Ankylosing Spondylitis, Axial Spondyloarthrithis
Conditions
Keywords
Axial Spondyloarthritis, axSpA, Ankylosing Spondylitis, Anti TNF-alpha, Certolizumab Pegol, Remission, Spondylarthropathies, Arthritis, Spinal Diseases, Immunosuppressive Agents
Brief summary
Patients receive study drug for one year (Part A). If, after the initial run-in phase, a sustained remission is reached they will be randomly split into one of three dose groups for another year (Part B). The maintenance of the sustained remission will be analyzed.
Interventions
BIOLOGICALCertolizumab Pegol
* Active substance: Certolizumab Pegol * Pharmaceutical form: Prefilled syringe * Concentration: 200 mg / ml * Route of Administration: Subcutaneous injection
OTHERPlacebo
* Active substance: Placebo * Pharmaceutical form: Prefilled syringe * Concentration: 0.9 % Saline * Route of Administration: Subcutaneous injection
Sponsors
Parexel
UCB BIOSCIENCES GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) with at least 3 months' symptom duration and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA and symptom duration of less than 5 years prior to the participation of this study * Active disease at Screening as defined by * Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.1 * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 * Spinal pain \> 4 on a 0 to 10 Numerical Rating Scale (NRS) (from BASDAI Item 2) * for modified New York (mNY) -negative subjects only: C-reactive Protein (CRP) \> upper limit of normal (ULN) and/or current evidence for sacroiliitis on the Screening Magnetic Resonance Imaging (MRI) * Inadequate response to, or contraindication to, or intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
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 primary failure to TNF antagonist therapy * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Part B Who Did Not Experienced a Flare | From Week 48 to Week 96 | A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥) 2.1 at 2 consecutive visits or an ASDAS greater than (\>) 3.5 at any visit during Part B up until Week 96. A participant qualified for Part B only if he achieved sustained remission after 48 weeks of Open-Label certolizumab pegol (CZP) treatment. Sustained remission was achieved when a participant had an ASDAS less than (\<) 1.3 at Week 32 or Week 36 (if ASDAS \< 1.3 at Week 32, it must have been \< 2.1 at Week 36; if ASDAS \< 2.1 at Week 32, it must have been \< 1.3 at Week 36) and an ASDAS \< 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A | Week 48 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: * ASDAS-Inactive Disease (ASDAS-ID): ASDAS \< 1.3 * ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, \< 2.1 * ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 * ASDAS-very High Disease activity (ASDAS-vHD): ASDAS \> 3.5 Missing data were handled using last observation carried forward (LOCF) methods. |
| Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A | Week 48 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: * ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline * ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods. |
| Time to Flare in Part B | From Week 48 to Week 96 | For those who met the criteria for flare (see primary efficacy variable), the time to flare was the length in days from randomization in Part B until the visit at which the criteria for flare were met. Participants who discontinued the study without meeting the criteria for flare were counted as experiencing a flare at the time of their last study visit. The time to flare was analyzed using Kaplan-Meier methods. If Kaplan-Meier Estimate was NA for all estimates then more than 75 % failed to meet the flare condition. Missing data were handled using non-response imputation (NRI) methods. |
| Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | Week 96 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: * ASDAS-Inactive Disease (ASDAS-ID): ASDAS \< 1.3 * ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, \< 2.1 * ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 * ASDAS-very High Disease activity (ASDAS-vHD): ASDAS \> 3.5 |
| Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | Week 96 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: * ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline * ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods. |
| Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B | Week 96 | The ASAS20 response was 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 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 absence of deterioration in the potential remaining domain \[deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit\]. Missing data were handled using non-response imputation (NRI) methods. |
| Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B | Week 96 | The ASAS40 response was defined as a relative improvement 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. Missing data were handled using non-response imputation (NRI) methods. |
| Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B | Week 96 | The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP). Missing data were handled using non-response imputation (NRI) methods. |
| Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B | Week 96 | The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20. Missing data were handled using non-response imputation (NRI) methods. |
| Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B | From Week 48 to Week 96 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as below the limit of quantification (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B | From Week 48 to Week 96 | The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) 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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B | From Week 48 to Week 96 | 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 Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B | From Week 48 to Week 96 | The BASMI 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 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B | Week 96 | The BASDAI50 response was defined as an improvement of at least 50 % in the BASDAI score relative to Baseline. Missing data were handled using non-response imputation (NRI) methods. |
| Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B | From Week 48 to Week 96 | 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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B | From Week 48 to Week 96 | 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. Active inflammation was 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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Percentage of Participants Achieving Sustained Remission at Week 48 in Part A | Week 48 | Sustained remission was achieved when a participant had an ASDAS less than (\<) 1.3 at Week 32 or Week 36 (if ASDAS \< 1.3 at Week 32, it must have been \< 2.1 at Week 36; if ASDAS \< 2.1 at Week 32, it must have been \< 1.3 at Week 36) and an ASDAS \< 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods. |
| Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | Escape Week 12 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: * ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline * ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline |
| Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | Escape Week 12 | The ASAS20 response was 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 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 absence of deterioration in the potential remaining domain \[deterioration was defined as a relative worsening of at least 20% and an absolute worsening of at least 1 unit\]. |
| Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | Escape Week 12 | The ASAS40 response was defined as a relative improvement 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. |
| Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | Escape Week 12 | The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP). |
| Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | Escape Week 12 | The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20. |
| Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B | From time of flare to Escape Week 12 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as below the limit of quantification (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | From time of flare to Escape Week 12 | The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) 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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | From time of flare to Escape 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 flare Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | From time of flare to Escape Week 12 | The BASMI 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 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | From time of flare to Escape 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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | From time of flare to Escape 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. Active inflammation was 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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Certolizumab Pegol (CZP) Plasma Concentration During the Study | From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication) | CZP plasma concentration was measured in micrograms per milliliter (μg/mL). Blood sample measurements that were deemed to be below the level of quantification, were set to half the lower level of quantification (LLOQ) for analysis purposes. Summary statistics were only displayed if at least two-thirds of the values were above the LLOQ and if n was greater or equal to (\>=) 4. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the PK of these patients. The CZP plasma concentration of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP. |
| Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study | From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication) | Treatment emergent ADAb status positive was defined as either baseline ADAb negative subjects having at least one ADAb confirmed positive sample post baseline or baseline ADAb positive subjects with at least one post baseline sample with \>= minimum significant ratio (MSR) increase from baseline on CZP treatment. Once determined positive, the highest titer during Part A and Part B (including Escape and Safety Follow up) was used to categorize the subject. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the immunogenicity of these patients. The ADAb titer of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP. |
| Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study | From Screening Period (Week -5 to Week -1) until Week 48 | An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study | From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication) | An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date prior to the start date of escape CZP full-dose therapy were included. |
| Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study | From time of flare to Escape Week 12 | An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date after or on the start date of escape CZP full-dose therapy were included. |
| Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | Escape Week 12 | The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: * ASDAS-Inactive Disease (ASDAS-ID): ASDAS \< 1.3 * ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, \< 2.1 * ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 * ASDAS-very High Disease activity (ASDAS-vHD): ASDAS \> 3.5 |
Countries
Belgium, Bulgaria, Czechia, France, Germany, Hungary, Netherlands, Poland, Romania, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study started to enroll patients in July 2015 and concluded in April 2019.
Pre-assignment details
The study included 2 parts: Part A with a Screening Period (up to 5 Weeks) and an Open-Label Period (Week 0 to Week 48) and Part B with a Double-Blind Period (Week 48 to Week 96) and a Safety Follow-Up Period (10 weeks after the last dose of study medication). Participant Flow refers to the Open-Label Set.
Participants by arm
| Arm | Count |
|---|---|
| Certolizumab Pegol Open-Label Participants in this arm 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 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B. | 736 |
| Total | 736 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Completed Part A, Did Not Enter Part B | Lack of Efficacy | 2 | 0 | 0 | 0 |
| Completed Part A, Did Not Enter Part B | The subject was not eligible for Part B | 341 | 0 | 0 | 0 |
| Completed Part A, Did Not Enter Part B | Withdrawal by Subject | 3 | 0 | 0 | 0 |
| Part A: Open-Label Period | Adverse Event | 31 | 0 | 0 | 0 |
| Part A: Open-Label Period | Lack of Efficacy | 5 | 0 | 0 | 0 |
| Part A: Open-Label Period | Lost to Follow-up | 5 | 0 | 0 | 0 |
| Part A: Open-Label Period | Medical monitor decision | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | New medical history available | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | Non-compliance | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | Participant did not attend week 48 visit | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | Pregnancy | 2 | 0 | 0 | 0 |
| Part A: Open-Label Period | Protocol Violation | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | Screening failure (detected too late) | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | Sponsor directive | 1 | 0 | 0 | 0 |
| Part A: Open-Label Period | Withdrawal by Subject | 27 | 0 | 0 | 0 |
| Part B: Double-Blind Period | Adverse Event | 0 | 0 | 1 | 3 |
| Part B: Double-Blind Period | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Part B: Double-Blind Period | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Part B: Double-Blind Period | Miscalculation | 0 | 1 | 0 | 0 |
| Part B: Double-Blind Period | Patient was moved from the country | 0 | 0 | 0 | 1 |
| Part B: Double-Blind Period | Planning pregnancy | 0 | 1 | 0 | 0 |
| Part B: Double-Blind Period | Subject did not complete all visits | 0 | 1 | 0 | 0 |
| Part B: Double-Blind Period | Week 94 missed | 0 | 0 | 1 | 0 |
| Part B: Double-Blind Period | Withdrawal by Subject | 0 | 8 | 7 | 2 |
Baseline characteristics
| Characteristic | Certolizumab Pegol Open-Label |
|---|---|
| Age, Categorical <=18 years | 7 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 729 Participants |
| Age, Continuous | 32.9 years STANDARD_DEVIATION 7 |
| Race/Ethnicity, Customized American indian/alaskan native | 2 Participants |
| Race/Ethnicity, Customized Asian | 38 Participants |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Missing | 9 Participants |
| Race/Ethnicity, Customized Other/Mixed | 5 Participants |
| Race/Ethnicity, Customized White | 681 Participants |
| Sex: Female, Male Female | 222 Participants |
| Sex: Female, Male Male | 514 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 736 | 0 / 103 | 0 / 104 | 0 / 105 | 0 / 72 | 0 / 6 | 0 / 15 |
| other Total, other adverse events | 188 / 736 | 25 / 103 | 31 / 104 | 26 / 105 | 20 / 72 | 5 / 6 | 7 / 15 |
| serious Total, serious adverse events | 44 / 736 | 0 / 103 | 5 / 104 | 0 / 105 | 0 / 72 | 1 / 6 | 0 / 15 |
Outcome results
Primary
Percentage of Participants in Part B Who Did Not Experienced a Flare
A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥) 2.1 at 2 consecutive visits or an ASDAS greater than (\>) 3.5 at any visit during Part B up until Week 96. A participant qualified for Part B only if he achieved sustained remission after 48 weeks of Open-Label certolizumab pegol (CZP) treatment. Sustained remission was achieved when a participant had an ASDAS less than (\<) 1.3 at Week 32 or Week 36 (if ASDAS \< 1.3 at Week 32, it must have been \< 2.1 at Week 36; if ASDAS \< 2.1 at Week 32, it must have been \< 1.3 at Week 36) and an ASDAS \< 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Part B Who Did Not Experienced a Flare | 20.2 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Part B Who Did Not Experienced a Flare | 83.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Part B Who Did Not Experienced a Flare | 79.0 percentage of participants |
Comparison: Odds ratio (and corresponding p-value) resulted from a logistic regression model with factors for treatment, geographic region, and modified New York (mNY) classification for study participants who did not experience a flare. An odds ratio \> 1 indicates a study participant on CZP was more likely not to experience a flare than a study participant on placebo. Penalized maximum likelihood approach was used for logistic regression.p-value: <0.00195% CI: [9.605, 38.864]Regression, Logistic
Comparison: Odds ratio (and corresponding p-value) resulted from a logistic regression model with factors for treatment, geographic region, and modified New York (mNY) classification for study participants who did not experience a flare. An odds ratio \> 1 indicates a study participant on CZP was more likely not to experience a flare than a study participant on placebo. Penalized maximum likelihood approach was used for logistic regression.p-value: <0.00195% CI: [7.395, 27.955]Regression, Logistic
Secondary
Certolizumab Pegol (CZP) Plasma Concentration During the Study
CZP plasma concentration was measured in micrograms per milliliter (μg/mL). Blood sample measurements that were deemed to be below the level of quantification, were set to half the lower level of quantification (LLOQ) for analysis purposes. Summary statistics were only displayed if at least two-thirds of the values were above the LLOQ and if n was greater or equal to (\>=) 4. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the PK of these patients. The CZP plasma concentration of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP.
Time frame: From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Population: The Pharmacokinetic Set B (PKSB) consisted of all study participants from the Safety Set Part B (SSB) who provided at least 1 PK sample during Part B.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 96 | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 24 | 27.47 μg/mL | Geometric Coefficient of Variation 45.31 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Withdrawal Visit | 0.81 μg/mL | Geometric Coefficient of Variation 1802.4 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 72 | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 12 | 23.89 μg/mL | Geometric Coefficient of Variation 232.36 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 0/Flare Baseline | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 4 | 37.32 μg/mL | Geometric Coefficient of Variation 151.18 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 2 | 18.27 μg/mL | Geometric Coefficient of Variation 488.45 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 24 | 26.31 μg/mL | Geometric Coefficient of Variation 135.58 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 4 | 48.71 μg/mL | Geometric Coefficient of Variation 85.76 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 36 | 24.88 μg/mL | Geometric Coefficient of Variation 77.53 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 12 | 30.91 μg/mL | Geometric Coefficient of Variation 89.23 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Safety Follow-up | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 48/Part B Baseline | 36.28 μg/mL | Geometric Coefficient of Variation 74.18 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 60 | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Part A Baseline | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Withdrawal Escape Visit | 4.71 μg/mL | Geometric Coefficient of Variation 133329.3 |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 84 | NA μg/mL | — |
| Placebo Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Last Visit (Week 96) | 24.64 μg/mL | Geometric Coefficient of Variation 112.75 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 48/Part B Baseline | 36.59 μg/mL | Geometric Coefficient of Variation 84.36 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 96 | 24.76 μg/mL | Geometric Coefficient of Variation 97.6 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 0/Flare Baseline | 30.77 μg/mL | Geometric Coefficient of Variation 19.78 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Part A Baseline | NA μg/mL | — |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 4 | 53.39 μg/mL | Geometric Coefficient of Variation 30.93 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 84 | 26.57 μg/mL | Geometric Coefficient of Variation 44.9 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 72 | 26.36 μg/mL | Geometric Coefficient of Variation 105.58 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Withdrawal Visit | NA μg/mL | — |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 2 | 33.50 μg/mL | Geometric Coefficient of Variation 21.17 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 4 | 32.94 μg/mL | Geometric Coefficient of Variation 30.48 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 12 | 23.76 μg/mL | Geometric Coefficient of Variation 65.42 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 24 | NA μg/mL | — |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 36 | NA μg/mL | — |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Last Visit (Week 96) | 26.19 μg/mL | Geometric Coefficient of Variation 54.74 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Withdrawal Escape Visit | NA μg/mL | — |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Safety Follow-up | 0.52 μg/mL | Geometric Coefficient of Variation 1158.85 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 12 | 31.74 μg/mL | Geometric Coefficient of Variation 50.79 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 24 | 30.23 μg/mL | Geometric Coefficient of Variation 46.57 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 60 | 27.76 μg/mL | Geometric Coefficient of Variation 49.47 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 36 | NA μg/mL | — |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 84 | 8.00 μg/mL | Geometric Coefficient of Variation 113.48 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 60 | 6.95 μg/mL | Geometric Coefficient of Variation 178.27 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Last Visit (Week 96) | 18.59 μg/mL | Geometric Coefficient of Variation 95.75 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 72 | 7.61 μg/mL | Geometric Coefficient of Variation 176.39 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 48/Part B Baseline | 31.11 μg/mL | Geometric Coefficient of Variation 138.29 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 24 | 28.96 μg/mL | Geometric Coefficient of Variation 58.38 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Safety Follow-up | 0.14 μg/mL | Geometric Coefficient of Variation 772.54 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 2 | 15.43 μg/mL | Geometric Coefficient of Variation 124.1 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 0/Flare Baseline | 12.70 μg/mL | Geometric Coefficient of Variation 98.45 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 4 | 48.92 μg/mL | Geometric Coefficient of Variation 43.17 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 4 | 18.43 μg/mL | Geometric Coefficient of Variation 79.93 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Withdrawal Visit | 0.30 μg/mL | Geometric Coefficient of Variation 2621.06 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 12 | 19.14 μg/mL | Geometric Coefficient of Variation 136.22 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 96 | 7.16 μg/mL | Geometric Coefficient of Variation 131.76 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Week 12 | 30.69 μg/mL | Geometric Coefficient of Variation 56.82 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Escape Week 24 | 19.23 μg/mL | Geometric Coefficient of Variation 66.68 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Certolizumab Pegol (CZP) Plasma Concentration During the Study | Part A Baseline | NA μg/mL | — |
Secondary
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as below the limit of quantification (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From time of flare to Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.~The number of participants analyzed reflects Escape Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -2.18 scores on a scale | Standard Deviation 1.13 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.56 scores on a scale | Standard Deviation 0.64 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.83 scores on a scale | Standard Deviation 0.94 |
Secondary
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as below the limit of quantification (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B | 1.66 scores on a scale | Standard Error 0.11 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B | 0.24 scores on a scale | Standard Error 0.077 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B | 0.45 scores on a scale | Standard Error 0.077 |
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: <0.00195% CI: [-1.66, -1.17]Mixed Models Analysis
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: <0.00195% CI: [-1.45, -0.96]Mixed Models Analysis
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) 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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From time of flare to Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.~The number of participants analyzed reflects Escape Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -3.75 scores on a scale | Standard Deviation 2.52 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -1.55 scores on a scale | Standard Deviation 1.05 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -2.29 scores on a scale | Standard Deviation 2.35 |
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) 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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B | 3.02 scores on a scale | Standard Error 0.226 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B | 0.56 scores on a scale | Standard Error 0.176 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B | 0.78 scores on a scale | Standard Error 0.176 |
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: <0.00195% CI: [-2.99, -1.94]Mixed Models Analysis
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: <0.00195% CI: [-2.77, -1.72]Mixed Models Analysis
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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 flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From time of flare to Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.~The number of participants analyzed reflects Escape Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -2.52 scores on a scale | Standard Deviation 2.46 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.72 scores on a scale | Standard Deviation 0.7 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -1.83 scores on a scale | Standard Deviation 2.38 |
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B
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 Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B | 1.90 scores on a scale | Standard Error 0.233 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B | 0.32 scores on a scale | Standard Error 0.198 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B | 0.46 scores on a scale | Standard Error 0.205 |
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: <0.00195% CI: [-2.04, -1.11]Mixed Models Analysis
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: <0.00195% CI: [-1.9, -0.96]Mixed Models Analysis
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
The BASMI 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 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From time of flare to Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.~The number of participants analyzed reflects Escape Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.43 scores on a scale | Standard Deviation 0.58 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.27 scores on a scale | Standard Deviation 0.35 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.26 scores on a scale | Standard Deviation 0.3 |
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B
The BASMI 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 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B | 0.21 scores on a scale | Standard Error 0.105 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B | 0.00 scores on a scale | Standard Error 0.065 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B | -0.03 scores on a scale | Standard Error 0.068 |
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: =0.07495% CI: [-0.42, 0.02]Mixed Models Analysis
Comparison: An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.p-value: =0.03695% CI: [-0.46, -0.02]Mixed Models Analysis
Secondary
Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B
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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From time of flare to Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.~The number of participants analyzed reflects Escape Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | -9.3 scores on a scale | Standard Deviation 13.2 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | 0.0 scores on a scale | Standard Deviation 0 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | 0.2 scores on a scale | Standard Deviation 3.1 |
Secondary
Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B
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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.~The number of participants analyzed reflects Week 96.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B | 1.1 scores on a scale | Standard Deviation 3.6 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B | 0.2 scores on a scale | Standard Deviation 2.4 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B | 0.6 scores on a scale | Standard Deviation 3.8 |
Comparison: Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal.~Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used.~ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.p-value: =0.19595% CI: [-2.5, 0.51]ANCOVA
Comparison: Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal.~Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used.~ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.p-value: =0.43295% CI: [-2.11, 0.91]ANCOVA
Secondary
Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B
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. Active inflammation was 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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From time of flare to Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.~The number of participants analyzed reflects Escape Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | -2.3 scores on a scale | Standard Deviation 4.6 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | 0.0 scores on a scale | Standard Deviation 0 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B | -0.3 scores on a scale | Standard Deviation 1 |
Secondary
Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B
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. Active inflammation was 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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.~The number of participants analyzed reflects Week 96.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Double-Blind (RS) | Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B | 0.4 scores on a scale | Standard Deviation 0.9 |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B | 0.0 scores on a scale | Standard Deviation 0.8 |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B | 0.0 scores on a scale | Standard Deviation 0.8 |
Comparison: Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal.~Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used.~ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.p-value: =0.0495% CI: [-0.78, -0.02]ANCOVA
Comparison: Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal.~Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used.~ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.p-value: =0.07495% CI: [-0.73, 0.03]ANCOVA
Secondary
Percentage of Participants Achieving Sustained Remission at Week 48 in Part A
Sustained remission was achieved when a participant had an ASDAS less than (\<) 1.3 at Week 32 or Week 36 (if ASDAS \< 1.3 at Week 32, it must have been \< 2.1 at Week 36; if ASDAS \< 2.1 at Week 32, it must have been \< 1.3 at Week 36) and an ASDAS \< 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 48
Population: The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of investigational medicinal product (IMP) in the Open-Label Period of the study (Part A).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants Achieving Sustained Remission at Week 48 in Part A | 43.9 percentage of participants |
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: * ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline * ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline
Time frame: Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-CII | 84.5 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-MI | 49.3 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-CII | 16.7 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-MI | 0 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-CII | 46.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-MI | 13.3 percentage of participants |
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: * ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline * ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 48
Population: The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of IMP in the Open-Label Period of the study (Part A).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A | ASDAS-CII | 76.6 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A | ASDAS-MI | 56.1 percentage of participants |
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: * ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline * ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | ASDAS-MI | 10.6 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | ASDAS-CII | 21.2 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | ASDAS-MI | 67.3 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | ASDAS-CII | 82.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | ASDAS-CII | 75.2 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B | ASDAS-MI | 58.1 percentage of participants |
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.p-value: <0.00195% CI: [8.95, 35.961]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.p-value: <0.00195% CI: [5.952, 21.778]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.p-value: <0.00195% CI: [8.333, 37.399]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.p-value: <0.00195% CI: [5.67, 24.822]Regression, Logistic
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: * ASDAS-Inactive Disease (ASDAS-ID): ASDAS \< 1.3 * ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, \< 2.1 * ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 * ASDAS-very High Disease activity (ASDAS-vHD): ASDAS \> 3.5
Time frame: Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-ID | 63.4 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-MD | 26.8 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-HD | 8.5 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-vHD | 1.4 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-MD | 50.0 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-vHD | 0 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-ID | 16.7 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-HD | 33.3 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-ID | 60.0 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-HD | 20.0 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-MD | 20.0 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B | ASDAS-vHD | 0 percentage of participants |
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: * ASDAS-Inactive Disease (ASDAS-ID): ASDAS \< 1.3 * ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, \< 2.1 * ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 * ASDAS-very High Disease activity (ASDAS-vHD): ASDAS \> 3.5 Missing data were handled using last observation carried forward (LOCF) methods.
Time frame: Week 48
Population: The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of IMP in the Open-Label Period of the study (Part A).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A | ASDAS-MD | 22.8 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A | ASDAS-ID | 52.5 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A | ASDAS-HD | 18.9 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A | ASDAS-vHD | 5.9 percentage of participants |
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B
The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: * ASDAS-Inactive Disease (ASDAS-ID): ASDAS \< 1.3 * ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, \< 2.1 * ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 * ASDAS-very High Disease activity (ASDAS-vHD): ASDAS \> 3.5
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-HD | 16.7 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-vHD | 0 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-ID | 58.3 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-MD | 25.0 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-HD | 0 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-MD | 13.8 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-vHD | 0 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-ID | 86.2 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-vHD | 0 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-ID | 69.9 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-MD | 22.9 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B | ASDAS-HD | 7.2 percentage of participants |
Secondary
Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date after or on the start date of escape CZP full-dose therapy were included.
Time frame: From time of flare to Escape Week 12
Population: The Escape Therapy Set (ETS) consisted of all study participants from the Flared Set (FS) who received at least 1 dose of escape treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study | 51.4 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study | 83.3 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study | 46.7 percentage of participants |
Secondary
Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From Screening Period (Week -5 to Week -1) until Week 48
Population: The Safety Set (SS) consisted of all study participants in the Enrolled Set (ES) who received at least 1 dose of investigational medicinal product (IMP).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study | Screening Period (Week -5 to Week -1) | 7.3 percentage of participants |
| Placebo Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study | Open-Label Period (Week 0 to Week 48) | 67.9 percentage of participants |
Secondary
Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date prior to the start date of escape CZP full-dose therapy were included.
Time frame: From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Population: The Safety Set Part B (SSB) consisted of all study participants in the Randomized Set (RS) who received at least 1 dose of IMP in the Double-Blind Period of the study (Part B).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study | 54.4 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study | 57.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study | 61.0 percentage of participants |
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASAS20 response was 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 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 absence of deterioration in the potential remaining domain \[deterioration was defined as a relative worsening of at least 20% and an absolute worsening of at least 1 unit\].
Time frame: Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 83.3 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 50.0 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 64.3 percentage of participants |
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B
The ASAS20 response was 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 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 absence of deterioration in the potential remaining domain \[deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit\]. Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B | 23.1 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B | 85.6 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B | 78.1 percentage of participants |
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [9.851, 41.439]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [6.275, 23.218]Regression, Logistic
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASAS40 response was defined as a relative improvement 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.
Time frame: Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 69.4 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 16.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 50.0 percentage of participants |
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B
The ASAS40 response was defined as a relative improvement 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. Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B | 21.2 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B | 84.6 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B | 73.3 percentage of participants |
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [10.21, 42.744]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [5.456, 19.738]Regression, Logistic
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
Time frame: Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 60.6 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 16.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 7.1 percentage of participants |
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B
The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP). Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B | 12.5 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B | 70.2 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B | 62.9 percentage of participants |
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [8.211, 34.785]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [5.954, 24.476]Regression, Logistic
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
Time frame: Escape Week 12
Population: The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 66.7 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 16.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B | 50.0 percentage of participants |
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B
The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20. Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B | 17.3 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B | 77.9 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B | 70.5 percentage of participants |
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [8.561, 34.085]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [5.939, 22.278]Regression, Logistic
Secondary
Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B
The BASDAI50 response was defined as an improvement of at least 50 % in the BASDAI score relative to Baseline. Missing data were handled using non-response imputation (NRI) methods.
Time frame: Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B | 22.1 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B | 83.7 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B | 77.1 percentage of participants |
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [9.084, 36.898]Regression, Logistic
Comparison: Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.p-value: <0.00195% CI: [6.255, 23.098]Regression, Logistic
Secondary
Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study
Treatment emergent ADAb status positive was defined as either baseline ADAb negative subjects having at least one ADAb confirmed positive sample post baseline or baseline ADAb positive subjects with at least one post baseline sample with \>= minimum significant ratio (MSR) increase from baseline on CZP treatment. Once determined positive, the highest titer during Part A and Part B (including Escape and Safety Follow up) was used to categorize the subject. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the immunogenicity of these patients. The ADAb titer of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP.
Time frame: From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Population: The Pharmacokinetic Set B (PKSB) consisted of all study participants from the Safety Set Part B (SSB) who provided at least 1 PK sample during Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Double-Blind (RS) | Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study | 100 percentage of participants |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study | 96.1 percentage of participants |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study | 100 percentage of participants |
Secondary
Time to Flare in Part B
For those who met the criteria for flare (see primary efficacy variable), the time to flare was the length in days from randomization in Part B until the visit at which the criteria for flare were met. Participants who discontinued the study without meeting the criteria for flare were counted as experiencing a flare at the time of their last study visit. The time to flare was analyzed using Kaplan-Meier methods. If Kaplan-Meier Estimate was NA for all estimates then more than 75 % failed to meet the flare condition. Missing data were handled using non-response imputation (NRI) methods.
Time frame: From Week 48 to Week 96
Population: The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Double-Blind (RS) | Time to Flare in Part B | 113 days |
| Certolizumab Pegol 200 mg Q2W Double-Blind (RS) | Time to Flare in Part B | 371 days |
| Certolizumab Pegol 200 mg Q4W Double-Blind (RS) | Time to Flare in Part B | NA days |
Comparison: P-values were from stratified log-rank test comparing the Certolizumab pegol 200 mg Q2W Double-Blind (RS) group with the Placebo Double-Blind (RS) group (Geographic region and modified New York (mNY) classification were used as stratification factors).p-value: <0.001Log Rank
Comparison: P-values were from stratified log-rank test comparing the Certolizumab pegol 200 mg Q4W Double-Blind (RS) group with the Placebo Double-Blind (RS) group (Geographic region and modified New York (mNY) classification were used as stratification factors).p-value: <0.001Log Rank