Axial Spondyloarthritis, Nonradiographic Axial Spondyloarthritis, Nr-axSpA
Conditions
Keywords
Axial Spondyloarthritis, axSpA, Ankylosing Spondylitis, Anti TNF-alpha, Certolizumab Pegol, Nr-axSpA, Non-radiographic, Spondylarthropathies, Arthritis, Spinal Diseases, Immunosuppressive Agents
Brief summary
Patients with active Axial Spondyloarthritis without x-ray evidence of Ankylosing Spondylitis and with signs of inflammation will be randomly assigned to receive certolizumab pegol (CZP) 200 mg every two weeks or placebo. The primary objective is to demonstrate the efficacy of CZP in these patients.
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
UCB BIOSCIENCES GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old at the start of Screening Visit * A documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA * Subjects must have had back pain for at least 12 months before Screening * No sacroiliitis defined by Modified New York (mNY) criteria on sacroiliac (SI) x-rays * Active disease at Screening as defined by * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score \>= 4 * Spinal pain \>= 4 on a 0 to 10 Numerical Rating Scale (NRS) * Inadequate response to, have a contraindication to, or have been intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Exclusion criteria
* Diagnosis of AS or any other Inflammatory Arthritis * Prior treatment with any experimental biological agents for treatment of Axial SpondyloArthritis (SpA) * Exposure to more than 1 tumor necrosis factor (TNF)-antagonist or primary failure to TNF antagonist therapy * History of or current chronic or recurrent infections * Subjects with known Tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent Tuberculosis (LTB) * Recent live vaccination * Concurrent malignancy or a history of malignancy * Class III or IV congestive heart failure - New York Heart Association (NYHA) * Demyelinating disease of the central nervous system * Female subjects who are breastfeeding, pregnant or plan to become pregnant during the study or within 3 months following the last dose of the investigational product * Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52 | Week 52 | This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable. ASDAS-MI was achieved when there was a reduction (improvement) \>= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached. The ASDAS was calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm \[ln\] of the (CRP \[mg/L\] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is not active and 10 is very active). |
| Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12 | Week 12 | This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries. The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is not active and 10 is very active in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. |
| Certolizumab Pegol Plasma Concentration at Baseline | Baseline (Week 0) | Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL). |
| Certolizumab Pegol Plasma Concentration at Week 1 | Week 1 | Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Week 2 | Week 2 | Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Week 4 | Week 4 | Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Week 12 | Week 12 | Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Week 24 | Week 24 | Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Week 36 | Week 36 | Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Week 52 | Week 52 | Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL. |
| Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit | Follow-up Visit (up to Week 60) | Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL. Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ASQoL at Week 12 | From Baseline to Week 12 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in ASQoL at Week 24 | From Baseline to Week 24 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in ASQoL at Week 36 | From Baseline to Week 36 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in ASQoL at Week 48 | From Baseline to Week 48 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52 | Week 52 | The ASAS40 response was defined as relative improvements of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is not active and 10 is very active in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. |
| Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52 | Throughout the study conduct (up to Week 52) | The number of subjects with AU or new AU flares during the study treatment period. |
| Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study | From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Percentage of Subjects With Serious Adverse Events (SAEs) During the Study | From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) | A serious adverse event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is an infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. |
| Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study | From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52 | From Baseline to Week 52 | The nocturnal spinal pain experienced by subjects due to AS was measured by following question 'How much pain of your spine due to spondylitis do you have at night?'. The NRS ranged from 0 to 10, where 0 represented 'no pain' and 10 represented 'most severe pain'. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | From Baseline to Week 12 | The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | From Baseline to Week 52 | The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | From Baseline to Week 12 | The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | From Baseline to Week 52 | The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score | From Baseline to Week 12 | The Spondyloarthritis Research Consortium of Canada (SPARCC) scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52 | From Baseline to Week 52 | The number of subjects who did not have relevant changes to background medications during the study treatment period. A subject is without relevant changes to background medication if they do not have: the addition of a new disease-modifying antirheumatic drug (DMARD) or the change from one DMAR to another; the addition of an nonsteroidal anti-inflammatory drug (NSAID) or the change from one NSAID to another; an increased dose of chronic corticosteroids; the addition of a new chronic analgesic medication or increased dose in chronic analgesic medication; and they complete double-blind study treatment to Week 52. |
| Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 | From Baseline to Week 52 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in ASQoL at Week 1 | From Baseline to Week 1 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in ASQoL at Week 2 | From Baseline to Week 2 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in ASQoL at Week 4 | From Baseline to Week 4 | The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
Countries
Australia, Bulgaria, Canada, Czechia, Hungary, Poland, Russia, Taiwan, United States
Participant flow
Recruitment details
This study started to enroll participants in September 2015. The study included a Screening Period, up to 6 weeks before Baseline, a Double-Blind (DB) Period from Baseline (Week 0) to Week 52, that included the open label CZP (OL-CZP) treatment and other treatment (OT) and an Open Label Safety Follow-up Extension (SFE) Period, up to Week 156.
Pre-assignment details
The Participant Flow refers to the Randomized Set (RS).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo to certolizumab pegol (CZP) injections were administered every 2 weeks from Week 0 onwards. | 158 |
| CZP 200 mg Q2W Certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. | 159 |
| Total Title | 317 |
| Total | 634 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Period (Week 0 - 52) | Adverse Event | 6 | 3 | 0 |
| Double-Blind Period (Week 0 - 52) | As per suggestion | 0 | 1 | 0 |
| Double-Blind Period (Week 0 - 52) | Lack of Efficacy | 2 | 2 | 0 |
| Double-Blind Period (Week 0 - 52) | Lost to Follow-up | 1 | 0 | 0 |
| Double-Blind Period (Week 0 - 52) | Missing/Unspecified | 1 | 0 | 0 |
| Double-Blind Period (Week 0 - 52) | Not eligible | 0 | 1 | 0 |
| Double-Blind Period (Week 0 - 52) | Patient's decision | 0 | 1 | 0 |
| Double-Blind Period (Week 0 - 52) | Protocol Violation | 1 | 1 | 0 |
| Double-Blind Period (Week 0 - 52) | Study non-compliance | 1 | 1 | 0 |
| Double-Blind Period (Week 0 - 52) | Withdrawal by Subject | 3 | 7 | 0 |
| SFE Period (Week 52 - 156) | Adverse Event | 0 | 0 | 5 |
| SFE Period (Week 52 - 156) | Compassionate access | 0 | 0 | 2 |
| SFE Period (Week 52 - 156) | Decision of Patient | 0 | 0 | 1 |
| SFE Period (Week 52 - 156) | Investigator decision | 0 | 0 | 1 |
| SFE Period (Week 52 - 156) | Lack of Efficacy | 0 | 0 | 4 |
| SFE Period (Week 52 - 156) | Lost to Follow-up | 0 | 0 | 2 |
| SFE Period (Week 52 - 156) | Patient's personal reason | 0 | 0 | 1 |
| SFE Period (Week 52 - 156) | Patient travelling for study unable to continue | 0 | 0 | 1 |
| SFE Period (Week 52 - 156) | Return to standard-of-care /OL CZP | 0 | 0 | 1 |
| SFE Period (Week 52 - 156) | Subject withdrew consent due to traveling to site | 0 | 0 | 1 |
| SFE Period (Week 52 - 156) | Withdrawal by Subject | 0 | 0 | 18 |
Baseline characteristics
| Characteristic | Placebo | CZP 200 mg Q2W | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 154 Participants | 156 Participants | 310 Participants |
| Age, Continuous | 37.4 years STANDARD_DEVIATION 10.8 | 37.3 years STANDARD_DEVIATION 10.5 | 37.3 years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized Asian | 8 Participants | 5 Participants | 13 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other/mixed | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 148 Participants | 152 Participants | 300 Participants |
| Sex: Female, Male Female | 82 Participants | 81 Participants | 163 Participants |
| Sex: Female, Male Male | 76 Participants | 78 Participants | 154 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 158 | 0 / 159 | 0 / 96 | 0 / 20 | 0 / 243 |
| other Total, other adverse events | 59 / 158 | 75 / 159 | 27 / 96 | 7 / 20 | 69 / 243 |
| serious Total, serious adverse events | 4 / 158 | 8 / 159 | 3 / 96 | 1 / 20 | 15 / 243 |
Outcome results
Primary
Certolizumab Pegol Plasma Concentration at Baseline
Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
Time frame: Baseline (Week 0)
Population: The Safety Set (SS) consisted of all subjects who have received at least 1 dose of study medication. Note: None of the Safety Set subjects had Pharmacokinetic (PK) concentrations above the lower limit of quantification.
Primary
Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL. Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period.
Time frame: Follow-up Visit (up to Week 60)
Population: The SS consisted of all subjects who received at least 1 dose of study treatment. Only participants included, who had a SFU Visit at 8 weeks after Week 52/WD visit for those not participating in the SFE period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit | 0.2 µg/mL |
| CZP 200 mg Q2W (FAS) | Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit | NA µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 1
Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
Time frame: Week 1
Population: The SS consisted of all subjects who received at least 1 dose of study treatment. Note: No samples taken at Week 1 for the Placebo-\>OL CZP.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 1 | 50.5 µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 12
Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
Time frame: Week 12
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 12 | 29.1 µg/mL |
| CZP 200 mg Q2W (FAS) | Certolizumab Pegol Plasma Concentration at Week 12 | 30.5 µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 2
Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
Time frame: Week 2
Population: The SS consisted of all subjects who received at least 1 dose of study treatment. Note: No samples taken at Week 2 for the Placebo-\>OL CZP.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 2 | 36.4 µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 24
Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
Time frame: Week 24
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 24 | 23.5 µg/mL |
| CZP 200 mg Q2W (FAS) | Certolizumab Pegol Plasma Concentration at Week 24 | 24.8 µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 36
Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
Time frame: Week 36
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 36 | 24.0 µg/mL |
| CZP 200 mg Q2W (FAS) | Certolizumab Pegol Plasma Concentration at Week 36 | 22.9 µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 4
Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
Time frame: Week 4
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 4 | 54.6 µg/mL |
| CZP 200 mg Q2W (FAS) | Certolizumab Pegol Plasma Concentration at Week 4 | 48.8 µg/mL |
Primary
Certolizumab Pegol Plasma Concentration at Week 52
Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
Time frame: Week 52
Population: The SS consisted of all subjects who received at least 1 dose of study treatment. Note: No samples taken at OL Week 52 for the Placebo-\>OL CZP.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo (FAS) | Certolizumab Pegol Plasma Concentration at Week 52 | 22.6 µg/mL |
Primary
Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable. ASDAS-MI was achieved when there was a reduction (improvement) \>= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached. The ASDAS was calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm \[ln\] of the (CRP \[mg/L\] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is not active and 10 is very active).
Time frame: Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52 | 7.0 percentage of subjects |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52 | 47.2 percentage of subjects |
Comparison: Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region and Magnetic Resonance Imaging/C- Reactive Protein (MRI/CRP) classification.p-value: <0.00195% CI: [7.336, 31.623]Regression, Logistic
Primary
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries. The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is not active and 10 is very active in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Time frame: Week 12
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12 | 11.4 percentage of subjects |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12 | 47.8 percentage of subjects |
Comparison: Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region and MRI/CRP classification.p-value: <0.00195% CI: [4.127, 13.401]Regression, Logistic
Secondary
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 | -0.18 scores on a scale | Standard Error 0.04 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52 | -0.36 scores on a scale | Standard Error 0.03 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.00195% CI: [-0.25, -0.117]ANCOVA
Secondary
Change From Baseline in ASQoL at Week 1
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 1
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 1 | -0.03 scores on a scale | Standard Deviation 0.14 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 1 | -0.11 scores on a scale | Standard Deviation 0.21 |
Secondary
Change From Baseline in ASQoL at Week 12
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 12
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 12 | -0.08 scores on a scale | Standard Deviation 0.22 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 12 | -0.28 scores on a scale | Standard Deviation 0.26 |
Secondary
Change From Baseline in ASQoL at Week 2
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 2
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 2 | -0.03 scores on a scale | Standard Deviation 0.15 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 2 | -0.16 scores on a scale | Standard Deviation 0.23 |
Secondary
Change From Baseline in ASQoL at Week 24
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 24
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 24 | -0.09 scores on a scale | Standard Deviation 0.23 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 24 | -0.31 scores on a scale | Standard Deviation 0.27 |
Secondary
Change From Baseline in ASQoL at Week 36
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 36
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 36 | -0.11 scores on a scale | Standard Deviation 0.23 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 36 | -0.33 scores on a scale | Standard Deviation 0.29 |
Secondary
Change From Baseline in ASQoL at Week 4
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 4
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 4 | -0.06 scores on a scale | Standard Deviation 0.19 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 4 | -0.18 scores on a scale | Standard Deviation 0.23 |
Secondary
Change From Baseline in ASQoL at Week 48
The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 48
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in ASQoL at Week 48 | -0.10 scores on a scale | Standard Deviation 0.24 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in ASQoL at Week 48 | -0.34 scores on a scale | Standard Deviation 0.3 |
Secondary
Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52
The nocturnal spinal pain experienced by subjects due to AS was measured by following question 'How much pain of your spine due to spondylitis do you have at night?'. The NRS ranged from 0 to 10, where 0 represented 'no pain' and 10 represented 'most severe pain'. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52 | -2.1 scores on a scale | Standard Error 0.5 |
| CZP 200 mg Q2W (FAS) | Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52 | -4.0 scores on a scale | Standard Error 0.4 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.00195% CI: [-2.62, -1.18]ANCOVA
Secondary
Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score
The Spondyloarthritis Research Consortium of Canada (SPARCC) scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 12
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score | 0.200 scores on a scale | Standard Error 0.772 |
| CZP 200 mg Q2W (FAS) | Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score | -4.669 scores on a scale | Standard Error 0.77 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.00195% CI: [-6.4014, -3.336]ANCOVA
Secondary
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 12
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | -0.91 scores on a scale | Standard Error 0.22 |
| CZP 200 mg Q2W (FAS) | Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | -2.73 scores on a scale | Standard Error 0.21 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.00195% CI: [-2.25, -1.388]ANCOVA
Secondary
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 12
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | -0.38 scores on a scale | Standard Error 0.21 |
| CZP 200 mg Q2W (FAS) | Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | -2.07 scores on a scale | Standard Error 0.2 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.00195% CI: [-2.11, -1.282]ANCOVA
Secondary
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | -2.59 scores on a scale | Standard Error 0.37 |
| CZP 200 mg Q2W (FAS) | Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | -3.88 scores on a scale | Standard Error 0.27 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.00195% CI: [-1.909, -0.672]ANCOVA
Secondary
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | -1.44 scores on a scale | Standard Error 0.3 |
| CZP 200 mg Q2W (FAS) | Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI) | -3.03 scores on a scale | Standard Error 0.24 |
Comparison: From an ANCOVA model including scores at Baseline, treatment group, region and MRI/CRP classification.p-value: <0.000195% CI: [-2.132, -1.038]ANCOVA
Secondary
Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52
The number of subjects with AU or new AU flares during the study treatment period.
Time frame: Throughout the study conduct (up to Week 52)
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (FAS) | Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52 | 8 Participants |
| CZP 200 mg Q2W (FAS) | Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52 | 4 Participants |
Comparison: Odds ratio: CZP/PBO and p-value were calculated using logistic regression with factors for treatment, region and MRI/CRP classification.p-value: =0.24795% CI: [0.142, 1.653]Regression, Logistic
Secondary
Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52
The number of subjects who did not have relevant changes to background medications during the study treatment period. A subject is without relevant changes to background medication if they do not have: the addition of a new disease-modifying antirheumatic drug (DMARD) or the change from one DMAR to another; the addition of an nonsteroidal anti-inflammatory drug (NSAID) or the change from one NSAID to another; an increased dose of chronic corticosteroids; the addition of a new chronic analgesic medication or increased dose in chronic analgesic medication; and they complete double-blind study treatment to Week 52.
Time frame: From Baseline to Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (FAS) | Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52 | 48 Participants |
| CZP 200 mg Q2W (FAS) | Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52 | 115 Participants |
Comparison: Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region and MRI/CRP classification.p-value: <0.00195% CI: [3.8, 10.191]Regression, Logistic
Secondary
Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study | 1.9 percentage of subjects |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study | 1.9 percentage of subjects |
| Placebo->OL CZP (SS) | Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study | 3.1 percentage of subjects |
| CZP->OL CZP (SS) | Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study | 0 percentage of subjects |
| SFE OL CZP 200 mg Q2W (SS) | Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study | 2.5 percentage of subjects |
Secondary
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52
The ASAS40 response was defined as relative improvements of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is not active and 10 is very active in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
Time frame: Week 52
Population: The FAS consisted of all subjects in the RS who have received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52 | 15.8 percentage of subjects |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52 | 56.6 percentage of subjects |
Comparison: Odds ratio: CZP/Placebo and p-value were calculated using logistic regression with factors for treatment, region MRI/CRP classification.p-value: <0.00195% CI: [4.286, 12.636]Regression, Logistic
Secondary
Percentage of Subjects With Serious Adverse Events (SAEs) During the Study
A serious adverse event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is an infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Time frame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects With Serious Adverse Events (SAEs) During the Study | 2.5 percentage of subjects |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects With Serious Adverse Events (SAEs) During the Study | 5.0 percentage of subjects |
| Placebo->OL CZP (SS) | Percentage of Subjects With Serious Adverse Events (SAEs) During the Study | 3.1 percentage of subjects |
| CZP->OL CZP (SS) | Percentage of Subjects With Serious Adverse Events (SAEs) During the Study | 5.0 percentage of subjects |
| SFE OL CZP 200 mg Q2W (SS) | Percentage of Subjects With Serious Adverse Events (SAEs) During the Study | 6.2 percentage of subjects |
Secondary
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Population: The SS consisted of all subjects who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (FAS) | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study | 63.9 percentage of subjects |
| CZP 200 mg Q2W (FAS) | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study | 75.5 percentage of subjects |
| Placebo->OL CZP (SS) | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study | 59.4 percentage of subjects |
| CZP->OL CZP (SS) | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study | 65.0 percentage of subjects |
| SFE OL CZP 200 mg Q2W (SS) | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study | 61.3 percentage of subjects |