Clinical trial NCT02552212: Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS
Official title: Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis (axSpA) Without X-Ray Evidence of Ankylosing Spondylitis (AS) and Objective Signs of Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Nonradiographic Axial Spondyloarthritis
Nr-axSpA
Keywords: Axial Spondyloarthritis
axSpA
Ankylosing Spondylitis
Anti TNF-alpha
Certolizumab Pegol
Nr-axSpA
Non-radiographic
Spondylarthropathies
Arthritis
Spinal Diseases
Immunosuppressive Agents
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2015-09-17
Enrollment: 317
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: Patients with active Axial Spondyloarthritis without x-ray evidence of Ankylosing Spondylitis and with signs of inflammation will be randomly assigned to receive certolizumab pegol (CZP) 200 mg every two weeks or placebo. The primary objective is to demonstrate the efficacy of CZP in these patients.


Eligibility criteria: Inclusion Criteria:

* At least 18 years old at the start of Screening Visit
* A documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA
* Subjects must have had back pain for at least 12 months before Screening
* No sacroiliitis defined by Modified New York (mNY) criteria on sacroiliac (SI) x-rays
* Active disease at Screening as defined by

  * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score \>= 4
  * Spinal pain \>= 4 on a 0 to 10 Numerical Rating Scale (NRS)
* Inadequate response to, have a contraindication to, or have been intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Exclusion Criteria:

* Diagnosis of AS or any other Inflammatory Arthritis
* Prior treatment with any experimental biological agents for treatment of Axial SpondyloArthritis (SpA)
* Exposure to more than 1 tumor necrosis factor (TNF)-antagonist or primary failure to TNF antagonist therapy
* History of or current chronic or recurrent infections
* Subjects with known Tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent Tuberculosis (LTB)
* Recent live vaccination
* Concurrent malignancy or a history of malignancy
* Class III or IV congestive heart failure - New York Heart Association (NYHA)
* Demyelinating disease of the central nervous system
* Female subjects who are breastfeeding, pregnant or plan to become pregnant during the study or within 3 months following the last dose of the investigational product
* Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion in the study

Primary outcomes:
measure: Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
timeFrame: Week 52
measure: Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
timeFrame: Week 12
measure: Certolizumab Pegol Plasma Concentration at Baseline
timeFrame: Baseline (Week 0)
measure: Certolizumab Pegol Plasma Concentration at Week 1
timeFrame: Week 1
measure: Certolizumab Pegol Plasma Concentration at Week 2
timeFrame: Week 2
measure: Certolizumab Pegol Plasma Concentration at Week 4
timeFrame: Week 4
measure: Certolizumab Pegol Plasma Concentration at Week 12
timeFrame: Week 12
measure: Certolizumab Pegol Plasma Concentration at Week 24
timeFrame: Week 24
measure: Certolizumab Pegol Plasma Concentration at Week 36
timeFrame: Week 36
measure: Certolizumab Pegol Plasma Concentration at Week 52
timeFrame: Week 52
measure: Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
timeFrame: Follow-up Visit (up to Week 60)
Secondary outcomes:
measure: Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52
timeFrame: Week 52
measure: Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: From Baseline to Week 12
measure: Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: From Baseline to Week 52
measure: Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: From Baseline to Week 12
measure: Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: From Baseline to Week 52
measure: Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score
timeFrame: From Baseline to Week 12
measure: Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52
timeFrame: From Baseline to Week 52
measure: Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
timeFrame: From Baseline to Week 52
measure: Change From Baseline in ASQoL at Week 1
timeFrame: From Baseline to Week 1
measure: Change From Baseline in ASQoL at Week 2
timeFrame: From Baseline to Week 2
measure: Change From Baseline in ASQoL at Week 4
timeFrame: From Baseline to Week 4
measure: Change From Baseline in ASQoL at Week 12
timeFrame: From Baseline to Week 12
measure: Change From Baseline in ASQoL at Week 24
timeFrame: From Baseline to Week 24
measure: Change From Baseline in ASQoL at Week 36
timeFrame: From Baseline to Week 36
measure: Change From Baseline in ASQoL at Week 48
timeFrame: From Baseline to Week 48
measure: Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52
timeFrame: From Baseline to Week 52
measure: Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52
timeFrame: Throughout the study conduct (up to Week 52)
measure: Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study
timeFrame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
measure: Percentage of Subjects With Serious Adverse Events (SAEs) During the Study
timeFrame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
measure: Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study
timeFrame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: As0006 125
state: Alabama
city: Scottsdale
country: United States
facility: As0006 120
state: Arizona
city: Tucson
country: United States
facility: As0006 115
state: Arizona
city: Beverly Hills
country: United States
facility: As0006 155
state: California
city: Palm Desert
country: United States
facility: As0006 101
state: California
city: San Francisco
country: United States
facility: As0006 143
state: California
city: New Haven
country: United States
facility: As0006 160
state: Connecticut
city: Daytona Beach
country: United States
facility: As0006 117
state: Florida
city: DeBary
country: United States
facility: As0006 116
state: Florida
city: Fort Lauderdale
country: United States
facility: As0006 124
state: Florida
city: New Port Richey
country: United States
facility: As0006 133
state: Florida
city: Plantation
country: United States
facility: As0006 138
state: Florida
city: Tampa
country: United States
facility: As0006 134
state: Florida
city: Vero Beach
country: United States
facility: As0006 106
state: Florida
city: Atlanta
country: United States
facility: As0006 148
state: Georgia
city: Idaho Falls
country: United States
facility: As0006 137
state: Idaho
city: Cumberland
country: United States
facility: As0006 102
state: Maryland
city: Cumberland
country: United States
facility: As0006 141
state: Maryland
city: Wheaton
country: United States
facility: As0006 111
state: Maryland
city: Boston
country: United States
facility: As0006 127
state: Massachusetts
city: Worcester
country: United States
facility: As0006 147
state: Massachusetts
city: Eagan
country: United States
facility: As0006 110
state: Minnesota
city: Rochester
country: United States
facility: As0006 123
state: Minnesota
city: Saint Louis
country: United States
facility: As0006 103
state: Missouri
city: Brooklyn
country: United States
facility: As0006 114
state: New York
city: Charlotte
country: United States
facility: As0006 118
state: North Carolina
city: Oklahoma City
country: United States
facility: As0006 149
state: Oklahoma
city: Portland
country: United States
facility: As0006 105
state: Oregon
city: Duncansville
country: United States
facility: As0006 108
state: Pennsylvania
city: Philadelphia
country: United States
facility: As0006 144
state: Pennsylvania
city: Wyomissing
country: United States
facility: As0006 129
state: Pennsylvania
city: Orangeburg
country: United States
facility: As0006 156
state: South Carolina
city: Salt Lake City
country: United States
facility: As0006 107
state: Utah
city: Seattle
country: United States
facility: As0006 104
state: Washington
city: Manitowoc
country: United States
facility: As0006 158
state: Wisconsin
city: Onalaska
country: United States
facility: As0006 113
state: Wisconsin
city: Camperdown
country: Australia
facility: As0006 208
city: Coffs Harbour
country: Australia
facility: As0006 210
city: Footscray
country: Australia
facility: As0006 204
city: Malvern East
country: Australia
facility: As0006 201
city: Maroochydore
country: Australia
facility: As0006 209
city: South Hobart
country: Australia
facility: As0006 205
city: Victoria Park
country: Australia
facility: As0006 202
city: Plovdiv
country: Bulgaria
facility: As0006 302
city: Plovdiv
country: Bulgaria
facility: As0006 305
city: Ruse
country: Bulgaria
facility: As0006 304
city: Sevlievo
country: Bulgaria
facility: As0006 306
city: Sofia
country: Bulgaria
facility: As0006 300
city: Sofia
country: Bulgaria
facility: As0006 307
city: Sofia
country: Bulgaria
facility: As0006 309
city: Varna
country: Bulgaria
facility: As0006 308
city: Edmonton
country: Canada
facility: As0006 152
city: Victoria
country: Canada
facility: As0006 150
city: Hlučín
country: Czechia
facility: As0006 326
city: Hustopeče
country: Czechia
facility: As0006 324
city: Olomouc
country: Czechia
facility: As0006 327
city: Ostrava
country: Czechia
facility: As0006 320
city: Pardubice
country: Czechia
facility: As0006 322
city: Praha 2
country: Czechia
facility: As0006 328
city: Praha
country: Czechia
facility: As0006 323
city: Praha
country: Czechia
facility: As0006 329
city: Praha
country: Czechia
facility: As0006 330
city: Příbor
country: Czechia
facility: As0006 333
city: Rychnov Nad Kněžnou
country: Czechia
facility: As0006 332
city: Zlín
country: Czechia
facility: As0006 331
city: Balatonfüred
country: Hungary
facility: As0006 365
city: Budapest
country: Hungary
facility: As0006 362
city: Budapest
country: Hungary
facility: As0006 363
city: Szekesfehervar
country: Hungary
facility: As0006 361
city: Bydgoszcz
country: Poland
facility: As0006 406
city: Elbląg
country: Poland
facility: As0006 400
city: Kraków
country: Poland
facility: As0006 401
city: Kraków
country: Poland
facility: As0006 402
city: Lublin
country: Poland
facility: As0006 411
city: Poznań
country: Poland
facility: As0006 403
city: Poznań
country: Poland
facility: As0006 404
city: Toruń
country: Poland
facility: As0006 405
city: Warszawa
country: Poland
facility: As0006 407
city: Warszawa
country: Poland
facility: As0006 408
city: Warszawa
country: Poland
facility: As0006 409
city: Warszawa
country: Poland
facility: As0006 410
city: Wrocław
country: Poland
facility: As0006 413
city: Wrocław
country: Poland
facility: As0006 414
city: Chelyabinsk
country: Russian Federation
facility: As0006 461
city: Ivanovo
country: Russian Federation
facility: As0006 453
city: Kazan
country: Russian Federation
facility: As0006 450
city: Kazan
country: Russian Federation
facility: As0006 451
city: Kemerovo
country: Russian Federation
facility: As0006 458
city: Moscow
country: Russian Federation
facility: As0006 455
city: Moscow
country: Russian Federation
facility: As0006 466
city: Orenburg
country: Russian Federation
facility: As0006 462
city: Ryazan'
country: Russian Federation
facility: As0006 452
city: Saint Petersburg
country: Russian Federation
facility: As0006 459
city: Saint Petersburg
country: Russian Federation
facility: As0006 463
city: Saint Petersburg
country: Russian Federation
facility: As0006 464
city: Saint Petersburg
country: Russian Federation
facility: As0006 467
city: Samara
country: Russian Federation
facility: As0006 465
city: Saratov
country: Russian Federation
facility: As0006 454
city: Smolensk
country: Russian Federation
facility: As0006 460
city: Tolyatti
country: Russian Federation
facility: As0006 456
city: Yaroslavl
country: Russian Federation
facility: As0006 457
city: Hualien City
country: Taiwan
facility: As0006 232
city: Taichung City
country: Taiwan
facility: As0006 230
city: Taichung City
country: Taiwan
facility: As0006 233
city: Taipei
country: Taiwan
facility: As0006 231
Study officials:
affiliation: 1-844-599-2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: van der Heijde D, Gensler LS, Maksymowych WP, Landewe R, Rudwaleit M, Bauer L, Kumke T, Kim M, Auteri SE, Hoepken B, Deodhar A. Long-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study. RMD Open. 2022 Mar;8(1):e002138. doi: 10.1136/rmdopen-2021-002138.
citation: Robinson PC, Maksymowych WP, Gensler LS, Hall S, Rudwaleit M, Hoepken B, Bauer L, Kumke T, Kim M, de Peyrecave N, Deodhar A. Certolizumab Pegol Efficacy in Patients With Non-Radiographic Axial Spondyloarthritis Stratified by Baseline MRI and C-Reactive Protein Status: An Analysis From the C-axSpAnd Study. ACR Open Rheumatol. 2022 Sep;4(9):794-801. doi: 10.1002/acr2.11469. Epub 2022 Jun 22.
citation: Maksymowych WP, Kumke T, Auteri SE, Hoepken B, Bauer L, Rudwaleit M. Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol. Arthritis Res Ther. 2021 Oct 29;23(1):274. doi: 10.1186/s13075-021-02650-4.
citation: Deodhar A, Gensler LS, Kay J, Maksymowych WP, Haroon N, Landewe R, Rudwaleit M, Hall S, Bauer L, Hoepken B, de Peyrecave N, Kilgallen B, van der Heijde D. A Fifty-Two-Week, Randomized, Placebo-Controlled Trial of Certolizumab Pegol in Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Jul;71(7):1101-1111. doi: 10.1002/art.40866. Epub 2019 May 28.