Rheumatoid Arthritis
Conditions
Keywords
Certolizumab pegol, Cimzia, Rheumatoid Arthritis, Joint Disease, Chronic Arthritis
Brief summary
This is a Phase IIIb multicenter study to evaluate the safety and efficacy of certolizumab pegol (CZP) administered to patients with moderate-to-severe rheumatoid arthritis.
Detailed description
The treatment period starts with a 12-week, double-blind, placebo-controlled, randomized period followed by an open-label extension phase. In the double-blind phase, eligible patients are randomized (4:1 ratio) to receive either certolizumab pegol (CZP) or Placebo up to and including Week 10. The randomization will be stratified according to the three factors: concomitant use of methotrexate (MTX, Yes or No), prior anti-tumor necrosis factor (anti-TNF) use (Yes or No), and disease duration categories (\< 2 years or ≥ 2 years). From Week 12 all patients remaining in the study receive open-label CZP for a minimum 16 additional weeks until CZP is commercially available.
Interventions
400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
OTHERPlacebo
Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Sponsors
UCB Pharma
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
* Adult patient with established moderate to severe rheumatoid arthritis
Exclusion criteria
* All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment * Previous clinical trials and previous biological therapy that could interfere with the results in the present clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 20% (ACR20) Response at Week 12 | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use. | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years. | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| American College of Rheumatology 50% (ACR50) Response at Week 12 | Baseline, Week 12 | ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| American College of Rheumatology 70% (ACR70) Response at Week 12. | Baseline, Week 12 | ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12 | Baseline, Week 12 | DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12 | Baseline, Week 12 | SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12 | Baseline, Week 12 | CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12 | Week 12 | DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. |
| SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12 | Week 12 | SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. |
| CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12 | Week 12 | CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. |
| Change From Baseline in Tender Joint Count (TJC) at Week 12 | Baseline, Week 12 | TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in Swollen Joint Count (SJC) at Week 12 | Baseline, Week 12 | SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | Baseline, Week 12 | HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in C-reactive Protein (CRP) at Week 12 | Baseline, Week 12 | Change from baseline in CRP (mg/L) is computed as the ratio of Week 12 value divided by baseline value. A ratio less then 1 indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12 | Baseline, Week 12 | Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12 | Baseline, Week 12 | Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
| American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use. | Baseline, Week 12 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) |
| Time to Sustained American College of Rheumatology 20% (ACR20) Response | Baseline up to Week 12 | The time from randomization to sustained ACR20 response at 2 consecutive visits (at the latest on Week 12). |
| European League Against Rheumatism (EULAR) Response at Week 12 | Baseline, Week 12 | EULAR response (good response, moderate response, or no response) is defined based on the present value and improvement from baseline in DAS28(CRP) \[Disease Activity Score-28 (C-reactive protein)\]. |
| American College of Rheumatology 20% (ACR20) Response at Week 28 | Baseline, Week 28 | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS). This analysis was carried out using imputation. |
| American College of Rheumatology 50% (ACR50) Response at Week 28 | Baseline, Week 28 | ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS). This analysis was carried out using imputation. |
| American College of Rheumatology 70% (ACR70) Response at Week 28 | Baseline, Week 28 | ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS). This analysis was carried out using imputation. |
| Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28 | Baseline, Week 28 | DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28 | Baseline, Week 28 | SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28 | Baseline, Week 28 | CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28 | Week 28 | DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. This analysis was carried out using imputation. |
| SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28 | Week 28 | SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. This analysis was carried out using imputation. |
| CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28 | Week 28 | CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. This analysis was carried out using imputation. |
| Change From Baseline in Tender Joint Count (TJC) at Week 28 | Baseline, Week 28 | TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in Swollen Joint Count (SJC) at Week 28 | Baseline, Week 28 | SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28 | Baseline, Week 28 | HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in C-reactive Protein (CRP) at Week 28 | Baseline, Week 28 | Change from Baseline in CRP (mg/L) is computed as the ratio of the value at Week 28 divided by Baseline value. A ratio less then 1 indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28 | Baseline, Week 28 | Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28 | Baseline, Week 28 | Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28 | Baseline, Week 28 | Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM). |
| Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12 | Baseline, Week 12 | Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method. |
Countries
Canada, France, Germany, Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
The study started in July 2008 with subjects from the United States, Canada, France, Germany, Italy, the Netherlands, and Spain. The primary completion date occurred in March 2010, with study completion in March 2011.
Pre-assignment details
Of the 1648 subjects that were screened, 585 subjects had screen failures. Therefore, 1063 subjects were randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| Certolizumab Pegol (CZP) 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available. | 851 |
| Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available. | 212 |
| Total | 1,063 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Period | Adverse Event | 33 | 6 |
| Double-Blind Period | Lack of Efficacy | 6 | 6 |
| Double-Blind Period | Loss of efficacy | 3 | 0 |
| Double-Blind Period | Lost to Follow-up | 3 | 5 |
| Double-Blind Period | Other: Abnormal chest X-ray | 2 | 1 |
| Double-Blind Period | Other: Death | 1 | 0 |
| Double-Blind Period | Other: Detection of Hepatitis C Virus | 1 | 0 |
| Double-Blind Period | Other: History of adenoid grown | 1 | 0 |
| Double-Blind Period | Other: History of cancer | 1 | 0 |
| Double-Blind Period | Other: Inappropriate randomization | 1 | 0 |
| Double-Blind Period | Other: Inclusion/Exclusion criteria | 6 | 2 |
| Double-Blind Period | Other: Investigator Decision | 0 | 1 |
| Double-Blind Period | Other: Pregnancy | 1 | 0 |
| Double-Blind Period | Other: Prohibited medication taken | 2 | 2 |
| Double-Blind Period | Other: Protocol Violation | 2 | 0 |
| Double-Blind Period | Other: Screening failure | 1 | 0 |
| Double-Blind Period | Other: Site withdrew | 2 | 0 |
| Double-Blind Period | Other: Sponsor request | 1 | 0 |
| Double-Blind Period | Other: Stopped taking DMARD | 1 | 0 |
| Double-Blind Period | Other: Subject moved | 1 | 1 |
| Double-Blind Period | Other: subject withdrew consent | 1 | 1 |
| Double-Blind Period | Other: Transportation problems | 0 | 1 |
| Double-Blind Period | Withdrawal by Subject | 10 | 2 |
| Open-Label Period | Adverse Event | 29 | 4 |
| Open-Label Period | Lack of Efficacy | 30 | 8 |
| Open-Label Period | Loss of Efficacy | 6 | 1 |
| Open-Label Period | Lost to Follow-up | 28 | 4 |
| Open-Label Period | Other: Administration of Golimumab | 1 | 0 |
| Open-Label Period | Other: Cataract Surgery | 1 | 0 |
| Open-Label Period | Other: Completion Accidently Performed | 1 | 0 |
| Open-Label Period | Other: History of Basal Cell Carcinoma | 1 | 0 |
| Open-Label Period | Other: Investigator Decision | 1 | 0 |
| Open-Label Period | Other: Lack of Compliance | 1 | 1 |
| Open-Label Period | Other: Loss of Staff (unblinded) | 1 | 0 |
| Open-Label Period | Other: Medical Monitor Recommendation | 1 | 0 |
| Open-Label Period | Other: Moved | 1 | 0 |
| Open-Label Period | Other: Peripheral Neuropathy | 0 | 1 |
| Open-Label Period | Other: Sponsor Request | 3 | 0 |
| Open-Label Period | Withdrawal by Subject | 20 | 2 |
Baseline characteristics
| Characteristic | Certolizumab Pegol (CZP) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 207 Participants | 48 Participants | 255 Participants |
| Age, Categorical Between 18 and 65 years | 644 Participants | 164 Participants | 808 Participants |
| Age, Continuous | 55.4 years STANDARD_DEVIATION 12.43 | 53.9 years STANDARD_DEVIATION 12.66 | 55.1 years STANDARD_DEVIATION 12.49 |
| Region of Enrollment Canada | 65 participants | 17 participants | 82 participants |
| Region of Enrollment France | 14 participants | 0 participants | 14 participants |
| Region of Enrollment Germany | 154 participants | 44 participants | 198 participants |
| Region of Enrollment Italy | 13 participants | 2 participants | 15 participants |
| Region of Enrollment Netherlands | 4 participants | 0 participants | 4 participants |
| Region of Enrollment Spain | 26 participants | 8 participants | 34 participants |
| Region of Enrollment United States | 575 participants | 141 participants | 716 participants |
| Sex: Female, Male Female | 660 Participants | 169 Participants | 829 Participants |
| Sex: Female, Male Male | 191 Participants | 43 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 174 / 846 | 42 / 209 | 246 / 954 |
| serious Total, serious adverse events | 52 / 846 | 12 / 209 | 77 / 954 |
Outcome results
Primary
American College of Rheumatology 20% (ACR20) Response at Week 12
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: All 1063 subjects (851 CZP, 212 Placebo) included in the Full Analysis Set (FAS) are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 | 51.1 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 | 25.9 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use.
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS), 732 were in the concomitant methotrexate use stratum (589 CZP, 143 Placebo) and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use. | 52.5 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use. | 28.0 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS), 256 were in the disease duration less than 2 years stratum (206 CZP, 50 Placebo) and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years | 50.0 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years | 30.0 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years.
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS), 807 were in the disease duration greater than or equal to 2 years stratum (645 CZP, 162 Placebo) and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years. | 51.5 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years. | 24.7 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use.
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS), 331 were in the no concomitant methotrexate use stratum (262 CZP, 69 Placebo) and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use. | 48.1 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use. | 21.7 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS), 663 were in the no prior anti-tumor necrosis (anti-TNF) use stratum (531 CZP, 132 Placebo) and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use | 53.5 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use | 25.0 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS), 400 were in the prior anti-tumor necrosis (anti-TNF) use stratum (320 CZP, 80 Placebo) and are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use | 47.2 percentage of subjects |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use | 27.5 percentage of subjects |
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 28
ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS). This analysis was carried out using imputation.
Time frame: Baseline, Week 28
Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 20% (ACR20) Response at Week 28 | 58.5 percentage of subjects |
Secondary
American College of Rheumatology 50% (ACR50) Response at Week 12
ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 50% (ACR50) Response at Week 12 | 26.6 percentage of subjects |
| Placebo | American College of Rheumatology 50% (ACR50) Response at Week 12 | 9.9 percentage of subjects |
Secondary
American College of Rheumatology 50% (ACR50) Response at Week 28
ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS). This analysis was carried out using imputation.
Time frame: Baseline, Week 28
Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 50% (ACR50) Response at Week 28 | 35.0 percentage of subjects |
Secondary
American College of Rheumatology 70% (ACR70) Response at Week 12.
ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS)
Time frame: Baseline, Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 70% (ACR70) Response at Week 12. | 12.9 percentage of subjects |
| Placebo | American College of Rheumatology 70% (ACR70) Response at Week 12. | 2.8 percentage of subjects |
Secondary
American College of Rheumatology 70% (ACR70) Response at Week 28
ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1) Health Assessment Questionnaire-Disability Index (HAQ-DI), 2) C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS). This analysis was carried out using imputation.
Time frame: Baseline, Week 28
Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | American College of Rheumatology 70% (ACR70) Response at Week 28 | 17.4 percentage of subjects |
Secondary
CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity.
Time frame: Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12 | 8.3 percentage of subjects |
| Placebo | CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12 | 1.9 percentage of subjects |
Secondary
CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. This analysis was carried out using imputation.
Time frame: Week 28
Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28 | 12.1 percentage of subjects |
Secondary
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1024 (824 CZP, 200 Placebo) are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12 | -18.96 units on a scale | Standard Deviation 14.019 |
| Placebo | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12 | -10.93 units on a scale | Standard Deviation 14.494 |
Secondary
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 840 had observed values at Week 28 and Baseline and are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28 | -21.66 units on a scale | Standard Error 0.533 |
Secondary
Change From Baseline in C-reactive Protein (CRP) at Week 12
Change from baseline in CRP (mg/L) is computed as the ratio of Week 12 value divided by baseline value. A ratio less then 1 indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1046 (841 CZP, 205 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in C-reactive Protein (CRP) at Week 12 | 0.55 mg/L | Geometric Coefficient of Variation 111.417 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) at Week 12 | 1.05 mg/L | Geometric Coefficient of Variation 89.633 |
Secondary
Change From Baseline in C-reactive Protein (CRP) at Week 28
Change from Baseline in CRP (mg/L) is computed as the ratio of the value at Week 28 divided by Baseline value. A ratio less then 1 indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 851 had observed values at Week 28 and Baseline and are included in this analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in C-reactive Protein (CRP) at Week 28 | 0.59 mg/L | 95% Confidence Interval 122.929 |
Secondary
Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12
DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1037(834 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12 | -1.70 units on a scale | Standard Deviation 1.269 |
| Placebo | Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12 | -0.84 units on a scale | Standard Deviation 1.209 |
Secondary
Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28
DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 840 had observed values at Week 28 and Baseline and are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28 | -1.94 units on a scale | Standard Error 0.055 |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1029 (826 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.38 units on a scale | Standard Deviation 0.524 |
| Placebo | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.19 units on a scale | Standard Deviation 0.507 |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28
HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 854 had observed values at Week 28 and Baseline and are included in this analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28 | -0.46 units on a scale | Standard Error 0.023 |
Secondary
Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12
Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1038 (835 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12 | -22.1 mm | Standard Deviation 28.31 |
| Placebo | Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12 | -10.7 mm | Standard Deviation 27.32 |
Secondary
Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28
Change from Baseline in PAAP-VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 856 had observed values at Week 28 and Baseline and are included in this analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28 | -23.1 mm | Standard Error 1.06 |
Secondary
Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12
Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1038 (835 CZP, 203 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12 | -21.5 mm | Standard Deviation 27.78 |
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12 | -10.1 mm | Standard Deviation 26.24 |
Secondary
Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28
Change from Baseline in PtGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 857 had observed values at Week 28 and Baseline and are included in this analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28 | -23.0 mm | Standard Error 1.04 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12
Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1029 (827 CZP, 202 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12 | -31.2 mm | Standard Deviation 23.58 |
| Placebo | Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12 | -19.0 mm | Standard Deviation 25.15 |
Secondary
Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28
Change from Baseline in PhGADA-VAS (0 to 100 mm visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 848 had observed values at Week 28 and Baseline and are included in this analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28 | -35.6 mm | Standard Error 0.85 |
Secondary
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1024 (824 CZP, 200 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12 | -19.66 units on a scale | Standard Deviation 14.493 |
| Placebo | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12 | -10.78 units on a scale | Standard Deviation 15.172 |
Secondary
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 828 had observed values at Week 28 and Baseline and are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28 | -22.35 units on a scale | Standard Error 0.546 |
Secondary
Change From Baseline in Swollen Joint Count (SJC) at Week 12
SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1043 (838 CZP, 205 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | -6.4 units on a scale | Standard Deviation 5.57 |
| Placebo | Change From Baseline in Swollen Joint Count (SJC) at Week 12 | -3.6 units on a scale | Standard Deviation 5.64 |
Secondary
Change From Baseline in Swollen Joint Count (SJC) at Week 28
SJC is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as the value at Week 28 minus the baseline value. A negative value in change from baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 861 had observed values at Week 28 and Baseline and are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Swollen Joint Count (SJC) at Week 28 | -7.2 units on a scale | Standard Error 0.19 |
Secondary
Change From Baseline in Tender Joint Count (TJC) at Week 12
TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from baseline is computed as Week 12 value minus baseline value. A negative value in change from baseline indicates an improvement. This analysis was carried out using the Last Observation Carried Forward (LOCF) method.
Time frame: Baseline, Week 12
Population: Of the 1063 subjects in the Full Analysis Set (FAS) 1043 (838 CZP, 205 Placebo) are included in this analysis using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Tender Joint Count (TJC) at Week 12 | -7.4 units on a scale | Standard Deviation 7.13 |
| Placebo | Change From Baseline in Tender Joint Count (TJC) at Week 12 | -4.5 units on a scale | Standard Deviation 7.38 |
Secondary
Change From Baseline in Tender Joint Count (TJC) at Week 28
TJC is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from Baseline is computed as the value at Week 28 minus the Baseline value. A negative value in change from Baseline indicates an improvement. This analysis was done using a Mixed Effects Repeated Measures Model (MMRM).
Time frame: Baseline, Week 28
Population: Of the 954 subjects in the Open Label Set (OLS) 861 had observed values at Week 28 and Baseline and are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Certolizumab Pegol (CZP) | Change From Baseline in Tender Joint Count (TJC) at Week 28 | -8.6 units on a scale | Standard Error 0.26 |
Secondary
DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12
DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity.
Time frame: Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12 | 16.0 percentage of subjects |
| Placebo | DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12 | 5.7 percentage of subjects |
Secondary
DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28
DAS28(CRP) is calculated using tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/L), and Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in mm). A lower score indicates less disease activity. This analysis was carried out using imputation.
Time frame: Week 28
Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28 | 22.6 percentage of subjects |
Secondary
European League Against Rheumatism (EULAR) Response at Week 12
EULAR response (good response, moderate response, or no response) is defined based on the present value and improvement from baseline in DAS28(CRP) \[Disease Activity Score-28 (C-reactive protein)\].
Time frame: Baseline, Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Certolizumab Pegol (CZP) | European League Against Rheumatism (EULAR) Response at Week 12 | Good response | 28.9 percentage of subjects |
| Certolizumab Pegol (CZP) | European League Against Rheumatism (EULAR) Response at Week 12 | Moderate response | 44.5 percentage of subjects |
| Certolizumab Pegol (CZP) | European League Against Rheumatism (EULAR) Response at Week 12 | No response | 26.6 percentage of subjects |
| Placebo | European League Against Rheumatism (EULAR) Response at Week 12 | Good response | 10.4 percentage of subjects |
| Placebo | European League Against Rheumatism (EULAR) Response at Week 12 | Moderate response | 37.3 percentage of subjects |
| Placebo | European League Against Rheumatism (EULAR) Response at Week 12 | No response | 52.4 percentage of subjects |
Secondary
SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity.
Time frame: Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12 | 7.8 percentage of subjects |
| Placebo | SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12 | 1.9 percentage of subjects |
Secondary
SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), C-reactive protein (CRP in mg/dL), Patient's Global Assessment of Arthritis-Visual Analog Scale (PtGADA-VAS in cm), and Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS in cm). A lower score indicates less disease activity. This analysis was carried out using imputation.
Time frame: Week 28
Population: Since imputation was used, all 954 subjects from the Open Label (OL) Set are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28 | 11.4 percentage of subjects |
Secondary
Time to Sustained American College of Rheumatology 20% (ACR20) Response
The time from randomization to sustained ACR20 response at 2 consecutive visits (at the latest on Week 12).
Time frame: Baseline up to Week 12
Population: All 1063 subjects in the Full Analysis Set (FAS) are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Certolizumab Pegol (CZP) | Time to Sustained American College of Rheumatology 20% (ACR20) Response | 40.4 percentage of subjects |
| Placebo | Time to Sustained American College of Rheumatology 20% (ACR20) Response | 13.2 percentage of subjects |