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NCT04156620

Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

Completed Phase 3 Results posted Last updated 18 June 2024
What this trial tests

Phase 3 trial testing Secukinumab in Ankylosing Spondylitis in 527 participants. Completed in 20 December 2022.

Timeline
11 December 2019
Primary endpoint
17 February 2022
20 December 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment527
Start date11 December 2019
Primary completion17 February 2022
Estimated completion20 December 2022
Sites102 locations across Italy, Colombia, Russia, Greece, Malaysia, India, Belgium, Sweden

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Ankylosing Spondylitis. 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 Who Achieved an ASAS40 (Assessment of SpondyloArthritis International Society Criteria) Primary · Baseline to Week 16

ASAS40 is ≥ 40% and an absolute improvement from baseline of ≥20 units (range 0-100) in ≥ 3 of the following 4 domains: back pain \[10 cm visual analogue scale (VAS)\], patient global assessment of disease activity (10 cm VAS), physical function (BASFI; range 0-100) and inflammation (mean score of items 5 and 6 of the BASDAI; both 10 cm VAS) without any worsening in the remaining domain. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented b

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.40.8534.94 – 46.76
Placebo - AIN457 3 mg/kg i.v.22.9417.86 – 28.02
Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Major Improvement Secondary · Baseline to Week 16

ASDAS-CRP was utilized to assess disease activity status. Parameters used for the ASDAS included: total back pain (BASDAI question 2), patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and CRP in mg/L. Disease activity states: inactive disease, moderate disease activity, high disease activity, and very high disease activity. The three values selected to separate these states are: \< 1.3 between inactive disease and moderate disease activity; \< 2.1 between moderate disease activity and high disease a

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.27.9922.86 – 33.12
Placebo - AIN457 3 mg/kg i.v.7.544.44 – 10.64
The Change From Baseline in Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Secondary · Baseline to Week 16

BASDAI consists of a 0 through 10 scale (0 indicating no problem and 10 indicating the worst problem, captured as a continuous VAS), which was used to answer six questions pertaining to the five major symptoms of AS: fatigue, spinal pain, peripheral joint pain / swelling,, areas of localized tenderness (enthesitis, or inflammation of tendons and ligaments), morning stiffness duration, morning stiffness severity. To give each symptom equal weight, the mean of the two scores relating to morning stiffness is taken into account (questions 5 and 6). The resulting 0 to 10 score is added to the scor

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.-2.70± 0.144
Placebo - AIN457 3 mg/kg i.v.-1.69± 0.144
Percentage of Participants Who Achieved an ASAS 5/6 (Assessment of Spondylarthritis International Society Criteria) Secondary · Baseline to Week 16

The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains. A higher score on the VAS signifies higher severity. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represe

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.43.9237.94 – 49.90
Placebo - AIN457 3 mg/kg i.v.21.7716.77 – 26.77
The Change From Baseline in Total Bath Ankylosing Spondylitis Functional Index (BASFI) Secondary · Baseline to Week 16

The BASFI is a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The questions were chosen on the basis of predominant input from subjects with AS. The first eight questions consider activities related to functional anatomy. The final two questions assess the subjects' ability to cope with everyday life. A 0-10 scale (captured as a continuous VAS) is used to answer the questions. The BASFI score is the mean of the ten scales - a value between 0 and 10.

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.-2.33± 0.147
Placebo - AIN457 3 mg/kg i.v.-1.39± 0.148
The Change From Baseline in Short Form-36 Physical Component Summary (SF-36 PCS) Secondary · Baseline to Week 16

The Short Form-36 Physical Component Summary (SF-36 PCS) is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consists of eight subscales (domains) that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role- Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The eight domains are based on a scale from 0-100 while PCS and MCS are norm-bas

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.7.70± 0.473
Placebo - AIN457 3 mg/kg i.v.4.69± 0.473
The Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQol) Secondary · Baseline to Week 16

The ASQoL is a self-administered questionnaire designed to assess health-related quality of life in adult subjects with AS. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response, resulting in overall scores that range from 0 (least severity) to 18 (highest severity). As such, lower scores indicate better quality of life. Items include an assessment of mobility/energy, self care and mood/emotion. The recall period is "at the moment".

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.-4.65± 0.291
Placebo - AIN457 3 mg/kg i.v.-2.88± 0.290
The Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Secondary · Baseline to Week 16

This assessment (laboratory assessment) was performed in order to identify the presence of inflammation, to determine its severity and to monitor the response to treatment. Exponentially transformed LSM, the geometric mean ratio of post-baseline/baseline. A value \<1 indicates a reduced CRP

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.0.39± 1.063
Placebo - AIN457 3 mg/kg i.v.0.89± 1.062
Percentage of Participants Who Achieved an ASAS20 (Assessment of SpondyloArthritis International Society Criteria) Secondary · Baseline to Week 16

The ASAS Response Criteria (ASAS20) is defined as an improvement of ≥20% and ≥1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain. A higher score on the VAS signifies higher severity. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean durati

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.63.9458.19 – 69.70
Placebo - AIN457 3 mg/kg i.v.40.5334.62 – 46.44
The Percentage of Participants Achieving Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Inactive Disease. Secondary · Baseline to Week 16

ASDAS-CRP was utilized to assess disease activity status. Parameters used for the ASDAS included: total back pain (BASDAI question 2), patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and CRP in mg/L. Disease activity states: inactive disease, moderate disease activity, high disease activity, and very high disease activity. The three values selected to separate these states are: \< 1.3 between inactive disease and moderate disease activity; \< 2.1 between moderate disease activity and high disease

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.15.6611.53 – 19.78
Placebo - AIN457 3 mg/kg i.v.3.081.00 – 5.15
Percentage of Participants Who Achieved ASAS20 (Assessment of Spondylarthritis International Society Criteria) Partial Remission. Secondary · Baseline to Week 16

ASAS partial remission criteria are defined as a value not above 2 units in each of the four main ASAS domains on a scale of 0-10. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Met

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.14.7610.49 – 19.03
Placebo - AIN457 3 mg/kg i.v.4.201.77 – 6.63
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Secondary · Baseline to Week 16

The PSQI is a self-report questionnaire that assesses sleep quality over a 1-month time interval. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then ca

GroupValue95% CI
AIN457 6 mg/kg - 3 mg/kg i.v.-2.42± 0.222
Placebo - AIN457 3 mg/kg i.v.-1.76± 0.221

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were reported for a maximum of 478 days for participants on AIN457 (including placebo switchers) and 182 days for participants on placebo which includes the 84 days in safety follow up.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Any AIN457
Serious: 32/517 (6%)
Deaths: 1/517
Placebo Until Week 16
Serious: 3/261 (1%)
Deaths: 0/261

Serious adverse events (37 terms)

ReactionSystemAny AIN457Placebo Until Week 16
Myocardial infarctionCardiac disorders
Abdominal painGastrointestinal disorders
Colitis ulcerativeGastrointestinal disorders
CellulitisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Acute left ventricular failureCardiac disorders
Coronary artery occlusionCardiac disorders
TachycardiaCardiac disorders
Tympanic membrane perforationEar and labyrinth disorders
ChoroiditisEye disorders
ColitisGastrointestinal disorders
Crohn's diseaseGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Chest painGeneral disorders
Non-cardiac chest painGeneral disorders
CholecystitisHepatobiliary disorders
Drug hypersensitivityImmune system disorders
Anal abscessInfections and infestations
AppendicitisInfections and infestations
COVID-19 pneumoniaInfections and infestations
Dengue feverInfections and infestations
Lower respiratory tract infectionInfections and infestations
Parainfluenzae virus infectionInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
Other adverse events (10 terms — click to expand)

ReactionSystemAny AIN457Placebo Until Week 16
COVID-19Infections and infestations
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
PharyngitisInfections and infestations
NauseaGastrointestinal disorders
RhinitisInfections and infestations
Urinary tract infectionInfections and infestations

Most-reported serious reactions: Myocardial infarction, Abdominal pain, Colitis ulcerative, Cellulitis, Anaemia, Acute left ventricular failure, Coronary artery occlusion, Tachycardia.

Data from ClinicalTrials.gov NCT04156620 adverse events section.

Sponsor's own description

The purpose of this global study was to demonstrate the efficacy, safety, and tolerability of an intravenous (i.v.) regimen of secukinumab compared to placebo in participants with active ankylosing spondylitis (AS) or non-radiographic axial spondyloarthritis (nr-axSpA ) at Week 16 despite current or previous non-steroidal anti inflammatory drugs (NSAID), disease-modifying antirheumatic drugs (DMARD) and/or anti Tumor Necrosis Factor (TNF) therapy. In addition, to further support efficacy and safety of an i.v. regimen, data was collected for up to 52 weeks of treatment.

Publications & conference data

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

  1. Targeted Immunotherapy for Autoimmune Disease.
    Jung SM, Kim WU. · · 2022 · cited 113× · PMID 35291650 · DOI 10.4110/in.2022.22.e9
  2. Recent advances in managing axial spondyloarthritis.
    Agrawal P, Machado PM. · · 2020 · cited 6× · PMID 32704350 · DOI 10.12688/f1000research.22577.1
  3. Efficacy and Safety of Intravenous Secukinumab in Patients With Active Axial Spondyloarthritis: Results From a Randomized, Placebo-Controlled, Phase 3 Study.
    Deodhar A, Supronik J, Kivitz A, Valenzuela G, et al · · 2025 · cited 4× · PMID 39300513 · DOI 10.1002/art.42993
  4. 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
  5. Model-Informed Drug Development-Based Approval of Intravenous Secukinumab for the Treatment of Adult Patients with Active Psoriatic Arthritis, Active Ankylosing Spondylitis, and Active Non-Radiographic Axial Spondyloarthritis.
    Pisal DS, Li Y, Golding A, Nair R, et al · · 2025 · cited 3× · PMID 39411974 · DOI 10.1002/cpt.3464
  6. A Narrative Review of Secukinumab in Spondyloarthritis and Psoriatic Arthritis: Treating the Whole Patient.
    Kaeley GS, Kivitz A, Mease P, Weiss PF, et al · · 2026 · PMID 41854828 · DOI 10.1007/s40744-026-00833-6
  7. Model-Informed Drug Development-Based Bridging from Subcutaneous to Intravenous Secukinumab Dosing: Approval in Psoriatic Arthritis and Axial Spondyloarthritis.
    Dumortier T, Valenzuela G, Churchill M, Mijatovic J, et al · · 2025 · PMID 40454543 · DOI 10.1002/cpt.3716

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04156620.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing