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Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS (C-AXSPAND)

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ClinicalTrials.gov Identifier: NCT02552212
Recruitment Status : Active, not recruiting
First Posted : September 17, 2015
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB BIOSCIENCES GmbH )

Tracking Information
First Submitted Date  ICMJE September 15, 2015
First Posted Date  ICMJE September 17, 2015
Last Update Posted Date April 3, 2019
Actual Study Start Date  ICMJE September 2015
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) response criteria response at Week 52 [ Time Frame: Week 52 ]
    This variable is considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it is considered as secondary variable. ASDAS-MI is achieved when there is a reduction (improvement) >= 2.0 in the ASDAS relative to Baseline. The ASDAS is 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 of the C-reactive protein (CRP) [mg/L] + 1) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units).
  • Axial SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 12 [ Time Frame: Week 12 ]
    This variable is 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 is 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) 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 will be measured at Baseline.
  • Certolizumab pegol plasma concentration at Week 1 [ Time Frame: Week 1 ]
    Certolizumab pegol plasma concentration will be measured at Week 1.
  • Certolizumab pegol plasma concentration at Week 2 [ Time Frame: Week 2 ]
    Certolizumab pegol plasma concentration will be measured at Week 2.
  • Certolizumab pegol plasma concentration at Week 4 [ Time Frame: Week 4 ]
    Certolizumab pegol plasma concentration will be measured at Week 4.
  • Certolizumab pegol plasma concentration at Week 12 [ Time Frame: Week 12 ]
    Certolizumab pegol plasma concentration will be measured at Week 12.
  • Certolizumab pegol plasma concentration at Week 24 [ Time Frame: Week 24 ]
    Certolizumab pegol plasma concentration will be measured at Week 24.
  • Certolizumab pegol plasma concentration at Week 36 [ Time Frame: Week 36 ]
    Certolizumab pegol plasma concentration will be measured at Week 36.
  • Certolizumab pegol plasma concentration at Week 52 [ Time Frame: Week 52 ]
    Certolizumab pegol plasma concentration will be measured at Week 52.
  • Certolizumab pegol plasma concentration at Follow-Up (FU) Visit [ Time Frame: Follow-Up Visit (8 weeks after the Week 52) ]
    Certolizumab pegol plasma concentration will be measured at the Follow-Up Visit.
Original Primary Outcome Measures  ICMJE
 (submitted: September 15, 2015)
Percentage of subjects meeting the Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) response criteria at Week 52 [ Time Frame: Week 52 ]
ASDAS-MI is achieved when there is a reduction (improvement) ≥ 2.0 in the ASDAS relative to Baseline. The ASDAS is 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 × PtGADA 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm of the CRP [mg/L] + 1) Back pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units).
Change History Complete list of historical versions of study NCT02552212 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Axial SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 52 [ Time Frame: Week 52 ]
    The ASAS40 response is 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) 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 to Week 12 in the Bath ankylosing spondylitis functional index (BASFI) [ Time Frame: 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 to 10, with lower scores indicating better physical function.
  • Change from Baseline to Week 52 in the Bath ankylosing spondylitis functional index (BASFI) [ Time Frame: From Baseline to Week 52 ]
    The Bath ankylosing spondylitis functional index (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 to 10, with lower scores indicating better physical function.
  • Change from Baseline to Week 12 in the Bath ankylosing spondylitis disease activity index (BASDAI) [ Time Frame: From Baseline to Week 12 ]
    The Bath ankylosing spondylitis disease activity index (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 to 10, with lower scores indicating lower disease activity.
  • Change from Baseline to Week 52 in the Bath ankylosing spondylitis disease activity index (BASDAI) [ Time Frame: From Baseline to Week 52 ]
    The Bath ankylosing spondylitis disease activity index (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 to 10, with lower scores indicating lower disease activity.
  • Change from Baseline to Week 12 in sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) score [ Time Frame: 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.
  • Relevant changes to background medication from Baseline to Week 52 [ Time Frame: From Baseline to Week 52 ]
    The percentage of subjects who do not have relevant changes to background medications during the study treatment period.
  • Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 [ Time Frame: From Baseline to Week 52 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse health-related quality of life (HRQoL).
  • Change from Baseline in ASQoL at Week 1 [ Time Frame: From Baseline to Week 1 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in ASQoL at Week 2 [ Time Frame: From Baseline to Week 2 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in ASQoL at Week 4 [ Time Frame: From Baseline to Week 4 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in ASQoL at Week 12 [ Time Frame: From Baseline to Week 12 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in ASQoL at Week 24 [ Time Frame: From Baseline to Week 24 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in ASQoL at Week 36 [ Time Frame: From Baseline to Week 36 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in ASQoL at Week 48 [ Time Frame: From Baseline to Week 48 ]
    The ASQoL score ranges from 0 to 18 with higher score indicating worse HRQoL.
  • Change from Baseline in nocturnal spinal pain Numerical Rating Scale (NRS) at Week 52 [ Time Frame: From Baseline to Week 52 ]
    The nocturnal pain experienced subjects due to AS will be measured by following question 'How much pain of your spine due to spondylitis do you have at night?'. The NRS will be from 1 to 10 with a higher score indicating worse pain.
  • Occurence of anterior uveitis (AU) or new AU flares through Week 52 [ Time Frame: Throughout the study conduct (up to Week 52) ]
    The percentage of subjects with AU or new AU flares during the study treatment period.
  • Incidence of treatment-emergent adverse events (TEAEs) during the study [ Time Frame: From Baseline until Follow-Up (FU)/Safety Follow-Up Extension (SFE) (up to Week 60/156) ]
    Subjects not participating in the SFE will be assessed at Follow-Up at Week 60. 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.
  • Incidence of serious adverse events (SAEs) during the study [ Time Frame: From Baseline until Follow-Up (FU)/Safety Follow-Up Extension (SFE) (up to Week 60/156) ]
    Subjects not participating in the SFE will be assessed at Follow-Up at Week 60. 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
  • Adverse events leading to withdrawal from investigational medicinal product (IMP) during the study [ Time Frame: From Baseline until Follow-Up (FU)/Safety Follow-Up Extension (SFE) (up to Week 60/156) ]
    Subjects not participating in the SFE will be assessed at Follow-Up at Week 60. 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2015)
  • Percentage of subjects with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) at Week 12 [ Time Frame: Week 12 ]
    The ASAS40 response is 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) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PtGADA), 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.
  • Percentage of subjects with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) at Week 52 [ Time Frame: Week 52 ]
    The ASAS40 response is 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) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PtGADA), 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 to Week 12 in the Bath ankylosing spondylitis functional index (BASFI) [ Time Frame: 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 to 10, with lower scores indicating better physical function.
  • Change from Baseline to Week 52 in the Bath ankylosing spondylitis functional index (BASFI) [ Time Frame: From Baseline to Week 52 ]
    The Bath ankylosing spondylitis functional index (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 to 10, with lower scores indicating better physical function.
  • Change from Baseline to Week 12 in the Bath ankylosing spondylitis disease activity index (BASDAI) [ Time Frame: From Baseline to Week 12 ]
    The Bath ankylosing spondylitis disease activity index (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 to 10, with lower scores indicating lower disease activity.
  • Change from Baseline to Week 52 in the Bath ankylosing spondylitis disease activity index (BASDAI) [ Time Frame: From Baseline to Week 52 ]
    The Bath ankylosing spondylitis disease activity index (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 to 10, with lower scores indicating lower disease activity.
  • Change from Baseline to Week 12 in sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) score [ Time Frame: 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.
  • Percentage of subjects without relevant changes to background medication from Baseline to Week 52 [ Time Frame: From Baseline to Week 52 ]
    The number of subjects who do not have relevant changes to background medications during the study treatment period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Axial Spondyloarthritis
  • Nonradiographic Axial Spondyloarthritis
  • Nr-axSpA
Intervention  ICMJE
  • Biological: Certolizumab Pegol
    • Active Substance: Certolizumab Pegol
    • Pharmaceutical Form: Prefilled syringe
    • Concentration: 200 mg / ml
    • Route of Administration: Subcutaneous injection
    Other Names:
    • Cimzia
    • CDP870
  • Other: Placebo
    • Active Substance: Placebo
    • Pharmaceutical Form: Prefilled syringe
    • Concentration: 0.9 % saline
    • Route of Administration: Subcutaneous injection
Study Arms  ICMJE
  • Experimental: Certolizumab Pegol 200 mg Q2W
    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.
    Intervention: Biological: Certolizumab Pegol
  • Placebo Comparator: Placebo
    Matching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 5, 2017)
317
Original Estimated Enrollment  ICMJE
 (submitted: September 15, 2015)
300
Estimated Study Completion Date  ICMJE April 2020
Actual Primary Completion Date April 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   Czechia,   Hungary,   Poland,   Russian Federation,   Taiwan,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02552212
Other Study ID Numbers  ICMJE AS0006
2015-001894-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UCB Pharma ( UCB BIOSCIENCES GmbH )
Study Sponsor  ICMJE UCB BIOSCIENCES GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: UCB Cares 1-844-599-2273 (UCB)
PRS Account UCB Pharma
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP