Clinical trial NCT02505542: Study to Evaluate Maintenance of Sustained Remission of axSpA With CZP Compared to Placebo
Official title: A Multicenter, Open-label (Part A) Followed by a Randomized, Double-blind, Parallel-group, Placebo Controlled Study (Part B) to Evaluate Maintenance of Remission in Subjects With Active Axial Spondyloarthritis (axSpA) Receiving Either Certolizumab Pegol 200 mg Q2W or 200 mg Q4W as Compared to Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial Spondyloarthrithis
Ankylosing Spondylitis
Keywords: Axial Spondyloarthritis
axSpA
Ankylosing Spondylitis
Anti TNF-alpha
Certolizumab Pegol
Remission
Spondylarthropathies
Arthritis
Spinal Diseases
Immunosuppressive Agents
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2015-07-22
Enrollment: 736
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients receive study drug for one year (Part A). If, after the initial run-in phase, a sustained remission is reached they will be randomly split into one of three dose groups for another year (Part B). The maintenance of the sustained remission will be analyzed.


Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) with at least 3 months' symptom duration and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA and symptom duration of less than 5 years prior to the participation of this study
* Active disease at Screening as defined by

  * Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.1
  * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4
  * Spinal pain \> 4 on a 0 to 10 Numerical Rating Scale (NRS) (from BASDAI Item 2)
  * for modified New York (mNY) -negative subjects only: C-reactive Protein (CRP) \> upper limit of normal (ULN) and/or current evidence for sacroiliitis on the Screening Magnetic Resonance Imaging (MRI)
* Inadequate response to, or contraindication to, or intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Exclusion Criteria:

* Presence of total Spinal Ankylosis ('bamboo spine')
* Diagnosis of any other Inflammatory Arthritis
* Prior treatment with any experimental biological agents for treatment of Axial SpondyloArthritis (SpA)
* Exposure to more than 1 TNF-antagonist or primary failure to TNF antagonist therapy
* History of or current chronic or recurrent infections
* High risk of infection
* 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 Participants in Part B Who Did Not Experienced a Flare
timeFrame: From Week 48 to Week 96
Secondary outcomes:
measure: Percentage of Participants Achieving Sustained Remission at Week 48 in Part A
timeFrame: Week 48
measure: Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A
timeFrame: Week 48
measure: Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A
timeFrame: Week 48
measure: Time to Flare in Part B
timeFrame: From Week 48 to Week 96
measure: Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B
timeFrame: Week 96
measure: Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B
timeFrame: Week 96
measure: Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B
timeFrame: Week 96
measure: Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B
timeFrame: Week 96
measure: Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B
timeFrame: Week 96
measure: Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B
timeFrame: Week 96
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B
timeFrame: From Week 48 to Week 96
measure: Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B
timeFrame: From Week 48 to Week 96
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B
timeFrame: From Week 48 to Week 96
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B
timeFrame: From Week 48 to Week 96
measure: Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B
timeFrame: Week 96
measure: Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B
timeFrame: From Week 48 to Week 96
measure: Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B
timeFrame: From Week 48 to Week 96
measure: Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: Escape Week 12
measure: Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: Escape Week 12
measure: Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: Escape Week 12
measure: Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: Escape Week 12
measure: Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: Escape Week 12
measure: Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: Escape Week 12
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: From time of flare to Escape Week 12
measure: Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: From time of flare to Escape Week 12
measure: Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: From time of flare to Escape Week 12
measure: Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: From time of flare to Escape Week 12
measure: Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: From time of flare to Escape Week 12
measure: Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B
timeFrame: From time of flare to Escape Week 12
measure: Certolizumab Pegol (CZP) Plasma Concentration During the Study
timeFrame: From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
measure: Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study
timeFrame: From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
measure: Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study
timeFrame: From Screening Period (Week -5 to Week -1) until Week 48
measure: Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study
timeFrame: From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
measure: Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study
timeFrame: From time of flare to Escape Week 12
Other outcomes:
Locations:
city: Glendale
country: United States
facility: As0005 2313
state: Arizona
city: Mesa
country: United States
facility: As0005 2316
state: Arizona
city: Phoenix
country: United States
facility: As0005 2314
state: Arizona
city: Sun City
country: United States
facility: As0005 2317
state: Arizona
city: Palm Desert
country: United States
facility: As0005 2307
state: California
city: San Francisco
country: United States
facility: As0005 2310
state: California
city: Upland
country: United States
facility: As0005 2305
state: California
city: Denver
country: United States
facility: As0005 2308
state: Colorado
city: Brandon
country: United States
facility: As0005 2302
state: Florida
city: Hagerstown
country: United States
facility: As0005 2321
state: Maryland
city: Minot
country: United States
facility: As0005 2312
state: North Dakota
city: Oklahoma City
country: United States
facility: As0005 2323
state: Oklahoma
city: Duncansville
country: United States
facility: As0005 2311
state: Pennsylvania
city: Jackson
country: United States
facility: As0005 2315
state: Tennessee
city: Austin
country: United States
facility: As0005 2303
state: Texas
city: Dallas
country: United States
facility: As0005 2318
state: Texas
city: Genk
country: Belgium
facility: As0005 1006
city: Gent
country: Belgium
facility: As0005 1001
city: Merksem
country: Belgium
facility: As0005 1004
city: Mons
country: Belgium
facility: As0005 1003
city: Pleven
country: Bulgaria
facility: As0005 1109
city: Plovdiv
country: Bulgaria
facility: As0005 1103
city: Plovdiv
country: Bulgaria
facility: As0005 1106
city: Ruse
country: Bulgaria
facility: As0005 1111
city: Sevlievo
country: Bulgaria
facility: As0005 1110
city: Sofia
country: Bulgaria
facility: As0005 1101
city: Sofia
country: Bulgaria
facility: As0005 1108
city: Brno
country: Czechia
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city: Bruntal
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city: Kladno
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city: Ostrava
country: Czechia
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city: Pardubice
country: Czechia
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city: Praha 11
country: Czechia
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city: Praha 2
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city: Praha 3
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city: Praha 4
country: Czechia
facility: As0005 1302
city: Praha 5
country: Czechia
facility: As0005 1310
city: Praha 5
country: Czechia
facility: As0005 1311
city: Uherske Hradiste
country: Czechia
facility: As0005 1313
city: Zlin
country: Czechia
facility: As0005 1304
city: Montpellier
country: France
facility: As0005 1504
city: Orleans
country: France
facility: As0005 1505
city: Paris
country: France
facility: As0005 1501
city: Tours Cedex 9
country: France
facility: As0005 1503
city: Berlin
country: Germany
facility: As0005 1406
city: Berlin
country: Germany
facility: As0005 1408
city: Berlin
country: Germany
facility: As0005 1410
city: Berlin
country: Germany
facility: As0005 1412
city: Bochum
country: Germany
facility: As0005 1413
city: Erlangen
country: Germany
facility: As0005 1405
city: Frankfurt am Main
country: Germany
facility: As0005 1404
city: Hamburg
country: Germany
facility: As0005 1402
city: Herne
country: Germany
facility: As0006 1409
city: Koeln
country: Germany
facility: As0005 1407
city: Leipzig
country: Germany
facility: As0005 1403
city: Budapest
country: Hungary
facility: As0005 1705
city: Budapest
country: Hungary
facility: As0005 1710
city: Debrecen
country: Hungary
facility: As0005 1704
city: Miskolc
country: Hungary
facility: As0005 1706
city: Nyiregyhaza
country: Hungary
facility: As0005 1711
city: Szeged
country: Hungary
facility: As0005 1707
city: Szentes
country: Hungary
facility: As0005 1702
city: Szombathely
country: Hungary
facility: As0005 1703
city: Veszprem
country: Hungary
facility: As0005 1701
city: Amsterdam
country: Netherlands
facility: As0005 2502
city: Rotterdam
country: Netherlands
facility: As0005 2503
city: Sneek
country: Netherlands
facility: As0005 2501
city: Bialystok
country: Poland
facility: As0005 1806
city: Bydgoszcz
country: Poland
facility: As0005 1805
city: Elblag
country: Poland
facility: As0005 1801
city: Elblag
country: Poland
facility: As0005 1802
city: Krakow
country: Poland
facility: As0005 1812
city: Lodz
country: Poland
facility: As0005 1808
city: Lodz
country: Poland
facility: As0005 1814
city: Lublin
country: Poland
facility: As0005 1803
city: Ostrowiec Swietokrzyski
country: Poland
facility: As0005 1816
city: Poznan
country: Poland
facility: As0005 1809
city: Poznan
country: Poland
facility: As0005 1813
city: Torun
country: Poland
facility: As0005 1807
city: Warszawa
country: Poland
facility: As0005 1804
city: Warszawa
country: Poland
facility: As0005 1811
city: Warszawa
country: Poland
facility: As0005 1815
city: Braila
country: Romania
facility: As0005 1904
city: Brasov
country: Romania
facility: As0005 1912
city: Bucuresti
country: Romania
facility: As0005 1902
city: Bucuresti
country: Romania
facility: As0005 1903
city: Bucuresti
country: Romania
facility: As0005 1913
city: Cluj-Napoca
country: Romania
facility: As0005 1907
city: Iasi
country: Romania
facility: As0005 1910
city: Târgu-Mureş
country: Romania
facility: As0005 1911
city: Cordoba
country: Spain
facility: As0005 2403
city: Getafe
country: Spain
facility: As0005 2404
city: Madrid
country: Spain
facility: As0005 2401
city: Sevilla
country: Spain
facility: As0005 2402
city: Kaohsiung
country: Taiwan
facility: As0005 2205
city: Taichung
country: Taiwan
facility: As0005 2201
city: Taichung
country: Taiwan
facility: As0005 2202
city: Taipei
country: Taiwan
facility: As0005 2203
city: Taipei
country: Taiwan
facility: As0005 2204
city: Taipei
country: Taiwan
facility: As0005 2206
city: Ankara
country: Turkey
facility: As0005 2101
city: Edirne
country: Turkey
facility: As0005 2103
city: Gaziantep
country: Turkey
facility: As0005 2102
city: Istanbul
country: Turkey
facility: As0005 2105
city: Istanbul
country: Turkey
facility: As0005 2106
city: Izmir
country: Turkey
facility: As0005 2104
city: Leeds
country: United Kingdom
facility: As0005 1603
city: Norwich
country: United Kingdom
facility: As0005 1601
Study officials:
affiliation: +1 844 599 2273(UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: Landewe RB, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch FE, Gaffney K, Bauer L, Hoepken B, Davies OR, de Peyrecave N, Thomas K, Gensler LS. Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Ann Rheum Dis. 2020 Jul;79(7):920-928. doi: 10.1136/annrheumdis-2019-216839. Epub 2020 May 7.
citation: Landewe R, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch F, Gaffney K, Bauer L, Hoepken B, de Peyrecave N, Thomas K, Gensler LS. Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE. Rheumatol Ther. 2020 Sep;7(3):581-599. doi: 10.1007/s40744-020-00214-7. Epub 2020 Jun 11.