Axial SpondyloarthritisPhase 3C-AXSPANDNCT02552212
Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS
A Phase 3 study testing Certolizumab Pegol in people with Axial Spondyloarthritis and Nonradiographic Axial Spondyloarthritis, run by UCB BIOSCIENCES GmbH at 105 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Axial Spondyloarthritis, Nonradiographic Axial Spondyloarthritis, Nr-axSpA
- What is being tested?
- Certolizumab Pegol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 317 participants
- Where
- 105 sitesin 9 countries
- Study dates
- Sep 2015to May 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
105 sites in 9 countries.
105 sites in 9 countries
United States36 sites
As0006 148
Atlanta, Georgia
As0006 155
Beverly Hills, California
As0006 125
Birmingham, Alabama
As0006 127
Boston, Massachusetts
As0006 114
Brooklyn, New York
As0006 118
Charlotte, North Carolina
As0006 102
Cumberland, Maryland
As0006 141
Cumberland, Maryland
As0006 117
Daytona Beach, Florida
As0006 116
DeBary, Florida
As0006 108
Duncansville, Pennsylvania
As0006 110
Eagan, Minnesota
As0006 124
Fort Lauderdale, Florida
As0006 137
Idaho Falls, Idaho
As0006 158
Manitowoc, Wisconsin
As0006 160
New Haven, Connecticut
As0006 133
New Port Richey, Florida
As0006 149
Oklahoma City, Oklahoma
As0006 113
Onalaska, Wisconsin
As0006 156
Orangeburg, South Carolina
As0006 101
Palm Desert, California
As0006 144
Philadelphia, Pennsylvania
As0006 138
Plantation, Florida
As0006 105
Portland, Oregon
As0006 123
Rochester, Minnesota
As0006 107
Salt Lake City, Utah
As0006 143
San Francisco, California
As0006 120
Scottsdale, Arizona
As0006 104
Seattle, Washington
As0006 103
St Louis, Missouri
As0006 134
Tampa, Florida
As0006 115
Tucson, Arizona
As0006 106
Vero Beach, Florida
As0006 111
Wheaton, Maryland
As0006 147
Worcester, Massachusetts
As0006 129
Wyomissing, Pennsylvania
Russia18 sites
As0006 461
Chelyabinsk
As0006 453
Ivanovo
As0006 450
Kazan'
As0006 451
Kazan'
As0006 458
Kemerovo
As0006 455
Moscow
As0006 466
Moscow
As0006 462
Orenburg
As0006 452
Ryazan
As0006 459
Saint Petersburg
As0006 463
Saint Petersburg
As0006 464
Saint Petersburg
As0006 467
Saint Petersburg
As0006 465
Samara
As0006 454
Saratov
As0006 460
Smolensk
As0006 456
Tolyatti
As0006 457
Yaroslavl
Poland14 sites
As0006 406
Bydgoszcz
As0006 400
Elblag
As0006 401
Krakow
As0006 402
Krakow
As0006 411
Lublin
As0006 403
Poznan
As0006 404
Poznan
As0006 405
Torun
As0006 407
Warsaw
As0006 408
Warsaw
As0006 409
Warsaw
As0006 410
Warsaw
As0006 413
Wroclaw
As0006 414
Wroclaw
Czechia12 sites
As0006 326
Hlučín
As0006 324
Hustopeče
As0006 327
Olomouc
As0006 320
Ostrava
As0006 322
Pardubice
As0006 323
Prague
As0006 328
Prague
As0006 329
Prague
As0006 330
Prague
As0006 333
Příbor
As0006 332
Rychnov nad Kněžnou
As0006 331
Zlín
Bulgaria8 sites
As0006 302
Plovdiv
As0006 305
Plovdiv
As0006 304
Rousse
As0006 306
Sevlievo
As0006 300
Sofia
As0006 307
Sofia
As0006 309
Sofia
As0006 308
Varna
Australia7 sites
As0006 208
Camperdown
As0006 210
Coffs Harbour
As0006 204
Footscray
As0006 201
Malvern East
As0006 209
Maroochydore
As0006 205
South Hobart
As0006 202
Victoria Park
Hungary4 sites
As0006 365
Balatonfüred
As0006 362
Budapest
As0006 363
Budapest
As0006 361
Székesfehérvár
Taiwan4 sites
As0006 232
Hualien City
As0006 230
Taichung
As0006 233
Taichung
As0006 231
Taipei
About this study
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
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.
- Being tested
- Certolizumab Pegol, Placebo
- Keywords
- Axial Spondyloarthritis, axSpA, Ankylosing Spondylitis, Anti TNF-alpha, Certolizumab Pegol, Nr-axSpA, Non-radiographic, Spondylarthropathies, Arthritis, Spinal Diseases, Immunosuppressive Agents
- Medical subject headings
- Axial Spondyloarthritis, Non-Radiographic Axial Spondyloarthritis, Spondylitis, Ankylosing, Spondylarthropathies, Arthritis, Spinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Certolizumab PegolBiological
Also called Cimzia, CDP870
- Active Substance: Certolizumab Pegol
- Pharmaceutical Form: Prefilled syringe
- Concentration: 200 mg / ml
- Route of Administration: Subcutaneous injection
PlaceboOther
- Active Substance: Placebo
- Pharmaceutical Form: Prefilled syringe
- Concentration: 0.9 % saline
- Route of Administration: Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Certolizumab Pegol 200 mg Q2W | Experimental | Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. Receives: Biological: Certolizumab Pegol |
| Placebo | Placebo comparator | Matching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable.
ASDAS-MI was achieved when there was a reduction (improvement) >= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached.
The ASDAS was calculated as the sum of the following components:
0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is "not active" and 10 is "very active").
Measured: Week 52
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries.
The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Measured: Week 12
Certolizumab Pegol Plasma Concentration at Baseline
Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Measured: Baseline (Week 0)
Certolizumab Pegol Plasma Concentration at Week 1
Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Measured: Week 1
Certolizumab Pegol Plasma Concentration at Week 2
Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Measured: Week 2
Certolizumab Pegol Plasma Concentration at Week 4
Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Measured: Week 4
Certolizumab Pegol Plasma Concentration at Week 12
Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Measured: Week 12
Certolizumab Pegol Plasma Concentration at Week 24
Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Measured: Week 24
Certolizumab Pegol Plasma Concentration at Week 36
Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
Measured: Week 36
Certolizumab Pegol Plasma Concentration at Week 52
Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Measured: Week 52
Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL.
Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period.
Measured: Follow-up Visit (up to Week 60)
Secondary outcomes (20)
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52
The ASAS40 response was defined as relative improvements of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Measured: Week 52
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 12
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 52
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 12
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 52
Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score
The Spondyloarthritis Research Consortium of Canada (SPARCC) scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 12
Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52
The number of subjects who did not have relevant changes to background medications during the study treatment period.
A subject is without relevant changes to background medication if they do not have: the addition of a new disease-modifying antirheumatic drug (DMARD) or the change from one DMAR to another; the addition of an nonsteroidal anti-inflammatory drug (NSAID) or the change from one NSAID to another; an increased dose of chronic corticosteroids; the addition of a new chronic analgesic medication or increased dose in chronic analgesic medication; and they complete double-blind study treatment to Week 52.
Measured: From Baseline to Week 52
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 52
Change From Baseline in ASQoL at Week 1
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 1
Change From Baseline in ASQoL at Week 2
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 2
Change From Baseline in ASQoL at Week 4
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 4
Change From Baseline in ASQoL at Week 12
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 12
Change From Baseline in ASQoL at Week 24
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 24
Change From Baseline in ASQoL at Week 36
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 36
Change From Baseline in ASQoL at Week 48
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 48
Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52
The nocturnal spinal pain experienced by subjects due to AS was measured by following question 'How much pain of your spine due to spondylitis do you have at night?'. The NRS ranged from 0 to 10, where 0 represented 'no pain' and 10 represented 'most severe pain'. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Measured: From Baseline to Week 52
Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52
The number of subjects with AU or new AU flares during the study treatment period.
Measured: Throughout the study conduct (up to Week 52)
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Measured: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Percentage of Subjects With Serious Adverse Events (SAEs) During the Study
A serious adverse event (SAE) is any untoward medical occurrence that at any dose:
- Results in death
- Is life-threatening
- Requires in patient hospitalization or prolongation of existing hospitalization
- Is a congenital anomaly or birth defect
- Is an infection that requires treatment parenteral antibiotics
- Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Measured: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Measured: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2015 (estimated)
- Study startSep 2015
- Primary completionMay 2018
- Study completionMay 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Axial SpondyloarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 317 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB BIOSCIENCES GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Cares, Study director, 1-844-599-2273 (UCB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02552212
- Sponsor's protocol ID
- AS0006
- Other IDs
- 2015-001894-41, 2015
- Acronym
- C-AXSPAND
- Status last verified
- Aug 2022
- First submitted
- 15 Sep 2015
- Last updated
- 18 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
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.
PubMed 35296532Robinson 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.
PubMed 35733363Maksymowych 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.
PubMed 34715908Deodhar 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.
PubMed 30848558
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02552212
- Acronym / sponsor ID
- C-AXSPAND / AS0006
- Keywords
- Axial Spondyloarthritis, axSpA, Ankylosing Spondylitis, Anti TNF-alpha, Certolizumab Pegol, Nr-axSpA, Non-radiographic, Spondylarthropathies
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 317 participants (actual)
- Lead sponsor
- UCB BIOSCIENCES GmbHIndustry (pharma, biotech, devices)
- Study start
- Sep 2015 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2020 (actual)
- First posted
- 17 Sep 2015 (estimated)
- Results
- Posted 17 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Certolizumab Pegol 200 mg Q2W | Experimental | Biological: Certolizumab PegolCertolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. |
| Placebo | Placebo comparator | Other: PlaceboMatching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Certolizumab PegolAlso: Cimzia, CDP870* Active Substance: Certolizumab Pegol * Pharmaceutical Form: Prefilled syringe * Concentration: 200 mg / ml * Route of Administration: Subcutaneous injection | Biological | Certolizumab Pegol 200 mg Q2W |
| Placebo* Active Substance: Placebo * Pharmaceutical Form: Prefilled syringe * Concentration: 0.9 % saline * Route of Administration: Subcutaneous injection | Other | Placebo |
Primary outcome
Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
Time frame: Week 52
This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable. ASDAS-MI was achieved when there was a reduction (improvement) >= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached. The ASDAS was calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is "not active" and 10 is "very active").
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
Time frame: Week 12
This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries. The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Certolizumab Pegol Plasma Concentration at Baseline
Time frame: Baseline (Week 0)
Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Certolizumab Pegol Plasma Concentration at Week 1
Time frame: Week 1
Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 2
Time frame: Week 2
Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 4
Time frame: Week 4
Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 12
Time frame: Week 12
Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 24
Time frame: Week 24
Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 36
Time frame: Week 36
Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 52
Time frame: Week 52
Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
Time frame: Follow-up Visit (up to Week 60)
Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL. Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period.
20 secondary outcomes
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52
Time frame: Week 52
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
Time frame: From Baseline to Week 12
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
Time frame: From Baseline to Week 52
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Time frame: From Baseline to Week 12
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Time frame: From Baseline to Week 52
Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score
Time frame: From Baseline to Week 12
Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52
Time frame: From Baseline to Week 52
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
Time frame: From Baseline to Week 52
Change From Baseline in ASQoL at Week 1
Time frame: From Baseline to Week 1
Change From Baseline in ASQoL at Week 2
Time frame: From Baseline to Week 2
Change From Baseline in ASQoL at Week 4
Time frame: From Baseline to Week 4
Change From Baseline in ASQoL at Week 12
Time frame: From Baseline to Week 12
Change From Baseline in ASQoL at Week 24
Time frame: From Baseline to Week 24
Change From Baseline in ASQoL at Week 36
Time frame: From Baseline to Week 36
Change From Baseline in ASQoL at Week 48
Time frame: From Baseline to Week 48
Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52
Time frame: From Baseline to Week 52
Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52
Time frame: Throughout the study conduct (up to Week 52)
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study
Time frame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Percentage of Subjects With Serious Adverse Events (SAEs) During the Study
Time frame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study
Time frame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35296532van 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.
- Results publication: PubMed 35733363Robinson 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.
- Derived from this study: PubMed 34715908Maksymowych 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.
- Derived from this study: PubMed 30848558Deodhar 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.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Cares study director
1-844-599-2273 (UCB)
105 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Certolizumab Pegol in people with Axial Spondyloarthritis and Nonradiographic Axial Spondyloarthritis, run by UCB BIOSCIENCES GmbH at 105 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 105 sites in United States, Russia, Poland, Czechia, Bulgaria and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52 (time frame: Week 52). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02552212, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2022.