Clinical trial NCT02437162: A Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNFα Naive Participants With Active Radiographic Axial Spondyloarthritis
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF Alpha Naive Subjects With Active Radiographic Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Keywords: Axial Spondyloarthritis
Ustekinumab
Golimumab
Stelara
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-05-07
Enrollment: 347
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy of ustekinumab, in adult participants with active radiographic axial spondyloarthritis (AxSpA), who are naive to anti-TNF alpha agents, as measured by the reduction in signs and symptoms of radiographic AxSpA.

Detailed description: This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect) study. The study consists of 3 phases; Screening (up to 8 weeks), Treatment phase: placebo-controlled (Week 0 to 24) and active treatment (Week 24 to Week 100), and Safety Follow-up (12 weeks after last dose). Participants will be randomly assigned to 1 of 3 treatment groups: placebo, ustekinumab 45 mg and ustekinumab 90 mg. The total duration of study will be up to 112 weeks. Participants will be primarily assessed for Assessment of SpondyloArthritis International Society (ASAS) 40 response at Week 24. Participants' safety will be monitored throughout the trial.

Eligibility criteria: Inclusion Criteria:

* Participants must have a diagnosis of definite ankylosing spondylitis (AS), as defined by the modified 1984 New York criteria. The radiographic criterion must be confirmed by a central xray reader and at least 1 clinical criterion must be met
* Participants must have symptoms of active disease at screening and at baseline, as evidenced by both a BASDAI score of greater than or equal to (\>=4) and a visual analog scale (VAS) score for total back pain of \>=4, each on a scale of 0 to 10
* Participants with elevated high sensitivity C-reactive protein (hsCRP) level of \>=0.300 milligram per deciliter (mg/dL) at Screening
* If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics for AS, must be on a stable dose for at least 2 weeks prior to the first administration of study agent. If currently not using NSAIDs or other analgesics for AS, must not have received NSAIDs or other analgesics for AS for at least 2 weeks prior to the first administration of the study agent
* A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening and a negative urine pregnancy test at Week 0 before randomization

Exclusion Criteria:

* Participants who have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy, including but not limited to, rheumatoid arthritis, systemic lupus erythematosus, or Lyme disease
* Participants who are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 5 months after receiving the last administration of study agent
* Participants who have received any prior biologic therapy, including but not limited to anti-TNF alpha agents, tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra, ustekinumab, tidrakizumab or other anti-interleukin (IL) 23 biologics, brodalumab, secukinumab, ixekizumab, and B-cell depleting therapies
* Participants who have received any systemic immunosuppressives or disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent. Medications in these categories include, but are not limited to chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine
* Participant who have received leflunomide within 3 months prior to the first administration of study agent (irrespective of undergoing a drug elimination procedure), or have received leflunomide within 12 months prior to the first administration of study agent and have not undergone a drug elimination procedure

Primary outcomes:
measure: Percentage of Participants Who Achieved an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Who Achieved an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
timeFrame: Week 24
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24
timeFrame: Week 24
measure: Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) Total Score at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) Score at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Short Form-(SF)-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in BASDAI Inflammation Score Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS) at Week 16 and 24
timeFrame: Baseline, Week (W) 16 and 24
measure: Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS)-Quantity of Sleep/Optimal Sleep at Week 16 and 24
timeFrame: Baseline, Week (W) 16 and 24
measure: Percentage of Participants With at Least a 40% Improvement From Baseline in ASAS 40 Components at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Achieved at Least 20%, 50%, 70% and 90% Improvement From Baseline in BASDAI Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in BASDAI Total Score Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20
timeFrame: Week 4, 8, 12, 16 and 20
measure: Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20
timeFrame: Week 4, 8, 12, 16 and 20
measure: Percentage of Participants Who Achieved Assessment of Spondyloarthritis International Society (ASAS) Partial Remission Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Percentage of Participants Who Achieved ASAS 5/6 Response at Week 16 and 24
timeFrame: Week 16 and 24
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score ASDAS (CRP) Total Score Through Week 24
timeFrame: Baseline, Week 4, 8, 12 ,16, 20 and 24
measure: Percentage of Participants Who Achieved ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20
timeFrame: Week 4, 8, 12, 16, and 20
measure: Percentage of Participants With ASDAS (CRP) Major Improvement (Decrease >=2.0) Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Percentage of Participants Who Achieved ASDAS (CRP) Clinically Important Improvement (Decrease >=1.1) Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in BASFI at Week 4, 8, 12, 16 and 20
timeFrame: Baseline, Week 4, 8, 12, 16 and 20
measure: Change From Baseline in Chest Expansion at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Total Back Pain (TBP) and Night Back Pain (NBP) Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in Patients Global Assessment of Disease Activity Through Week 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20 and 24
measure: Change From Baseline in European Quality of Life 5 Dimension (EQ-5D) Visual Analog Scale (VAS) Score at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in EQ-5D Index Score at Week 16 and 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Berlin Magnetic Resonance Imaging (MRI) Spine Score at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Percent Work Time Missed Due to AS (Assessed by Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]) Through Week 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Percent Impairment While Working Due to AS (Assessed by WPAI-SHP) Through Week 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Percent Overall Work Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24
timeFrame: Baseline, Week 16 and 24
measure: Change From Baseline in Percent Non-work Activity Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24
timeFrame: Baseline, Week 16 and 24
Other outcomes:
Locations:
city: Peoria
country: United States
state: Arizona
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Eagan
country: United States
state: Minnesota
city: Duncansville
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Jackson
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Mesquite
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Brno
country: Czechia
city: Bruntal
country: Czechia
city: Kladno
country: Czechia
city: Ostrava
country: Czechia
city: Pardubice
country: Czechia
city: Prague 5
country: Czechia
city: Praha 2
country: Czechia
city: Praha 4
country: Czechia
city: Uherske Hradiste
country: Czechia
city: Zlin
country: Czechia
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Bydgoszcz
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Chelyabinsk
country: Russian Federation
city: Chita
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Kirov
country: Russian Federation
city: Kursk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Sankt-Petersburg.
country: Russian Federation
city: Saratov
country: Russian Federation
city: St.Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Ufa
country: Russian Federation
city: Ulyanovsk
country: Russian Federation
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Ternopil
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Zaporizhzhya
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Deodhar A, Gensler LS, Sieper J, Clark M, Calderon C, Wang Y, Zhou Y, Leu JH, Campbell K, Sweet K, Harrison DD, Hsia EC, van der Heijde D. Three Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Feb;71(2):258-270. doi: 10.1002/art.40728. Epub 2018 Dec 29.