Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS
- Conditions
- Axial SpondyloarthritisNonradiographic Axial SpondyloarthritisNr-axSpA
- Interventions
- Biological: Certolizumab PegolOther: Placebo
- Registration Number
- NCT02552212
- Lead Sponsor
- UCB BIOSCIENCES GmbH
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 317
-
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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Certolizumab Pegol 200 mg Q2W Certolizumab Pegol 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. Placebo Placebo Matching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards.
- Primary Outcome Measures
Name Time Method Certolizumab Pegol Plasma Concentration at Week 12 Week 12 Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Certolizumab Pegol Plasma Concentration at Baseline Baseline (Week 0) Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Certolizumab Pegol Plasma Concentration at Week 1 Week 1 Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 24 Week 24 Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12 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 Week 4 Week 4 Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 52 Week 52 Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit 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.Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52 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").Certolizumab Pegol Plasma Concentration at Week 2 Week 2 Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Certolizumab Pegol Plasma Concentration at Week 36 Week 36 Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
- Secondary Outcome Measures
Name Time Method Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52 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.
Change From Baseline in ASQoL at Week 36 From Baseline to 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.
Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52 Throughout the study conduct (up to Week 52) The number of subjects with AU or new AU flares during the study treatment period.
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI) From Baseline to Week 52 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.
Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52 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.Change From Baseline in ASQoL at Week 2 From Baseline to 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.
Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score From Baseline to Week 12 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.
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 From Baseline to 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.
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI) From Baseline to Week 12 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.
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) From Baseline to Week 12 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.
Change From Baseline in ASQoL at Week 24 From Baseline to 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.
Change From Baseline in ASQoL at Week 4 From Baseline to 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.
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) From Baseline to Week 52 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.
Change From Baseline in ASQoL at Week 1 From Baseline to 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.
Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52 From Baseline to 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.
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) 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.
Change From Baseline in ASQoL at Week 48 From Baseline to 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.
Change From Baseline in ASQoL at Week 12 From Baseline to 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.
Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) 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.
Percentage of Subjects With Serious Adverse Events (SAEs) During the Study From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) 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.
Trial Locations
- Locations (105)
As0006 138
🇺🇸Plantation, Florida, United States
As0006 144
🇺🇸Philadelphia, Pennsylvania, United States
As0006 148
🇺🇸Atlanta, Georgia, United States
As0006 137
🇺🇸Idaho Falls, Idaho, United States
As0006 453
🇷🇺Ivanovo, Russian Federation
As0006 127
🇺🇸Boston, Massachusetts, United States
As0006 104
🇺🇸Seattle, Washington, United States
As0006 110
🇺🇸Eagan, Minnesota, United States
As0006 123
🇺🇸Rochester, Minnesota, United States
As0006 103
🇺🇸Saint Louis, Missouri, United States
As0006 405
🇵🇱Toruń, Poland
As0006 407
🇵🇱Warszawa, Poland
As0006 410
🇵🇱Warszawa, Poland
As0006 450
🇷🇺Kazan, Russian Federation
As0006 125
🇺🇸Birmingham, Alabama, United States
As0006 143
🇺🇸San Francisco, California, United States
As0006 149
🇺🇸Oklahoma City, Oklahoma, United States
As0006 105
🇺🇸Portland, Oregon, United States
As0006 107
🇺🇸Salt Lake City, Utah, United States
As0006 155
🇺🇸Beverly Hills, California, United States
As0006 120
🇺🇸Scottsdale, Arizona, United States
As0006 115
🇺🇸Tucson, Arizona, United States
As0006 117
🇺🇸Daytona Beach, Florida, United States
As0006 101
🇺🇸Palm Desert, California, United States
As0006 116
🇺🇸DeBary, Florida, United States
As0006 160
🇺🇸New Haven, Connecticut, United States
As0006 134
🇺🇸Tampa, Florida, United States
As0006 106
🇺🇸Vero Beach, Florida, United States
As0006 133
🇺🇸New Port Richey, Florida, United States
As0006 102
🇺🇸Cumberland, Maryland, United States
As0006 118
🇺🇸Charlotte, North Carolina, United States
As0006 108
🇺🇸Duncansville, Pennsylvania, United States
As0006 129
🇺🇸Wyomissing, Pennsylvania, United States
As0006 156
🇺🇸Orangeburg, South Carolina, United States
As0006 158
🇺🇸Manitowoc, Wisconsin, United States
As0006 113
🇺🇸Onalaska, Wisconsin, United States
As0006 208
🇦🇺Camperdown, Australia
As0006 210
🇦🇺Coffs Harbour, Australia
As0006 201
🇦🇺Malvern East, Australia
As0006 204
🇦🇺Footscray, Australia
As0006 327
🇨🇿Olomouc, Czechia
As0006 305
🇧🇬Plovdiv, Bulgaria
As0006 304
🇧🇬Ruse, Bulgaria
As0006 205
🇦🇺South Hobart, Australia
As0006 302
🇧🇬Plovdiv, Bulgaria
As0006 209
🇦🇺Maroochydore, Australia
As0006 202
🇦🇺Victoria Park, Australia
As0006 306
🇧🇬Sevlievo, Bulgaria
As0006 300
🇧🇬Sofia, Bulgaria
As0006 307
🇧🇬Sofia, Bulgaria
As0006 309
🇧🇬Sofia, Bulgaria
As0006 308
🇧🇬Varna, Bulgaria
As0006 324
🇨🇿Hustopeče, Czechia
As0006 150
🇨🇦Victoria, Canada
As0006 152
🇨🇦Edmonton, Canada
As0006 326
🇨🇿Hlučín, Czechia
As0006 320
🇨🇿Ostrava, Czechia
As0006 328
🇨🇿Praha 2, Czechia
As0006 323
🇨🇿Praha, Czechia
As0006 322
🇨🇿Pardubice, Czechia
As0006 329
🇨🇿Praha, Czechia
As0006 332
🇨🇿Rychnov Nad Kněžnou, Czechia
As0006 330
🇨🇿Praha, Czechia
As0006 331
🇨🇿Zlín, Czechia
As0006 362
🇭🇺Budapest, Hungary
As0006 333
🇨🇿Příbor, Czechia
As0006 365
🇭🇺Balatonfüred, Hungary
As0006 363
🇭🇺Budapest, Hungary
As0006 400
🇵🇱Elbląg, Poland
As0006 361
🇭🇺Szekesfehervar, Hungary
As0006 406
🇵🇱Bydgoszcz, Poland
As0006 411
🇵🇱Lublin, Poland
As0006 401
🇵🇱Kraków, Poland
As0006 402
🇵🇱Kraków, Poland
As0006 404
🇵🇱Poznań, Poland
As0006 403
🇵🇱Poznań, Poland
As0006 408
🇵🇱Warszawa, Poland
As0006 409
🇵🇱Warszawa, Poland
As0006 413
🇵🇱Wrocław, Poland
As0006 461
🇷🇺Chelyabinsk, Russian Federation
As0006 466
🇷🇺Moscow, Russian Federation
As0006 414
🇵🇱Wrocław, Poland
As0006 451
🇷🇺Kazan, Russian Federation
As0006 455
🇷🇺Moscow, Russian Federation
As0006 458
🇷🇺Kemerovo, Russian Federation
As0006 462
🇷🇺Orenburg, Russian Federation
As0006 452
🇷🇺Ryazan', Russian Federation
As0006 459
🇷🇺Saint Petersburg, Russian Federation
As0006 463
🇷🇺Saint Petersburg, Russian Federation
As0006 464
🇷🇺Saint Petersburg, Russian Federation
As0006 467
🇷🇺Saint Petersburg, Russian Federation
As0006 454
🇷🇺Saratov, Russian Federation
As0006 456
🇷🇺Tolyatti, Russian Federation
As0006 465
🇷🇺Samara, Russian Federation
As0006 460
🇷🇺Smolensk, Russian Federation
As0006 457
🇷🇺Yaroslavl, Russian Federation
As0006 232
🇨🇳Hualien City, Taiwan
As0006 230
🇨🇳Taichung City, Taiwan
As0006 233
🇨🇳Taichung City, Taiwan
As0006 231
🇨🇳Taipei, Taiwan
As0006 124
🇺🇸Fort Lauderdale, Florida, United States
As0006 114
🇺🇸Brooklyn, New York, United States
As0006 147
🇺🇸Worcester, Massachusetts, United States
As0006 141
🇺🇸Cumberland, Maryland, United States
As0006 111
🇺🇸Wheaton, Maryland, United States