- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01147341
Can TNF-Alpha Incomplete Secondary Responders Attain a Safe and Efficacious Response Switching to Cimzia
Can TNF-Alpha Incomplete Secondary Responders Attain a Safe and Efficacious Response By Switching to Certolizumab Pegol (Cimzia)? A Phase IV, Randomized, Multi-Center, Double-Blind, Twelve-Week Study Followed by a 12-Week Open-Label Phase
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase IV, randomized, multi-center, double-blind, parallel-group 12-week study of Cimzia with concomitant methotrexate (MTX) or other DMARD compared to MTX or other DMARD alone in patients with an inadequate secondary therapeutic response to a TNF-alpha inhibitor as defined above and active rheumatoid arthritis (RA) followed by a 12-week open-label phase with concomitant MTX or other DMARD and Cimzia.
Subjects must washout from the previous TNF inhibitor for at least 4 weeks prior to the baseline visit. Subjects unable to tolerate MTX must have been on a stable dose of another non-biologic DMARD for at least 3 months. Subjects' diagnosis of RA must be based on the 1987 Revised American Rheumatism Association Criteria for the Classification of Rheumatoid Arthritis.
Subjects will be screened for eligibility and, up to 28 days later, at the baseline visit, randomized to one of two treatment groups (2:1): Cimzia or placebo (in addition to concomitant MTX or other DMARD). All subjects will continue MTX/other DMARD at the same dose utilized prior to study entry.
After the Week 12 study visit, all subjects will have the opportunity to continue in the study on open-label Cimzia treatment (using an induction regimen for all subjects, regardless of their treatment in the blinded phase).
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Alabama
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Huntsville, Alabama, United States, 35801
- Rheumatology Associates of N. Alabama
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Arizona
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Peoria, Arizona, United States, 85381
- Sun Valley Arthritis Center, Ltd.
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Phoenix, Arizona, United States, 85037
- Arizona Arthritis and Rhematolgy Research
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Florida
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Sarasota, Florida, United States, 34239
- Sarasota Arthritis Research Center
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Nebraska
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Lincoln, Nebraska, United States, 68516
- Physician Research Collaboration, LLC
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Omaha, Nebraska, United States, 68114
- Westroads Medical Group
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New Jersey
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Morristown, New Jersey, United States, 07960
- Morristown Memorial Hospital
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New York
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Orchard Park, New York, United States, 14127
- Buffalo Rheumatology
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Smithtown, New York, United States, 11787
- Rheumatology Associates of Long Island
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Pennsylvania
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Duncansville, Pennsylvania, United States, 16635
- Altoona Center for Clinical Research
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West Virginia
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Clarksburg, West Virginia, United States, 26301
- Mountain State Clinical Research
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Wisconsin
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Oak Creek, Wisconsin, United States, 53154
- Rheumatology and Immunotherapy Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Have a diagnosis of RA at least 6 months
- Have received treatment with a TNF-alpha inhibitor
- Be receiving Methotrexate (with folic acid)at a dose of at least 10mg/week or another non-biologic DMARD if Methotrexate intolerant *Have at least 6 tender joint and 6 swollen joints*
- Have an CRP greater than or equal to ULN
- Availability of a chest x-ray that shows no evidence of active TB or infection
Exclusion Criteria:
- Prior exposure to Cimzia
- Prior treatment with B-cell depleting therapy
- No significant response to previous TNF inhibitor
- Congestive heart failure
- Clinically abnormal laboratory tests
- History of cancer
- Active TB
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo
Placebo (0.9% sodium chloride) given as 2 subcutaneous (sc) injections at weeks 0, 2, and 4, followed y 1 sc injection given an weeks 6, 8, and 10.
At week 12 subjects entered the open label phase.
Subjects received 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 12,14 and 16, followed by 1 sc injection at weeks 18, 20, and 22.
|
prefilled saline syringe
Other Names:
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Active Comparator: active treatment with Cimzia
400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 0, 2, and 4, followed by 1 sc injection at weeks 6, 8, and 10.
At week 12 subjects entered the open label phase.
Subjects received 400 mg of Cimzia (CZP) given as two 200 mg subcutaneous (sc) injections at weeks 12,14 and 16, followed by 1 sc injection at weeks 18, 20, and 22.
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prefilled 200mg Cimzia syringe SC q 2 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Subjects Achieving a Clinical Disease Activity Index (CDAI) Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 12
Time Frame: Baseline to week 12
|
The Clinical Disease Activity (CDAI)is a composite score.
Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22.
A CDAI reduction of 6.5 represents moderate improvement.
|
Baseline to week 12
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Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Time Frame: From Baseline to 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 (VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale(VAS). HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. |
From Baseline to Week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group at Week 12
Time Frame: Baseline to Week 12
|
ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. |
Baseline to Week 12
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Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP)
Time Frame: Baseline to Week 12
|
The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity. Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22 |
Baseline to Week 12
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Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Time Frame: Baseline to week 12
|
The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score. The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline). |
Baseline to week 12
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Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 12
Time Frame: Baseline to week 12
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The Clinical Disease Activity (CDAI)is a composite score.
Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22.
A CDAI reduction of 6.5 represents moderate improvement..
|
Baseline to week 12
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Subjects Achieving a CDAI Decrease of Greater Than or Equal to 10 Points in the Cimzia Treatment Group Compared to the Placebo Group at Week 24
Time Frame: Baseline to Week 24
|
The Clinical Disease Activity (CDAI)is a composite score.
Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 0-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22.
A CDAI reduction of 6.5 represents moderate improvement.
|
Baseline to Week 24
|
Proportion of Subjects Achieving an American College of Rheumatology 20% (ACR20) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Time Frame: Baseline to Week 24
|
ACR20 responders are subjects with at least 20% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. |
Baseline to Week 24
|
Proportion of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Time Frame: Baseline to Week 24
|
ACR50 responders are subjects with at least 50% improvement from baseline for tender joint cout (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, 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale, 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale. HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Visual Analog Scale (VAS) - assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad. |
Baseline to Week 24
|
Proportion of Subjects Achieving an American College of Rheuamtology Low Disease Activity Score and/or Remission Score in the Cimzia Group Compared to the Placebo Group as Calculated by DAS28 (CRP)
Time Frame: Baseline to Week 24
|
The Disease Activity Score-28-C-reactive Protein (DAS28-CRP)is a composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts (28 joints),C-Reactive Protein(CRP), and patient global assessment visual analog scale. A lower score indicated less disease activity. Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22 |
Baseline to Week 24
|
Proportion of Subjects Achieving a EULAR Good or Moderate Response Criteria in the Cimzia Treatment Group Compared to the Placebo Group
Time Frame: Baseline to Week 24
|
The EULAR (European League Against Rheumatism) response criteria is a classified response criteria which classifies the patients individual as non-, moderate or good responders dependent on the change and the level of the Disease Activity Score. The Disease Activity Score(DAS28) is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from baseline), or no response (absolute: >5.1 or <0.6 change from baseline). |
Baseline to Week 24
|
Proportion of Subjects Achieving a CDAI Score Decrease Greater Than or Equal to 13.9 Points in the CimZia Treatment Group Compared to the Placebo Group at Week 24
Time Frame: Baseline to Week 24
|
The Clinical Disease Activity (CDAI)is a composite score.
Clinical Disease Activity (CDAI) = SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs (including thumb IP)+ PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)+ EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity) Remission: CDAI ≤ 2.8; Low Disease Activity: CDAI > 2.8 and ≤ 10 ;Moderate Disease Activity: CDAI > 10 and ≤ 22; High Disease Activity: CDAI > 22.
A CDAI reduction of 6.5 represents moderate improvement.
|
Baseline to Week 24
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Michael H Schiff, MD
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CERT-001
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