Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Certolizumab Pegol, Cimzia
Brief summary
The objective of this trial is to investigate the efficacy (American College of Rheumatology 20% : ACR20) superiority of two dose regiments of CDP870 versus placebo in combination with MTX in active RA patients who have an incomplete response to MTX. The pharmacokinetics and immunogenicity profile of CDP870 will also be investigated to assess the extrapolability of foreign data to the Japanese population.
Interventions
DRUGCDP870 400mg
400mg CDP870 given every 2 weeks until Week22 (SC)
DRUGCDP870 200mg
400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2 weeks until Week22 (SC)
DRUGCDP870 100mg
200mg CDP870 given at Week0, 2, 4 and thereafter 100mg CDP870 given every 2 weeks until Week22 subcutaneously(SC)
given every 2 weeks until Week22 (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 9 tender joints and 9 swollen joints * ESR of 30 mm/hour or CRP of 1.5 mg/dL * Subjects must have received treatment with MTX for at least 6 months prior to the start of study drug administration. The dose of MTX must have remain fixed for at least 2 months prior to the study and the dose of MTX should be within 6 to 8 mg/week.
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 100mg 200mg CDP870 given at Week0, 2, 4 and thereafter 100mg CDP870 given every 2 weeks | 72 |
| CDP870 200mg 400mg CDP870 given at Week0, 2, 4 and thereafter 200mg CDP870 given every 2 weeks | 82 |
| CDP870 400mg 400mg CDP870 given every 2 weeks | 85 |
| Placebo Placebo given every 2 weeks | 77 |
| Total | 316 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 7 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 | 2 |
| Overall Study | Protocol planed withdrawal | 14 | 11 | 11 | 45 |
| Overall Study | Protocol Violation | 3 | 0 | 1 | 0 |
| Overall Study | Reason other than those above | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | CDP870 200mg | CDP870 400mg | CDP870 100mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 19 Participants | 11 Participants | 9 Participants | 44 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants | 66 Participants | 61 Participants | 68 Participants | 272 Participants |
| Age Continuous | 50.6 years STANDARD_DEVIATION 11.4 | 55.4 years STANDARD_DEVIATION 10.3 | 54.3 years STANDARD_DEVIATION 10.6 | 51.9 years STANDARD_DEVIATION 11.1 | 53.0 years STANDARD_DEVIATION 11 |
| Region of Enrollment Japan | 82 participants | 85 participants | 72 participants | 77 participants | 316 participants |
| Sex: Female, Male Female | 69 Participants | 69 Participants | 58 Participants | 66 Participants | 262 Participants |
| Sex: Female, Male Male | 13 Participants | 16 Participants | 14 Participants | 11 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 72 | 44 / 82 | 41 / 85 | 30 / 77 |
| serious Total, serious adverse events | 3 / 72 | 4 / 82 | 5 / 85 | 1 / 77 |
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 316 subjects (72 CDP 100 mg, 82 CDP 200 mg, 85 CDP 100 mg, 77 Placebo) included in the Full Analysis Set (FAS) are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CDP870 100mg | American College of Rheumatology 20% (ACR20) Response at Week 12 | 62.5 percentage of participants |
| CDP870 200mg | American College of Rheumatology 20% (ACR20) Response at Week 12 | 76.8 percentage of participants |
| CDP870 400mg | American College of Rheumatology 20% (ACR20) Response at Week 12 | 77.6 percentage of participants |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 12 | 28.6 percentage of participants |
Comparison: For ACR20 responder rate at Week 12, treatment comparisons versus placebo for the two CDP870 dose groups, the CDP870 200 mg group the CDP870 400 mg, were performed. The ACR20 responder rate in the CDP870 100 mg group was used for the secondary analysis.p-value: <0.025Regression, 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 316 subjects (72 CDP 100 mg, 82 CDP 200 mg, 85 CDP 100 mg, 77 Placebo) included in the Full Analysis Set (FAS) are included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CDP870 100mg | American College of Rheumatology 20% (ACR20) Response at Week 24 | 61.1 percentage of participants |
| CDP870 200mg | American College of Rheumatology 20% (ACR20) Response at Week 24 | 73.2 percentage of participants |
| CDP870 400mg | American College of Rheumatology 20% (ACR20) Response at Week 24 | 71.8 percentage of participants |
| Placebo | American College of Rheumatology 20% (ACR20) Response at Week 24 | 24.7 percentage of participants |
p-value: <0.05Regression, Logistic