Study to Evaluate Maintenance of Sustained Remission of axSpA With CZP Compared to Placebo (C-OPTIMISE)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02505542 |
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Recruitment Status :
Completed
First Posted : July 22, 2015
Results First Posted : April 21, 2020
Last Update Posted : December 17, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Axial Spondyloarthrithis Ankylosing Spondylitis | Biological: Certolizumab Pegol Other: Placebo | Phase 3 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 736 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Open-label (Part A) Followed by a Randomized, Double-blind, Parallel-group, Placebo Controlled Study (Part B) to Evaluate Maintenance of Remission in Subjects With Active Axial Spondyloarthritis (axSpA) Receiving Either Certolizumab Pegol 200 mg Q2W or 200 mg Q4W as Compared to Placebo |
| Actual Study Start Date : | July 2015 |
| Actual Primary Completion Date : | February 2019 |
| Actual Study Completion Date : | April 2019 |
| Arm | Intervention/treatment |
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Open-label Certolizumab Pegol
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). Subjects in sustained remission at Week 48 are eligible for randomization into Part B.
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Biological: Certolizumab Pegol
Other Names:
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Experimental: Double-blind Certolizumab Pegol 200 mg Q2W
Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
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Biological: Certolizumab Pegol
Other Names:
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Experimental: Double-blind Certolizumab Pegol 200 mg Q4W
Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP is not received, subjects receive one injection of Placebo to maintain the study blind. |
Biological: Certolizumab Pegol
Other Names:
Other: Placebo
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Placebo Comparator: Placebo
One placebo injection is administered every 2 weeks from Week 48 onwards.
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Other: Placebo
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Placebo to CZP 200 mg Q2W escape
Subjects randomized to Placebo who meet flare criteria receive CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg is given every 2 weeks in open-label fashion.
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Biological: Certolizumab Pegol
Other Names:
Other: Placebo
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CZP 200 mg Q4W to CZP 200 mg Q2W escape
Subjects randomized to CZP 200 mg Q4W who meet flare criteria receive CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, subjects receive one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.
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Biological: Certolizumab Pegol
Other Names:
Other: Placebo
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CZP 200 mg Q2W to CZP 200 mg Q2W escape
Subjects randomized to CZP 200 mg Q2W who meet flare criteria receive CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, subjects receive one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.
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Biological: Certolizumab Pegol
Other Names:
Other: Placebo
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- Percentage of Participants in Part B Who Did Not Experienced a Flare [ Time Frame: 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.
- Percentage of Participants Achieving Sustained Remission at Week 48 in Part A [ Time Frame: 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) Disease Activity Categories at Week 48 in Part A [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B [ Time Frame: 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
- 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
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| Ages Eligible for Study: | 18 Years to 45 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02505542
Show 108 study locations
| Study Director: | UCB Cares | +1 844 599 2273(UCB) |
Documents provided by UCB Pharma ( UCB BIOSCIENCES GmbH ):
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | UCB BIOSCIENCES GmbH |
| ClinicalTrials.gov Identifier: | NCT02505542 |
| Other Study ID Numbers: |
AS0005 2015-000339-34 ( EudraCT Number ) |
| First Posted: | July 22, 2015 Key Record Dates |
| Results First Posted: | April 21, 2020 |
| Last Update Posted: | December 17, 2020 |
| Last Verified: | November 2020 |
|
Axial Spondyloarthritis axSpA Ankylosing Spondylitis Anti TNF-alpha Certolizumab Pegol |
Remission Spondylarthropathies Arthritis Spinal Diseases Immunosuppressive Agents |
|
Spondylitis Spondylarthritis Spondylitis, Ankylosing Axial Spondyloarthritis Bone Diseases, Infectious Infections Bone Diseases Musculoskeletal Diseases Spinal Diseases Arthritis |
Joint Diseases Spondylarthropathies Ankylosis Certolizumab Pegol Tumor Necrosis Factor Inhibitors Anti-Inflammatory Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |