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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Axial Spondyloarthritis, Nonradiographic Axial Spondyloarthritis, Nr-axSpA

Intervention / Treatment
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* Biological: Certolizumab Pegol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Certolizumab Pegol 200 mg Q2W<br>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<br>* Active Substance: Certolizumab Pegol Pharmaceutical Form: Prefilled syringe Concentration: 200 mg / ml Route of Administration: Subcutaneous injection<br>* Other names: CDP870;|
| Placebo Comparator: Placebo<br>Matching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards. | Other: Placebo<br>* Active Substance: Placebo Pharmaceutical Form: Prefilled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | Week 12 | 
| Certolizumab Pegol Plasma Concentration at Baseline | Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL). | Baseline (Week 0) | 
| Certolizumab Pegol Plasma Concentration at Week 1 | Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL. | Week 1 | 
| Certolizumab Pegol Plasma Concentration at Week 2 | Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL. | Week 2 | 
| Certolizumab Pegol Plasma Concentration at Week 4 | Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL. | Week 4 | 
| Certolizumab Pegol Plasma Concentration at Week 12 | Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL. | Week 12 | 
| Certolizumab Pegol Plasma Concentration at Week 24 | Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL. | Week 24 | 
| Certolizumab Pegol Plasma Concentration at Week 36 | Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL. | Week 36 | 
| Certolizumab Pegol Plasma Concentration at Week 52 | Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL. | 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. | Follow-up Visit (up to Week 60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Axial Spondyloarthritis, axSpA, Ankylosing Spondylitis, Anti TNF-alpha, Certolizumab Pegol, Nr-axSpA, Non-radiographic, Spondylarthropathies, Arthritis, Spinal Diseases, Immunosuppressive Agents