Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Certolizumab Pegol, Cimzia
Brief summary
The objectives of this study are to verify the superiority in efficacy (American College of Rheumatology 20%: ACR20) and investigate the pharmacokinetics and safety of CDP870 versus placebo without coadministration of MTX in active RA patients in whom MTX cannot be administrated.
Interventions
Placebo given every 2 weeks until Week22 (SC)
DRUGCDP870
400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks until Week22 subcutaneously(SC)
Sponsors
UCB Japan Co. Ltd.
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a diagnosis of adult-onset RA of at least 6 months but not longer than 15 years in duration as defined by the 1987 American College of Rheumatology classification criteria. * Subjects must have active RA disease as defined by: * At least 6 tender joints and 6 swollen joints * ESR of 28 mm/hour or CRP of 2.0 mg/dL * Subjects who have failed to respond or have been resistant to at least one DMARD (including MTX) * Subjects in whom MTX cannot be administered for any of the reasons(incomplete response/safety concerns)
Exclusion criteria
* Patients who have a diagnosis of any other inflammatory arthritis * Patients who have a secondary, non-inflammatory type of arthritis (eg, osteoarthritis, fibromyalgia) * Patients who currently have, or who have a history of, a demyelinating or convulsive disease of the central nervous system (eg, multiple sclerosis, epilepsy) * Patients who have NYHA (New York Heart Association) Class III or IV congestive heart failure * Patients who currently have, or who have a history of, tuberculosis * Patients who have a high risk of infection (with a current infectious disease, a chronic infectious disease, a history of serious infectious disease) * Patients who currently have, or who have a history of, malignancy * Female patients who are breastfeeding or pregnant, who are of childbearing potential * Patients who previously received treatment with 2 or more anti-TNFα drugs or who previously failed to respond to treatment with 1 or more aint-TNFα drugs.
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 (PhGA-VAS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology 20% (ACR20) Response at Week 24 | Baseline, Week 24 | 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 (PhGA-VAS) |
Countries
Japan
Participant flow
Recruitment details
Subjects were recruited in Japan between 2008 and 2010.
Pre-assignment details
Participant flow results are based on the safety set.
Participants by arm
| Arm | Count |
|---|---|
| CDP870 200mg 400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2weeks | 116 |
| Placebo Placebo of CDP870 | 114 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lack of study drug administration | 1 | 1 |
| Overall Study | Protocol planed | 24 | 88 |
| Overall Study | Reason other than those above | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | CDP870 200mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 28 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 94 Participants | 88 Participants | 182 Participants |
| Age Continuous | 55.4 years STANDARD_DEVIATION 9.8 | 56.0 years STANDARD_DEVIATION 10.2 | 55.7 years STANDARD_DEVIATION 10 |
| Region of Enrollment Japan | 114 participants | 116 participants | 230 participants |
| Sex: Female, Male Female | 88 Participants | 83 Participants | 171 Participants |
| Sex: Female, Male Male | 26 Participants | 33 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 116 | 41 / 114 |
| serious Total, serious adverse events | 13 / 116 | 3 / 114 |
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 (PhGA-VAS)
Time frame: Baseline, Week 12
Population: All 230 subjects (116 CDP 200 mg, 114 Placebo) included in the Full Analysis Set (FAS) are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CDP870 200mg | American College of Rheumatology 20% (ACR20) Response at Week 12 | 67.2 percentage of participants |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 | 14.9 percentage of participants |
Comparison: For ACR20 responder rate at Week 12, comparison between the CDP870 200 mg group and the placebo group was performed.p-value: <0.05Regression, Logistic
Secondary
American College of Rheumatology 20% (ACR20) Response at Week 24
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 (PhGA-VAS)
Time frame: Baseline, Week 24
Population: All 230 subjects (116 CDP 200 mg, 114 Placebo) included in the Full Analysis Set (FAS) are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CDP870 200mg | American College of Rheumatology 20% (ACR20) Response at Week 24 | 63.8 percentage of participants |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 24 | 11.4 percentage of participants |
p-value: <0.05Regression, Logistic