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NCT02407223

An Efficacy and Safety Study of Ustekinumab in Participants With Active Nonradiographic Axial Spondyloarthritis

Terminated Phase 3 Results posted Last updated 13 March 2019
What this trial tests

Phase 3 trial testing Group 1: Placebo in Nonradiographic Axial Spondylitis, Ankylosing in 356 participants. Terminated before completion.

Timeline
13 July 2015
Primary endpoint
26 September 2017
26 September 2017

Quick facts

Lead sponsorJanssen Research & Development, LLC
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment356
Start date13 July 2015
Primary completion26 September 2017
Estimated completion26 September 2017
Sites90 locations across France, Russia, Ukraine, Belgium, Taiwan, United Kingdom, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 18 to 50, any sex, with Nonradiographic Axial Spondylitis, Ankylosing. 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 Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24 Primary · Week 24

ASAS 20 defined as improvement of greater than or equal to (\>=) 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 centimeter(cm) scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very

GroupValue95% CI
Placebo47.6
Ustekinumab 45 mg55.4
Ustekinumab 90 mg49.4
Percentage of Participants Who Achieved an ASAS 40 Response at Week 24 Secondary · Week 24

ASAS 40 defined as improvement of \>= 40% from baseline and absolute improvement from baseline of at least 2 on 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor),total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10 cm; 0=none,10=very severe); no worsening at

GroupValue95% CI
Placebo25.6
Ustekinumab 45 mg33.7
Ustekinumab 90 mg28.2
Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 Secondary · Week 24

The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness were added to the total of the remaining 4 scores, and the final BASDAI score (ranging 0-

GroupValue95% CI
Placebo23.2
Ustekinumab 45 mg32.5
Ustekinumab 90 mg25.9
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 Secondary · Baseline, Week 24

The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) 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 ankylosing spondylitis participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. 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. Higher BASFI score indicat

GroupValue95% CI
Placebo-2.11± 2.371
Ustekinumab 45 mg-2.28± 2.625
Ustekinumab 90 mg-1.90± 2.731
Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24 Secondary · Week 24

ASDAS includes CRP milligram per liter (mg/L); four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale \[NRS\]) included total back pain(TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment(PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121\*total back pain)+ (0.110\*PGA)+ (0.073\*peripheral pain/swelling)+ (0.058\* DMS)+ (0.579\*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being

GroupValue95% CI
Placebo7.3
Ustekinumab 45 mg14.5
Ustekinumab 90 mg12.9
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24 Secondary · Baseline, Week 4, 8, 12, 16, 20 and 24

Change from baseline in hsCRP levels was reported. hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing). Here 'n' signifies the number of participants who were analyzed at each specified timepoints, for each arm, respectively.

Change at Week 4
GroupValue95% CI
Placebo-0.08± 1.567
Ustekinumab 45 mg-0.10± 2.574
Ustekinumab 90 mg-0.39± 1.601
Change at Week 8
GroupValue95% CI
Placebo-0.23± 1.490
Ustekinumab 45 mg-0.53± 2.084
Ustekinumab 90 mg-0.57± 2.209
Change at Week 12
GroupValue95% CI
Placebo-0.23± 1.661
Ustekinumab 45 mg-0.71± 2.392
Ustekinumab 90 mg-0.61± 2.534
Change at Week 16
GroupValue95% CI
Placebo-0.49± 1.725
Ustekinumab 45 mg-0.63± 2.211
Ustekinumab 90 mg-0.61± 2.539
Change at Week 20
GroupValue95% CI
Placebo-0.36± 1.951
Ustekinumab 45 mg-0.78± 2.353
Ustekinumab 90 mg-0.76± 2.383
Change at Week 24
GroupValue95% CI
Placebo-0.42± 2.145
Ustekinumab 45 mg-0.63± 2.402
Ustekinumab 90 mg-0.78± 2.413
Percentage of Participants With ASAS 20 Components at Week 24 Secondary · Week 24

ASAS 20 defined as \>= 20% improvement from baseline in 4 individual components of ASAS20: Patient's global assessment (PGA) of disease activity (0 to 10cm; 0=very well,10=very poor), total back pain(0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean(0 to10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to functional anatomy and 2 relate to participant's ability to cope with life) and Inflammation (0 to 10cm;0=none,10=very severe).

>=20% improvement from baseline in PGA score
GroupValue95% CI
Placebo64.1
Ustekinumab 45 mg61.3
Ustekinumab 90 mg58.8
>=20% improvement from baseline in total back pain
GroupValue95% CI
Placebo62.8
Ustekinumab 45 mg60.0
Ustekinumab 90 mg60.0
>=20% improvement from baseline in BASFI
GroupValue95% CI
Placebo53.8
Ustekinumab 45 mg57.5
Ustekinumab 90 mg56.3
>=20% improvement from baseline in inflammation
GroupValue95% CI
Placebo64.1
Ustekinumab 45 mg66.3
Ustekinumab 90 mg65.0
Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20 Secondary · Week 4, 8, 12, 16 and 20

ASAS 40 defined as improvement of \>= 40% from baseline and absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all fr

Week 4
GroupValue95% CI
Placebo3.7
Ustekinumab 45 mg8.4
Ustekinumab 90 mg11.8
Week 8
GroupValue95% CI
Placebo18.3
Ustekinumab 45 mg19.3
Ustekinumab 90 mg18.8
Week 12
GroupValue95% CI
Placebo17.1
Ustekinumab 45 mg27.7
Ustekinumab 90 mg24.7
Week 16
GroupValue95% CI
Placebo19.5
Ustekinumab 45 mg27.7
Ustekinumab 90 mg24.7
Week 20
GroupValue95% CI
Placebo24.4
Ustekinumab 45 mg38.6
Ustekinumab 90 mg32.9
Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20 Secondary · Week 4, 8, 12, 16 and 20

ASAS 20 defined as improvement of \>= 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>=

Week 4
GroupValue95% CI
Placebo23.2
Ustekinumab 45 mg26.5
Ustekinumab 90 mg32.9
Week 8
GroupValue95% CI
Placebo31.7
Ustekinumab 45 mg41.0
Ustekinumab 90 mg36.5
Week 12
GroupValue95% CI
Placebo34.1
Ustekinumab 45 mg48.2
Ustekinumab 90 mg41.2
Week 16
GroupValue95% CI
Placebo40.2
Ustekinumab 45 mg49.4
Ustekinumab 90 mg35.3
Week 20
GroupValue95% CI
Placebo45.1
Ustekinumab 45 mg59.0
Ustekinumab 90 mg44.7
Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20 Secondary · Week 4, 8, 12, 16, and 20

The BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), and morning stiffness (2 questions: duration and severity). Each question is an easy to answer 10 centimeter (cm) visual analog scale (VAS), with 0 being none, and 10 being very severe. In order to give each of the 5 symptoms equal weight, the mean of the 2 questions about morning stiffness will be added to the total of the remaining 4 scores, and the final BASDAI score (ranging

Week 4
GroupValue95% CI
Placebo4.9
Ustekinumab 45 mg8.4
Ustekinumab 90 mg8.2
Week 8
GroupValue95% CI
Placebo9.8
Ustekinumab 45 mg15.7
Ustekinumab 90 mg17.6
Week 12
GroupValue95% CI
Placebo18.3
Ustekinumab 45 mg16.9
Ustekinumab 90 mg28.2
Week 16
GroupValue95% CI
Placebo19.5
Ustekinumab 45 mg21.7
Ustekinumab 90 mg24.7
Week 20
GroupValue95% CI
Placebo15.9
Ustekinumab 45 mg28.9
Ustekinumab 90 mg32.9
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 4, 8, 12, 16 and 20 Secondary · Baseline, Week 4, 8, 12, 16 and 20

The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) 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. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. 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. Higher BASFI score indicates more severe funct

Change at Week 4
GroupValue95% CI
Placebo-0.60± 1.582
Ustekinumab 45 mg-1.15± 1.748
Ustekinumab 90 mg-0.79± 1.600
Change at Week 8
GroupValue95% CI
Placebo-0.82± 1.997
Ustekinumab 45 mg-1.54± 2.177
Ustekinumab 90 mg-1.05± 2.095
Change at Week 12
GroupValue95% CI
Placebo-1.00± 2.064
Ustekinumab 45 mg-1.69± 2.079
Ustekinumab 90 mg-1.35± 2.458
Change at Week 16
GroupValue95% CI
Placebo-1.05± 2.162
Ustekinumab 45 mg-1.75± 2.312
Ustekinumab 90 mg-1.17± 2.747
Change at Week 20
GroupValue95% CI
Placebo-1.70± 2.339
Ustekinumab 45 mg-2.11± 2.394
Ustekinumab 90 mg-1.64± 2.794
Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16, and 20 Secondary · Week 4, 8, 12, 16, and 20

ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale \[NRS\]) included total back pain(TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment(PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121\*total back pain)+ (0.110\*PGA)+ (0.073\*peripheral pain/swelling)+ (0.058\* DMS)+ (0.579\*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 represent

Week 4
GroupValue95% CI
Placebo2.4
Ustekinumab 45 mg3.6
Ustekinumab 90 mg1.2
Week 8
GroupValue95% CI
Placebo6.1
Ustekinumab 45 mg7.2
Ustekinumab 90 mg9.4
Week 12
GroupValue95% CI
Placebo4.9
Ustekinumab 45 mg4.8
Ustekinumab 90 mg10.6
Week 16
GroupValue95% CI
Placebo6.1
Ustekinumab 45 mg7.2
Ustekinumab 90 mg11.8
Week 20
GroupValue95% CI
Placebo3.7
Ustekinumab 45 mg13.3
Ustekinumab 90 mg15.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately up to 2.2 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Only
Serious: 2/116 (2%)
Deaths: 0/116
Placebo to Ustekinumab 45mg
Serious: 0/42 (0%)
Deaths: 0/42
Placebo to Ustekinumab 90mg
Serious: 2/40 (5%)
Deaths: 0/40
Ustekinumab 45mg Only
Serious: 2/118 (2%)
Deaths: 0/118
Ustekinumab 90mg Only
Serious: 6/122 (5%)
Deaths: 0/122

Serious adverse events (11 terms)

ReactionSystemPlacebo OnlyPlacebo to Ustekinumab 45mgPlacebo to Ustekinumab 90mgUstekinumab 45mg OnlyUstekinumab 90mg Only
UveitisEye disorders
Inguinal HerniaGastrointestinal disorders
Chronic SinusitisInfections and infestations
GastroenteritisInfections and infestations
Ankle FractureInjury, poisoning and procedural complications
Axial SpondyloarthritisMusculoskeletal and connective tissue disorders
SpondyloarthropathyMusculoskeletal and connective tissue disorders
Panic AttackPsychiatric disorders
NephrolithiasisRenal and urinary disorders
Haemorrhagic Ovarian CystReproductive system and breast disorders
MenorrhagiaReproductive system and breast disorders
Other adverse events (9 terms — click to expand)

ReactionSystemPlacebo OnlyPlacebo to Ustekinumab 45mgPlacebo to Ustekinumab 90mgUstekinumab 45mg OnlyUstekinumab 90mg Only
Viral Upper Respiratory Tract InfectionInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
Alanine Aminotransferase IncreasedInvestigations
FatigueGeneral disorders
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back PainMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
SinusitisInfections and infestations

Most-reported serious reactions: Uveitis, Inguinal Hernia, Chronic Sinusitis, Gastroenteritis, Ankle Fracture, Axial Spondyloarthritis, Spondyloarthropathy, Panic Attack.

Data from ClinicalTrials.gov NCT02407223 adverse events section.

Sponsor's own description

The purpose of this study is to assess the efficacy and safety of ustekinumab in adult participants with active nonradiographic axial spondyloarthritis (nr-AxSpA) measured by the reduction in signs and symptoms of nonradiographic axial spondyloarthritis (nr-AxSpA).

Publications & conference data

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

  1. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases.
    Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. · · 2016 · cited 474× · PMID 26633291 · DOI 10.1038/nrrheum.2015.167
  2. Drug development in the era of precision medicine.
    Dugger SA, Platt A, Goldstein DB. · · 2018 · cited 296× · PMID 29217837 · DOI 10.1038/nrd.2017.226
  3. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study.
    Baeten D, Østergaard M, Wei JC, Sieper J, et al · · 2018 · cited 268× · PMID 29945918 · DOI 10.1136/annrheumdis-2018-213328
  4. Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders.
    Fasching P, Stradner M, Graninger W, Dejaco C, et al · · 2017 · cited 178× · PMID 28098832 · DOI 10.3390/molecules22010134
  5. Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation?
    Siebert S, Millar NL, McInnes IB. · · 2019 · cited 67× · PMID 30297330 · DOI 10.1136/annrheumdis-2018-213654
  6. The Initiation, but Not the Persistence, of Experimental Spondyloarthritis Is Dependent on Interleukin-23 Signaling.
    van Tok MN, Na S, Lao CR, Alvi M, et al · · 2018 · cited 62× · PMID 30038617 · DOI 10.3389/fimmu.2018.01550
  7. Targeting the interleukin-23/17 axis in axial spondyloarthritis.
    Paine A, Ritchlin CT. · · 2016 · cited 45× · PMID 27152702 · DOI 10.1097/bor.0000000000000301
  8. Targeting inflammatory pathways in axial spondyloarthritis.
    Furst DE, Louie JS. · · 2019 · cited 34× · PMID 31164157 · DOI 10.1186/s13075-019-1885-z

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