) in ≥3 of 4 domains, and no worsening of ≥20% and ≥1 unit (range 0 to 10) in the remaining domain. 1. Patient Global: How active was your spondylitis on average during the last week? score ranges 0 (not active) to 10 (very active). 2. Spinal Pain: How much Pain of your spine due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3. Bath Ankylosing Spondylitis Functional Index (BASFI): Participant asked to rate the difficulty associated with 10 individual

Group	Value	95% CI
Placebo	35.6
Ixekizumab 80mg Q4W	59.5

Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) Secondary · Baseline, Week 16

ASDAS is a composite index to assess disease activity in AS. The parameters used for the ASDAS (with CRP as acute phase reactant) are 1. Total back pain 2. Patient global 3. Peripheral pain/swelling 4. Duration of morning stiffness and 5. CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to y

Group	Value	95% CI
Placebo	-0.19	± 0.103
Ixekizumab 80mg Q4W	-1.33	± 0.100

Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Response Secondary · Baseline, Week 16

The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to radiographic axial spondyloarthritis (rad-axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. LS mean was determined by MMRM with treatment, baseline CRP status, TNF inhibitors

Group	Value	95% CI
Placebo	-0.90	± 0.231
Ixekizumab 80mg Q4W	-2.39	± 0.226

Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Secondary · Baseline, Week 16

The BASFI is a participant-reported assessment that establishes a participant's functional baseline and subsequent response to treatment. The BASFI is composed with 10 questions to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Participants respond to each question using an NRS scale (range 0 to 10). The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10, with a higher score indicating

Group	Value	95% CI
Placebo	-0.49	± 0.237
Ixekizumab 80mg Q4W	-1.36	± 0.230

Change From Baseline in Magnetic Resonance Imaging (MRI) of the Spine (Spondyloarthritis Research Consortium of Canada [SPARCC] Score) Secondary · Baseline, Week 16

MRI score of spine was assessed using SPARCC method. All 23 disco-vertebral units (DVU) of the spine (from C2 to S1) were scored for bone marrow edema. A single DVU has 18 scoring units, and each has score of 0 or 1, bringing the maximum total score to 414, the sum ranges from 0 to 414 with higher scores reflecting worse disease. Scoring was performed by central readers. LS mean was determined by ANCOVA with factors for treatment, baseline CRP status, TNF inhibitors experience, and baseline value.

Group	Value	95% CI
Placebo	-0.93	± 1.550
Ixekizumab 80mg Q4W	-8.65	± 1.507

Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score Secondary · Baseline, Week 16

SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher sc

Group	Value	95% CI
Placebo	1.23	± 0.740
Ixekizumab 80mg Q4W	3.85	± 0.716

Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score Secondary · Baseline, Week 16

SF-36 consists of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function, and vitality. The patient's responses are solicited using Likert scales that vary in length, with 3-6 response options per item. The SF-36 can be scored into the 8 health domains named above and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. The domain and summary scores range from 0 to 100; higher sc

Group	Value	95% CI
Placebo	-0.06	± 1.027
Ixekizumab 80mg Q4W	0.45	± 1.003

Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP) Secondary · Baseline, Week 16

High sensitivity CRP is the measure of acute phase reactant. It was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. High sensitivity CRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. LS mean was determined by MMRM with treatment, baseline CRP status, TNF inhibitors experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.

Group	Value	95% CI
Placebo	2.65	± 1.349
Ixekizumab 80mg Q4W	-10.10	± 1.312

Change From Baseline in Mobility on the Bath Ankylosing Spondylitis Metrology Index (BASMI) Secondary · Baseline, Week 16

BASMI is a combined index comprising of 5 clinical measurements of spinal mobility in patients with radiographic axial spondyloarthritis (rad-axSpA). 1. Lateral Spinal Flexion 2. Tragus-to-wall distance 3. Lumbar Flexion (modified Schober) 4. Maximal intermalleolar distance and 5. Cervical rotation. The BASMI linear result is the average of the 5 assessments and ranges from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their AS. LS mean was determined by MMRM with treatment, baseline CRP status, TNF inhibitors experience, baseline value, visit

Group	Value	95% CI
Placebo	0.06	± 0.093
Ixekizumab 80mg Q4W	-0.30	± 0.090

Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) Secondary · Baseline, Week 16

The MASES is an index used to measure the severity of enthesitis. The MASES assesses 13 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include costochondral 1 (right/left), costochondral 7 (right/left), spinal iliaca anterior superior (right/left), crista iliaca (right/left), spina iliaca posterior (right/left), processus spinosus L5, and Achilles tendon proximal insertion (right/left). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was determined by MMRM with treatment, baseline CRP

Group	Value	95% CI
Placebo	-1.06	± 0.349
Ixekizumab 80mg Q4W	-1.77	± 0.361

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to Follow-up (Up To 64 Weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/73 (1%)

Deaths: 0/73

Ixekizumab 80mg Q4W

Serious: 2/74 (3%)

Deaths: 0/74

Placebo/Ixekizumab 80mg Q4W - Extended Treatment Period

Serious: 6/70 (9%)

Deaths: 0/70

Ixekizumab 80mg Q4W/Ixekizumab 80mg Q4W - Extended Treatment Period

Serious: 4/72 (6%)

Deaths: 0/72

Placebo - Follow-up Period

Serious: 0/1 (0%)

Deaths: 0/1

Ixekizumab 80mg Q4W - Follow-up Period

Serious: 1/135 (1%)

Deaths: 0/135

Serious adverse events (15 terms)

Reaction	System	Placebo	Ixekizumab 80mg Q4W	Placebo/Ixekizumab 80mg Q4…	Ixekizumab 80mg Q4W/Ixekiz…	Placebo - Follow-up Period	Ixekizumab 80mg Q4W - Foll…
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Kidney infection	Infections and infestations	—	—	—	—	—	—
Male genital tract tuberculosis	Infections and infestations	—	—	—	—	—	—
Pulmonary tuberculosis	Infections and infestations	—	—	—	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Vestibular neuronitis	Infections and infestations	—	—	—	—	—	—
Auricular haematoma	Injury, poisoning and procedural complications	—	—	—	—	—	—
Brain contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—
Hand fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Benign connective tissue neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Drug eruption	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Shock	Vascular disorders	—	—	—	—	—	—
Varicose vein	Vascular disorders	—	—	—	—	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Placebo	Ixekizumab 80mg Q4W	Placebo/Ixekizumab 80mg Q4…	Ixekizumab 80mg Q4W/Ixekiz…	Placebo - Follow-up Period	Ixekizumab 80mg Q4W - Foll…
Injection site reaction	General disorders	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—	—	—	—	—
Hyperlipidaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Weight increased	Investigations	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—
Protein urine present	Investigations	—	—	—	—	—	—
Vaginal infection	Infections and infestations	—	—	—	—	—	—
Pelvic fluid collection	Reproductive system and breast disorders	—	—	—	—	—	—

Most-reported serious reactions: Upper gastrointestinal haemorrhage, Kidney infection, Male genital tract tuberculosis, Pulmonary tuberculosis, Pyelonephritis acute, Urinary tract infection, Vestibular neuronitis, Auricular haematoma.

Data from ClinicalTrials.gov NCT04285229 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate the efficacy and safety of ixekizumab in Chinese participants with radiographic axial spondyloarthritis (r-axSpA).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Matching-Adjusted Indirect Comparison of the 52-Week Efficacy of Bimekizumab Versus Secukinumab and Ixekizumab for the Treatment of Radiographic Axial Spondyloarthritis.
   Maksymowych WP, Thom H, Mørup MF, Taieb V, et al · · 2024 · cited 6× · PMID 38916823 · DOI 10.1007/s40744-024-00684-z
2. Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study.
   Xue Y, Hu J, Liu D, Li J, et al · · 2024 · cited 5× · PMID 37737952 · DOI 10.1007/s40259-023-00625-2
3. Interleukin-17 Inhibitors for the Treatment of Ankylosing Spondylitis.
   Huang JX, Zhang LJ, Wei JC. · · 2020 · cited 4× · PMID 36465082 · DOI 10.2478/rir-2020-0004
4. Rapid and Sustained Effect of Ixekizumab on Patient Global, Spinal Pain, Stiffness, and Fatigue in Chinese Patients with Radiographic Axial Spondyloarthritis.
   Zhu X, Hu J, Liu D, Li J, et al · · 2024 · cited 2× · PMID 38907104 · DOI 10.1007/s40744-024-00688-9
5. Efficacy of Ixekizumab in Chinese Patients with Radiographic Axial Spondyloarthritis by Baseline C-Reactive Protein Level.
   Kong N, Hu J, Liu D, Li J, et al · · 2025 · cited 1× · PMID 40343690 · DOI 10.1007/s40744-025-00765-7
6. Efficacy of Ixekizumab in Radiographic Axial Spondyloarthritis by Baseline C-Reactive Protein Level: A Pooled Analysis of Phase III Trials.
   Sengupta R, Machado PM, Goupille P, Rudwaleit M, et al · · 2026 · PMID 42228347 · DOI 10.1007/s40744-026-00862-1
7. Efficacy of Ixekizumab in Chinese Patients with Radiographic-Axial Spondyloarthritis by Baseline Inflammation Status on Magnetic Resonance Imaging.
   Zhu X, Hu J, Liu D, Li J, et al · · 2026 · PMID 41495585 · DOI 10.1007/s40744-025-00819-w
8. The Efficacy and Safety of Subcutaneous Ixekizumab for the Treatment of Axial Spondylarthritis: A Systematic Review and Meta-Analysis.
   Alzahrani Z, Bashrahil BA, Alzahrani R, Alharthy F. · · 2023 · PMID 36974243 · DOI 10.7759/cureus.35360