Rheumatoid Arthritis
Conditions
Keywords
CDP870, Korea, CIMZIA
Brief summary
The objective of this trial is to compare the efficacy of Certolizumab (CZP) (CDP870) in combination with Methotrexate (MTX) to MTX alone in the treatment of signs and symptoms in patients with active rheumatoid arthritis (RA) who are incomplete responders to MTX.
Interventions
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 Week 22(SC)
DRUGMethotrexate
Received treatment with Methotrexate(MTX)for at least 24 weeks prior to the Baseline Visit. The dose and route of administration of MTX had to have been stable for at least 8 weeks prior to the Baseline Visit. The minimum stable dose of MTX allowed is 10mg weekly.
Sponsors
Korea Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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 * 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 * MTX (with or without folic acid) for at least 24 weeks prior to the Baseline visit, The dose of MTX and route of administration must have been stable for at least 8 weeks prior to the baseline visit. The minimum stable dose of MTX allowed is 10 mg weekly.
Exclusion criteria
* Any other inflammatory arthritis (e.g., psoriatic arthritis, ankylosing spondylitis or reactive arthritis) * Secondary, non-inflammatory type of arthritis (eg, osteoarthritis, fibromyalgia) * NYHA (New York Heart Association) Class III or IV congestive heart failure * current or history of, tuberculosis * history of chronic infection, recent serious or life-threatening infection (within 24 weeks , including herpes zoster), or any current sign or symptom that may indicate an infection (e.g., fever, cough) * High risk of infection * Have received any experimental non-biological therapy, within or outside a clinical trial in the 12 weeks prior to Baseline * Have received previous B-cell therapy (eg. Rituximab) * Have received any other biological therapy for RA within 24 weeks prior to Baseline visit, except for etanercept where a three month washout prior to baseline visit is acceptable * Have received previous treatment with a biological therapy for RA that resulted in a severe hypersensitivity reaction or an anaphylactic reaction * Failed to respond to previous treatment with an anti-TNF drug * Female breast feeding, pregnant or plan to become pregnant during the trial or for 12 weeks following the last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACR20 Responses at Week 24 | Week 24 | Achieving ACR20 means 20% or greater improvement in the number of tender joints, a 20% or more improvement in the number of swollen joints and a 20% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACR50 Responses at Week 12 | Week 12 | Achieving ACR50 means 50% or greater improvement in the number of tender joints, a 50% or more improvement in the number of swollen joints and a 50% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein. |
| ACR70 Responses at Week 12 | Week12 | Achieving ACR70 means 70% or greater improvement in the number of tender joints, a 70% or more improvement in the number of swollen joints and a 70% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein. |
| ACR 20 Responses at Week 12 | Week 12 | Achieving ACR20 means 20% or greater improvement in the number of tender joints, a 20% or more improvement in the number of swollen joints and a 20% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein. |
| ACR70 Responses at Week24 | Week 24 | — |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | Baseline and Week 24 | Range of HAQ-DI score: 0-3 This outcome measures changes of HAQ-DI score at Week 24 from Baseline. Lower score of HAQ-DI represents a better outcome. |
| ACR50 Responses at Week 24 | Week 24 | — |
Countries
South Korea
Participant flow
Recruitment details
Dates of the recruitment period : from 03 Nov 2009 to 16 Dec 2010 Types of location : clinic of rheumatology
Participants by arm
| Arm | Count |
|---|---|
| Placebo of CDP870+MTX 0.9% saline solution (preservative free) given as two 1ml injections of PFS at Baseline, Weeks 2 and 4, then every two weeks given as one 1ml injection of PFS. | 42 |
| CDP870 200mg+MTX Certolizumab pegol for subcutaneous injection is supplied in a 1 ml pre-filled syringe (PFS) for single use at dosage strength of 200 mg/ml. | 85 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Early study termination at the site | 1 | 0 |
| Overall Study | Investigator's opinion | 0 | 1 |
| Overall Study | Lack of Efficacy | 18 | 18 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo of CDP870+MTX | CDP870 200mg+MTX |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 4 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 110 Participants | 38 Participants | 72 Participants |
| Concomitant MTX dose | 13.5 mg/week STANDARD_DEVIATION 2.6 | 13.6 mg/week STANDARD_DEVIATION 2.8 | 13.4 mg/week STANDARD_DEVIATION 2.5 |
| Disease Duration | 6.3 years STANDARD_DEVIATION 4.5 | 6.0 years STANDARD_DEVIATION 5.1 | 6.4 years STANDARD_DEVIATION 4.2 |
| Health Assessment Questionnaire Disability Index (HAQ-DI) | 1.46 scores on a scale STANDARD_DEVIATION 0.69 | 1.53 scores on a scale STANDARD_DEVIATION 0.74 | 1.43 scores on a scale STANDARD_DEVIATION 0.67 |
| Number of previous disease-modifying anti-rheumatoid drugs (DMARDs) | 3.3 drugs/participants STANDARD_DEVIATION 1.4 | 3.2 drugs/participants STANDARD_DEVIATION 1.5 | 3.3 drugs/participants STANDARD_DEVIATION 1.3 |
| Sex: Female, Male Female | 112 Participants | 37 Participants | 75 Participants |
| Sex: Female, Male Male | 15 Participants | 5 Participants | 10 Participants |
| Swollen Joint Count | 16.41 Joints/participants STANDARD_DEVIATION 9.66 | 17.31 Joints/participants STANDARD_DEVIATION 11.18 | 15.96 Joints/participants STANDARD_DEVIATION 8.86 |
| Tender/Painful Joint Count | 25.04 Joints/participants STANDARD_DEVIATION 14.44 | 25.05 Joints/participants STANDARD_DEVIATION 14.61 | 25.04 Joints/participants STANDARD_DEVIATION 14.44 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 42 | 52 / 85 |
| serious Total, serious adverse events | 0 / 42 | 8 / 85 |
Outcome results
Primary
ACR20 Responses at Week 24
Achieving ACR20 means 20% or greater improvement in the number of tender joints, a 20% or more improvement in the number of swollen joints and a 20% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein.
Time frame: Week 24
Population: Full Analysis Set (FAS) Population The full set population will consist of all the subjects who were randomized and treated with the drug and received the primary efficacy evaluation at baseline. In the case of dosing administration error, analyses on the FAS population will be conducted according to the drug the subjects were randomized to.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo of CDP870+MTX | ACR20 Responses at Week 24 | 11 participants |
| CDP870 200mg+MTX | ACR20 Responses at Week 24 | 54 participants |
Secondary
ACR 20 Responses at Week 12
Achieving ACR20 means 20% or greater improvement in the number of tender joints, a 20% or more improvement in the number of swollen joints and a 20% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein.
Time frame: Week 12
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo of CDP870+MTX | ACR 20 Responses at Week 12 | 15 participants |
| CDP870 200mg+MTX | ACR 20 Responses at Week 12 | 52 participants |
Secondary
ACR50 Responses at Week 12
Achieving ACR50 means 50% or greater improvement in the number of tender joints, a 50% or more improvement in the number of swollen joints and a 50% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein.
Time frame: Week 12
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo of CDP870+MTX | ACR50 Responses at Week 12 | 5 participants |
| CDP870 200mg+MTX | ACR50 Responses at Week 12 | 21 participants |
Secondary
ACR50 Responses at Week 24
Time frame: Week 24
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo of CDP870+MTX | ACR50 Responses at Week 24 | 8 participants |
| CDP870 200mg+MTX | ACR50 Responses at Week 24 | 35 participants |
Secondary
ACR70 Responses at Week 12
Achieving ACR70 means 70% or greater improvement in the number of tender joints, a 70% or more improvement in the number of swollen joints and a 70% or greater improvement in at least three of the five remaining core set measures: Patient's and physician's global assessments, Patient's assessment of pain, disability index based on the Health Assessment Questionnaire and C-reactive Protein.
Time frame: Week12
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo of CDP870+MTX | ACR70 Responses at Week 12 | 0 participants |
| CDP870 200mg+MTX | ACR70 Responses at Week 12 | 11 participants |
Secondary
ACR70 Responses at Week24
Time frame: Week 24
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo of CDP870+MTX | ACR70 Responses at Week24 | 1 participants |
| CDP870 200mg+MTX | ACR70 Responses at Week24 | 14 participants |
Secondary
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Range of HAQ-DI score: 0-3 This outcome measures changes of HAQ-DI score at Week 24 from Baseline. Lower score of HAQ-DI represents a better outcome.
Time frame: Baseline and Week 24
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo of CDP870+MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | -0.17 scores on a scale | Standard Deviation 0.7 |
| CDP870 200mg+MTX | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | -0.54 scores on a scale | Standard Deviation 0.51 |