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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 : Completed
First Posted : September 17, 2015
Results First Posted : August 17, 2020
Last Update Posted : August 17, 2020
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( 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.

Condition or disease Intervention/treatment Phase
Axial Spondyloarthritis Nonradiographic Axial Spondyloarthritis Nr-axSpA Biological: Certolizumab Pegol Other: Placebo Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 317 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2015
Actual Primary Completion Date : May 2018
Actual Study Completion Date : May 2020


Arm Intervention/treatment
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.
Biological: Certolizumab Pegol
  • Active Substance: Certolizumab Pegol
  • Pharmaceutical Form: Prefilled syringe
  • Concentration: 200 mg / ml
  • Route of Administration: Subcutaneous injection
Other Names:
  • Cimzia
  • CDP870

Placebo Comparator: Placebo
Matching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards.
Other: Placebo
  • Active Substance: Placebo
  • Pharmaceutical Form: Prefilled syringe
  • Concentration: 0.9 % saline
  • Route of Administration: Subcutaneous injection




Primary Outcome Measures :
  1. 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").


  2. 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.


  3. 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).

  4. Certolizumab Pegol Plasma Concentration at Week 1 [ Time Frame: Week 1 ]
    Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.

  5. Certolizumab Pegol Plasma Concentration at Week 2 [ Time Frame: Week 2 ]
    Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.

  6. Certolizumab Pegol Plasma Concentration at Week 4 [ Time Frame: Week 4 ]
    Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.

  7. Certolizumab Pegol Plasma Concentration at Week 12 [ Time Frame: Week 12 ]
    Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.

  8. Certolizumab Pegol Plasma Concentration at Week 24 [ Time Frame: Week 24 ]
    Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.

  9. Certolizumab Pegol Plasma Concentration at Week 36 [ Time Frame: Week 36 ]
    Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.

  10. Certolizumab Pegol Plasma Concentration at Week 52 [ Time Frame: Week 52 ]
    Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.

  11. 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.



Secondary Outcome Measures :
  1. Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52 [ Time Frame: 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.

  2. 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 (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.

  3. Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: 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.

  4. Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: 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.

  5. Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: 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.

  6. 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. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

  7. Number 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 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.


  8. Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 [ Time Frame: 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.

  9. Change From Baseline in ASQoL at Week 1 [ Time Frame: 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.

  10. Change From Baseline in ASQoL at Week 2 [ Time Frame: 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.

  11. Change From Baseline in ASQoL at Week 4 [ Time Frame: 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.

  12. Change From Baseline in ASQoL at Week 12 [ Time Frame: 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.

  13. Change From Baseline in ASQoL at Week 24 [ Time Frame: 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.

  14. Change From Baseline in ASQoL at Week 36 [ Time Frame: 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.

  15. Change From Baseline in ASQoL at Week 48 [ Time Frame: 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.

  16. Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52 [ Time Frame: 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.

  17. Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52 [ Time Frame: Throughout the study conduct (up to Week 52) ]
    The number of subjects with AU or new AU flares during the study treatment period.

  18. Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study [ Time Frame: From Baseline until Week 52 ]
    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.

  19. Percentage of Subjects With Serious Adverse Events (SAEs) During the Study [ Time Frame: From Baseline until Week 52 ]

    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.

  20. Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study [ Time Frame: From Baseline until Week 52 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02552212


Locations
Show Show 105 study locations
Sponsors and Collaborators
UCB BIOSCIENCES GmbH
Investigators
Layout table for investigator information
Study Director: UCB Cares 1-844-599-2273 (UCB)
  Study Documents (Full-Text)

Documents provided by UCB Pharma ( UCB BIOSCIENCES GmbH ):
Study Protocol  [PDF] December 17, 2018
Statistical Analysis Plan  [PDF] March 26, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: UCB BIOSCIENCES GmbH
ClinicalTrials.gov Identifier: NCT02552212    
Other Study ID Numbers: AS0006
2015-001894-41 ( EudraCT Number )
First Posted: September 17, 2015    Key Record Dates
Results First Posted: August 17, 2020
Last Update Posted: August 17, 2020
Last Verified: July 2020
Keywords provided by UCB Pharma ( UCB BIOSCIENCES GmbH ):
Axial Spondyloarthritis
axSpA
Ankylosing Spondylitis
Anti TNF-alpha
Certolizumab Pegol
Nr-axSpA
Non-radiographic
Spondylarthropathies
Arthritis
Spinal Diseases
Immunosuppressive Agents
Additional relevant MeSH terms:
Layout table for MeSH terms
Spondylarthritis
Spondylitis
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Joint Diseases
Arthritis
Certolizumab Pegol
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents