Clinical trial NCT02438787: A Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory 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) Refractory Subjects With Active Radiographic Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Keywords: Ankylosing Spondylitis
Ustekinumab
Golimumab
STELARA
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-05-08
Enrollment: 315
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 anti-TNF(alpha) refractory participants with active radiographic axial spondyloarthritis (AxSpA), 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 52), and Safety Follow-up (up to 12 weeks). 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 64 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 Bath Ankylosing Spondylitis Disease Activity Index (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
* Refractory by either lack of benefit or documented intolerance to 1 and no more than 1 anti-TNF(alpha) agent
* Inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over a 4-week period in total with maximal doses of NSAID(s), or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs.
* Participants with complete ankylosis of the spine are permitted to be included in the study, but will be limited to approximately 10 percent (%) of the study population

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 have received infliximab or infliximab biosimilar, within 12 weeks of the first study agent administration; have received adalimumab, adalimumab biosimilar, or certolizumab pegol within 6 weeks of the first study agent administration; have received etanercept or etanercept biosimilar within 6 weeks of the first study agent administration
* Participants who have ever received golimumab
* 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 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 leflunomide, chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine

Primary outcomes:
measure: Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24
timeFrame: Week(W) 24
Secondary outcomes:
measure: Percentage of Participants Who Achieved an 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: Percentage of Participants With 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 Who Achieved ASAS 40 Responses at Week 4, 8, 12, 16 and 20
timeFrame: Week 4, 8, 12, 16 and 20
measure: Percentage of Participants Who Achieved ASAS 20 Responses at Week 4, 8, 12, 16 and 20
timeFrame: Week 4, 8, 12, 16 and 20
measure: Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20
timeFrame: Week 4, 8, 12, 16 and 20
measure: Change From Baseline in BASFI Total Score at Week 4, 8, 12, 16 and 20
timeFrame: Baseline, Week 4, 8, 12, 16 and 20
Other outcomes:
Locations:
city: Glendale
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Fremont
country: United States
state: California
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Monroe
country: United States
state: Louisiana
city: Eagan
country: United States
state: Minnesota
city: Orchard Park
country: United States
state: New York
city: Portland
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Jackson
country: United States
state: Tennessee
city: Austin
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state: Texas
city: Mesquite
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Ciudad de Buenos Aires
country: Argentina
city: Ciudad De La Plata
country: Argentina
city: Ciudad De San Miguel De Tucuman
country: Argentina
city: Cordoba
country: Argentina
city: Bruxelles
country: Belgium
city: Genk
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liège
country: Belgium
city: Merksem (Antwerp)
country: Belgium
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Goiania
country: Brazil
city: Juiz de Fora
country: Brazil
city: Porto Alegre
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Santo Andre
country: Brazil
city: São Paulo
country: Brazil
city: Burgas
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Victoria
country: Canada
state: British Columbia
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Toronto
country: Canada
state: Ontario
city: Windsor
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Bruntal
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: Boulogne-Billancourt
country: France
city: Chambray Les Tours
country: France
city: Echirolles
country: France
city: Montpellier
country: France
city: Orleans
country: France
city: Paris
country: France
city: Rouen
country: France
city: Toulouse
country: France
city: Bad Neuheim
country: Germany
city: Berlin
country: Germany
city: Gommern
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Koeln
country: Germany
city: Olsberg
country: Germany
city: Ratingen
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Eger
country: Hungary
city: Kistarcsa
country: Hungary
city: Nyíregyháza
country: Hungary
city: Szolnok
country: Hungary
city: Székesfehérvár
country: Hungary
city: Veszprem
country: Hungary
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
city: JeonJu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Culiacan
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico City
country: Mexico
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Elblag
country: Poland
city: Nadarzyn
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Almada
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Belgorod
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Chita
country: Russian Federation
city: Kazan
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Khanty-Mansiysk
country: Russian Federation
city: Kursk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Omsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St.Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Zelenograd
country: Russian Federation
city: A Coruna
country: Spain
city: Barcelona
country: Spain
city: Bilbao
country: Spain
city: Córdoba
country: Spain
city: L´Hospitalet de Llobregat
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Sabadell
country: Spain
city: Santiago de Compostela
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Changhua
country: Taiwan
city: Hualien
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Cherkasy
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
city: Ternopil
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Bath
country: United Kingdom
city: Leytonstone
country: United Kingdom
city: London
country: United Kingdom
city: Peterborough
country: United Kingdom
city: Stoke on Trent
country: United Kingdom
city: Upton
country: United Kingdom
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.