Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis (RA) Inadequately Responding to Methotrexate
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Purpose
This study is conducted to evaluate the short (12 Weeks) and long term (104 Weeks) efficacy of Certolizumab Pegol compared with Adalimumab both in combination with Methotrexate (MTX) in the treatment of moderate to severe Rheumatoid Arthritis (RA) that is not responding adequately to MTX.
| Condition | Intervention | Phase |
|---|---|---|
|
Rheumatoid Arthritis |
Biological: Certolizumab Pegol + Methotrexate (CZP + MTX) Biological: Adalimumab + Methotrexate (ADA + MTX) |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Multicenter, Single-blind, Randomized Parallel-group Study to Assess the Short- and Long-term Efficacy of Certolizumab Pegol Plus Methotrexate Compared to Adalimumab Plus Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis Responding Inadequately to Methotrexate |
- Percentage of subjects who meet the American College of Rheumatology 20 % (ACR20) criteria at Week 12 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]Subjects who meet the ACR20 criteria are those 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).
- Percentage of subjects who have a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]DAS28 [ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), ESR (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 Patient Global Assessment of Arthritis, where 28 joints are examined and a lower score indicates less disease activity.
- Percentage of Week 12 responders who have a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
DAS28 [ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), ESR (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 Patient Global Assessment of Arthritis, where 28 joints are examined and a lower score indicates less disease activity.
Week 12 responders are those subjects who have either a DAS28 [ESR] ≤ 3.2 at Week 12 or have a reduction of DAS28 [ESR] ≥ 1.2 from Baseline to Week 12.
- Percentage of subjects who meet the American College of Rheumatology 20 % (ACR20) criteria at Week 6 [ Time Frame: From Baseline to Week 6 ] [ Designated as safety issue: No ]Subjects who meet the ACR20 criteria are those 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).
- Percentage of subjects who have a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]DAS28 [ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), ESR (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 Patient Global Assessment of Arthritis, where 28 joints are examined and a lower score indicates less disease activity.
- Percentage of subjects who have a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]DAS28 [ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), ESR (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 Patient Global Assessment of Arthritis, where 28 joints are examined and a lower score indicates less disease activity.
- Percentage of subjects with a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104, in subjects responding at both Week 6 and Week 12 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
DAS28 [ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC), ESR (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 Patient Global Assessment of Arthritis, where 28 joints are examined and a lower score indicates less disease activity.
Week 6 and Week 12 responders are those subjects who have either a DAS28 [ESR] ≤ 3.2 at Week 6 and 12 or have a reduction of DAS28 [ESR] ≥ 1.2 from Baseline to Week 6 and 12.
- Change from Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104 [ Time Frame: From Baseline to Week 104 ] [ Designated as safety issue: No ]HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). Change from Baseline is computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement.
- Time to all-cause study discontinuation, defined as the number of days from response at Week 12 until completion at Week 104 or withdrawal before Week 104 [ Time Frame: From Week 12 up to Week 104 ] [ Designated as safety issue: No ]Response at Week 12 means that a subject has either a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 or has a reduction of DAS28 [ESR] ≥ 1.2 from Baseline to Week 12.
| Estimated Enrollment: | 892 |
| Study Start Date: | December 2011 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | January 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: Certolizumab Pegol + Methotrexate (CZP + MTX) |
Biological: Certolizumab Pegol + Methotrexate (CZP + MTX)
Prefilled syringes containing an injectable volume of 1 ml solution for injection CZP for single use at dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal. Subjects must be taking MTX 15 to 25 mg/week orally or subcutaneously and maintain the same route of administration from Baseline through Week 104. For subjects who cannot tolerate MTX at doses between 15 to 25 mg/week, the dose may be reduced to 10 mg/week orally or subcutaneously. Other Names:
|
| Active Comparator: Adalimumab + Methotrexate (ADA + MTX) |
Biological: Adalimumab + Methotrexate (ADA + MTX)
Prefilled syringes containing an injectable volume of 0.8 ml solution for injection ADA for single use at dosage strength of 40 mg/0.8 ml. Injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal. Subjects must be on MTX 15 to 25 mg/week orally or subcutaneously and maintain the same route of administration from Baseline through Week 104. For subjects who cannot tolerate MTX at doses between 15 to 25 mg/week, the dose may be reduced to 10 mg/week orally or subcutaneously. Other Names:
|
|
Active Comparator: CZP + MTX followed by ADA + MTX
Those subjects who received Certolizumab Pegol + Methotrexate (CZP + MTX) at Baseline and are Non-Responders at Week 12 switch to Adalimumab + Methotrexate (ADA + MTX) after Week 12
|
Biological: Certolizumab Pegol + Methotrexate (CZP + MTX)
Prefilled syringes containing an injectable volume of 1 ml solution for injection CZP for single use at dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal. Subjects must be taking MTX 15 to 25 mg/week orally or subcutaneously and maintain the same route of administration from Baseline through Week 104. For subjects who cannot tolerate MTX at doses between 15 to 25 mg/week, the dose may be reduced to 10 mg/week orally or subcutaneously. Other Names:
Biological: Adalimumab + Methotrexate (ADA + MTX)
Prefilled syringes containing an injectable volume of 0.8 ml solution for injection ADA for single use at dosage strength of 40 mg/0.8 ml. Injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal. Subjects must be on MTX 15 to 25 mg/week orally or subcutaneously and maintain the same route of administration from Baseline through Week 104. For subjects who cannot tolerate MTX at doses between 15 to 25 mg/week, the dose may be reduced to 10 mg/week orally or subcutaneously. Other Names:
|
|
Active Comparator: ADA + MTX followed by CZP + MTX
Those subjects who received Adalimumab + Methotrexate (ADA + MTX) at Baseline and are Non-Responders at Week 12 switch to Certolizumab Pegol + Methotrexate (CZP + MTX) after Week 12
|
Biological: Certolizumab Pegol + Methotrexate (CZP + MTX)
Prefilled syringes containing an injectable volume of 1 ml solution for injection CZP for single use at dosage strength of 200 mg/ml. Injections will be given subcutaneously. CZP 400 mg at Baseline, and Weeks 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks through Week 102 or withdrawal. Subjects must be taking MTX 15 to 25 mg/week orally or subcutaneously and maintain the same route of administration from Baseline through Week 104. For subjects who cannot tolerate MTX at doses between 15 to 25 mg/week, the dose may be reduced to 10 mg/week orally or subcutaneously. Other Names:
Biological: Adalimumab + Methotrexate (ADA + MTX)
Prefilled syringes containing an injectable volume of 0.8 ml solution for injection ADA for single use at dosage strength of 40 mg/0.8 ml. Injections will be given subcutaneously. ADA 40 mg plus an injection with Placebo (to preserve blind) at Baseline, and Weeks 2 and 4, followed by ADA 40 mg every 2 weeks through Week 102 or withdrawal. Subjects must be on MTX 15 to 25 mg/week orally or subcutaneously and maintain the same route of administration from Baseline through Week 104. For subjects who cannot tolerate MTX at doses between 15 to 25 mg/week, the dose may be reduced to 10 mg/week orally or subcutaneously. Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subject must have a diagnosis of Rheumatoid Arthritis (RA) at Screening, as defined by the 2010 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria
- Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti Cyclic Citrullinated Peptide antibody (anti-CCP) at Screening
Subject must have moderate to severe RA disease at Screening and Baseline defined as:
Screening (all criteria required)
- ≥ 4 swollen joints (of 28 prespecified joints)
- Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2
- C-Reactive Protein (CRP) concentration ≥ 10 mg/L (or 1.0 mg/dL) or Erythrocyte Sedimentation Rate (ESR) (Westergren) ≥ 28 mm/hr
Baseline (both criteria required)
- ≥ 4 swollen joints (of 28 prespecified joints)
- Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) > 3.2
- Subject must have inadequately responded previously to Methotrexate (MTX)
- Subject is using MTX 15 to 25 mg/week orally or subcutaneously at Baseline
Exclusion Criteria:
- Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD)
- Diagnosis of any other inflammatory arthritis
- Infected with Tuberculosis (TB) or high risk of acquiring TB infection
Contacts and Locations| Contact: UCB Clinical Trial Call Center | +1 877 822 9493 |
Show 159 Study Locations| Study Director: | UCB Clinical Trial Call Center | +1 877 822 9493 (UCB) |
More Information
No publications provided
| Responsible Party: | UCB, Inc. ( UCB Pharma SA ) |
| ClinicalTrials.gov Identifier: | NCT01500278 History of Changes |
| Other Study ID Numbers: | RA0077, 2011-002067-20 |
| Study First Received: | December 22, 2011 |
| Last Updated: | May 16, 2013 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration Czech Republic: State Institute for Drug Control Germany: Paul-Ehrlich-Institut Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines Hungary: National Institute of Pharmacy United States: Food and Drug Administration |
Keywords provided by UCB, Inc.:
|
Certolizumab Pegol Cimzia Adalimumab Humira Rheumatoid Arthritis |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Methotrexate Adalimumab Immunoglobulin Fab Fragments Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs |
Pharmacologic Actions Therapeutic Uses 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 Anti-Inflammatory Agents |
ClinicalTrials.gov processed this record on May 16, 2013