A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis (C-early)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01519791 |
|
Recruitment Status :
Completed
First Posted : January 27, 2012
Results First Posted : September 22, 2015
Last Update Posted : July 31, 2018
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatoid Arthritis | Biological: Certolizumab Pegol Other: Placebo Biological: Methotrexate | Phase 3 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 880 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate for Inducing and Sustaining Clinical Response in the Treatment of DMARD-Naïve Adults With Early Active Rheumatoid Arthritis |
| Study Start Date : | January 2012 |
| Actual Primary Completion Date : | July 2014 |
| Actual Study Completion Date : | September 2015 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: Certolizumab Pegol + Methotrexate |
Biological: Certolizumab Pegol
Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at a dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, Week 2 and Week 4, followed by a maintenance dose of 200 mg every 2 Weeks until Week 50. Other Names:
Biological: Methotrexate The MTX treatment is to be initiated at a dose of 10 mg per Week (oral tablets at the strength of 2.5 mg/tablet). The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8. Patients who could not tolerate ≥ 15 mg/week MTX by Week 8 were withdrawn while the maximum tolerated dose per patient (optimized dose) was maintained to Week 52.
Other Name: MTX |
| Placebo Comparator: Placebo + Methotrexate |
Other: Placebo
2 syringes Placebo at Baseline, Week 2 and Week 4, followed by 1 syringe Placebo every 2 Weeks. Biological: Methotrexate The MTX treatment is to be initiated at a dose of 10 mg per Week (oral tablets at the strength of 2.5 mg/tablet). The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8. Patients who could not tolerate ≥ 15 mg/week MTX by Week 8 were withdrawn while the maximum tolerated dose per patient (optimized dose) was maintained to Week 52.
Other Name: MTX |
- Percentage of Subjects in Sustained Remission at Week 52 [ Time Frame: Week 52 ]
Sustained remission is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at both Weeks 40 and 52.
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula:
0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
- Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52 [ Time Frame: Week 52 ]Sustained LDA is defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) ≤ 3.2 at both Weeks 40 and 52.
- Change From Baseline in Modified Total Sharp Score (mTSS) to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]Van der Heijde modified Total Sharp Score (mTSS) is a methodology to assess the degree of joint damage by quantifying the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively. The mTSS ranges from 0 to 448, with higher scores representing greater damage.
- Percentage of Subjects With Radiographic Non-progression From Baseline to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]Radiographic non-progression is defined as change in mTSS ≤ 0.5.
- Change From Baseline in the Joint Erosion Score to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
Erosions were assessed in 16 locations per hand and 6 joints per foot. Erosions for each hand location were scored from 0 to 5, with 0 indicating no erosion. Scores 1 to 5 may have included combinations of discrete erosion(s) and/or large erosions. Erosions for each foot joint were scored from 0 to 10, with 0 indicating no erosions.
The maximum possible erosion score for all 32-hand joints was 160. The maximum possible erosion score for all 12 feet joints was 120. Thus, the maximum possible total erosion score for hands and feet was 280.
- Change From Baseline in the Joint Narrowing Score to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]Joint space narrowing (JSN) was assessed in 15 locations per hand and 6 locations per foot. Joint space narrowing for each location was scored from 0 to 4, with 0 indicating no narrowing. The maximum possible score for JSN in all 30 hand joints was 120. The maximum possible score for JSN in all 12 feet joints was 48. Thus, the maximum possible total JSN score for Hands and feet was 168.
- Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]The assessments are based on a 20 % or greater improvement from Baseline in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
- Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]The assessments are based on a 50 % or greater improvement from Baseline in the number of tender joints, a 50 %, or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
- Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]The assessments are based on a 70 % or greater improvement from Baseline in the number of tender joints, a 70 %, or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
- Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria at Week 52 [ Time Frame: Week 52 ]
The ACR/EULAR 2011 remission criteria is defined as:
Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1, C-reactive protein (CRP) ≤ 1 mg/dl and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.
- Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 at Week 52 [ Time Frame: Week 52 ]CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
- Percentage of Subjects With Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 52 [ Time Frame: Week 52 ]SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
- Percentage of Subjects With Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52 [ Time Frame: Week 52 ]
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula:
0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity.
- Percentage of Subjects Meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice at Week 52 [ Time Frame: Week 52 ]
The 2011 ACR/EULAR remission criteria simplified for clinical practice is defined as:
Tender Joint Count (TJC) ≤ 1, Swollen Joint Count (SJC) ≤ 1 and Patient's Global Assessment of Disease Activity (PtGADA) ≤ 1.
- Percentage of Subjects Achieving a Good or Moderate European League Against Rheumatism (EULAR) Response at Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
Good response is defined as:
DAS28[ESR] ≤ 3.2 and decrease from Baseline by > 1.2;
moderate response is defined as achievement of one of the following:
- DAS28[ESR] ≤ 3.2 and decrease from Baseline > 0.6 and ≤ 1.2
- DAS28[ESR] > 3.2 and ≤ 5.1 and decrease from Baseline > 0.6
- DAS28[ESR] > 5.1 and decrease from Baseline >1.2.
- Change From Baseline in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm) using the following formula:
0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x PtGADA, where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.
- Change From Baseline in Clinical Disease Activity Index (CDAI) to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
CDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), and Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm). 28 joints are examined where a lower score indicates less disease activity.
The CDAI score ranges from 0 to 76, with a negative value in CDAI change from Baseline indicating an improvement from Baseline.
- Change From Baseline in Simplified Disease Activity Index (SDAI) to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
SDAI is calculated as the sum of tender joint count (TJC), swollen joint count (SJC), Patient's Global Assessment of Disease Activity - Visual Analog Scale (PtGADA-VAS in mm), Physician's Global Assessment of Disease Activity - Visual Analog Scale (PhGADA-VAS in mm) and C-Reactive Protein (CRP in mg/L). 28 joints are examined where a lower score indicates less disease activity.
The SDAI score ranges from 0 to 86, with a negative value in SDAI change from Baseline indicating an improvement from Baseline.
- Percentage of Subjects With a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 52 [ Time Frame: Week 52 ]
Normative physical function is defined as HAQ-DI score ≤ 0.5. The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
The total score ranges from 0 to 3 with lower scores meaning lower disability.
- Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
The domains of the HAQ-DI are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.
The total score ranges from 0 (no difficulty) to 3 (unable to do) with lower scores meaning lower disability.
A negative value in HAQ-DI change from Baseline indicates an improvement from Baseline.
- Change From Baseline in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) Total Score to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ]
BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue).
A negative value in BRAF-MDQ change from Baseline indicates an improvement from Baseline.
- Number of Work Days Missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]Number of work days missed in the last month for employed subjects.
- Number of Work Days With Reduced Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]Number of work days with reduced productivity in the last month for employed subjects.
- Interference With Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]The Arthritis interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference) for employed subjects.
- Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]Number of days with no household work in the last month.
- Number of Days With Reduced Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]Number of days with reduced household work productivity in the last month.
- Number of Days With Hired Outside Help (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]Number of days with hired outside help in the last month.
- Number of Days Missed of Family/Social/Leisure Activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]Number of days missed of family/social/leisure activities in the last month.
- Interference With Household Work Productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ]The Arthritis interference in the last month with household work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference).
- Percentage of Subjects Achieving Low Disease Activity (LDA) at Week 52 [ Time Frame: Week 52 ]LDA is defined as achieving a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subjects must have a time since diagnosis of adult-onset Rheumatoid Arthritis (RA) less than 1 year as defined by the 2010 ACR/EULAR classification criteria from Screening Visit
- Positive Rheumatoid Factor (RF) and/or positive anticyclic Citrullinated Peptide Antibody (anti-CCP)
- Active RA disease
- DMARD-naïve
- Subject is naïve to RA related biologics
Exclusion Criteria:
- A diagnosis of any other inflammatory Arthritis
- History of infected joint prosthesis, or other significant infection and other serious medical condition
- Known Tuberculosis (TB) disease or high risk of acquiring TB infection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01519791
Show 178 study locations
| Study Director: | UCB Clinical Trial Call Center | +1 877 822 9493 (UCB) |
Publications of Results:
| Responsible Party: | UCB Pharma SA |
| ClinicalTrials.gov Identifier: | NCT01519791 |
| Other Study ID Numbers: |
RA0055 Period 1 2011-001729-25 ( EudraCT Number ) |
| First Posted: | January 27, 2012 Key Record Dates |
| Results First Posted: | September 22, 2015 |
| Last Update Posted: | July 31, 2018 |
| Last Verified: | March 2018 |
|
Certolizumab Pegol - Cimzia Methotrexate Rheumatoid Arthritis |
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Certolizumab Pegol Methotrexate Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs |
Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Tumor Necrosis Factor Inhibitors Anti-Inflammatory Agents |