Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis

Study Overview
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Brief Summary
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The study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of two dose regimens of Certolizumab Pegol (CZP) in subjects with active axial Spondyloarthritis (axial SpA).

Official Title
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Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis

Conditions
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Spondyloarthropathies

Intervention / Treatment
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* Biological: CZP 200 mg Q2W
* Biological: CZP 400 mg Q4W
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of adult-onset axial Spondyloarthritis (SpA) of at least 3 months' duration as defined by the specified Assessment of Spondyloarthritis International Society (ASAS) criteria Active disease as defined by: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 Back pain ≥ 4 on a 0 to 10 Neurobehavioral Rating Scale (NRS) (from BASDAI item 2) C-Reactive Protein (CRP) > ULN (Upper Limit of Normal) and/or current evidence (ie, within the last 3 months from Screening) for Sacroiliitis on Magnetic Resonance Imaging (MRI) as defined by Assessment of Spondyloarthritis International Society (ASAS) criteria Intolerance to or inadequate response to at least 1 Nonsteroidal Anti-Inflammatory Drug (NSAID) Exclusion Criteria: Presence of total Spinal Ankylosis (bamboo spine) Diagnosis of any other Inflammatory Arthritis Prior treatment with any experimental biological agents for treatment of Axial Spondyloarthritis (SpA) Exposure to more than 1 TNF-antagonist or to more than 2 previous biological agents for Axial Spondyloarthritis (SpA) History of or current chronic or recurrent infections High risk of infection 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CZP 200 mg Q2W<br>Subjects received 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. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. | Biological: CZP 200 mg Q2W<br>* 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Experimental: CZP 400 mg Q4W<br>Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind. | Biological: CZP 400 mg Q4W<br>* 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Placebo Comparator: Placebo<br>Matching Placebo to CZP injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg Q2W or CZP 400 mg Q4W. | Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 200 mg escape on Week 16<br>Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 22 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind. | Biological: CZP 200 mg Q2W<br>* 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 400 mg escape on Week 16<br>Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 24 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind. | Biological: CZP 400 mg Q4W<br>* 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 200 mg on Week 24<br>Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 30 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind. | Biological: CZP 200 mg Q2W<br>* 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|
| Other: Placebo to CZP 400 mg on Week 24<br>Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 32 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind. | Biological: CZP 400 mg Q4W<br>* 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).<br>* Other names: Certolizumab Pegol;Other: Placebo<br>* Matching Placebo to CZP injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 12 | The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains: Patient's Global Assessment of Disease Activity Pain assessment (total spinal pain) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 24 | The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains: Patient's Global Assessment of Disease Activity Pain assessment (total spinal pain) Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit). | Week 24 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12 | The BASFI assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 (Easy) to 10 (Impossible). 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. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline to Week 12 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 | The BASFI assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 (Easy) to 10 (Impossible). 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. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline to Week 24 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 12 | The BASDAI is a validated self-reported instrument which consists of six 10 unit horizontal Numerical Rating Scales (NRSs) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity. A negative value in BASDAI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline to Week 12 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 | The BASDAI is a validated self-reported instrument which consists of six 10 unit horizontal Numerical Rating Scales (NRSs) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity. A negative value in BASDAI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline to Week 24 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12 | The BASMI characterizes the spinal mobility of subjects with axial Spondyloarthritis (SpA) and Ankylosing Spondylitis (AS). It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline to Week 12 | 
| Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 24 | The BASMI characterizes the spinal mobility of subjects with axial SpA and AS. It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement. | From Baseline to Week 24 | 
| Change From Baseline in the Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging (MRI) Scoring System for Disease Activity (ASspiMRI-a) in the Berlin Modification at Week 12 | The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. A VU is defined as the region between 2 virtual lines through the middle of each vertebra. Active inflammation is scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. Total spine ASspiMRI-a score in the Berlin modification can range from 0 to 69 with higher scores indicating higher disease activity. A negative value in total spine ASspiMRI-a score change from Baseline indicates an improvement from Baseline. The higher the negative value the higher the reduction of inflammation. | From Baseline to Week 12 | 
| Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 12 | The 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. A negative value in SPARCC change from Baseline indicates an improvement from Baseline. The higher the negative value the higher the reduction of inflammation. | From Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Certolizumab Pegol, Cimzia