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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01500278
First Posted: December 28, 2011
Last Update Posted: August 8, 2017
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.
Collaborator:
Parexel
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )
  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 (CZP) Biological: Adalimumab (ADA) Drug: Methotrexate (MTX) Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (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

Resource links provided by NLM:


Further study details as provided by UCB Pharma ( UCB Pharma SA ):

Primary Outcome Measures:
  • Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 12 [ Time Frame: Week 12 ]
    Subjects who met the ACR20 criteria were 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 Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 [ Time Frame: Week 104 ]
    DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.


Secondary Outcome Measures:
  • Percentage of Week 12 Responders Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 [ Time Frame: Week 104 ]

    DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.

    The definition of Week 12 responders was DAS28[ESR] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28[ESR] relative to Baseline.


  • Percentage of Subjects Who Met the American College of Rheumatology 20 % (ACR20) Criteria at Week 6 [ Time Frame: Week 6 ]
    Subjects who met the ACR20 criteria were 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 Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 6 [ Time Frame: Week 6 ]
    DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.

  • Percentage of Subjects Who Had a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 [ Time Frame: Week 12 ]
    DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were 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 ]

    DAS28 [ESR] was 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 Patient Global Assessment of Arthritis, where 28 joints were examined and a lower score indicates less disease activity.

    The definition of Week 6/12 responders was DAS28[ESR] Low Disease Activity (LDA) (ie ≤ 3.2) or an improvement of ≥ 1.2 in DAS28[ESR] relative to Baseline.


  • Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 104 [ Time Frame: From Baseline to Week 104 ]
    HAQ-DI was derived based on the mean of individual scores in 8 categories of daily living actives (using 20 questions). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), and the total HAQ-DI was scored on the scale of 0-3 as well. Change from Baseline was computed as the value at Week 104 minus the Baseline value. A negative value in Change from Baseline indicates an improvement.

  • Kaplan-Meier Estimates of Proportion of Subjects Who Discontinued After Response at Week 12 [ Time Frame: From Week 12 up to Week 104 ]
    Response at Week 12 means that a subject had either a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 12 or had a reduction of DAS28 [ESR] ≥ 1.2 from Baseline to Week 12. Kaplan-Meier Estimates of Proportion of Subjects Discontinued are presented per study week (days relative to Week 12 visit).


Enrollment: 915
Study Start Date: December 2011
Study Completion Date: January 2016
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Certolizumab Pegol + Methotrexate (CZP + MTX) Biological: Certolizumab Pegol (CZP)
  • Active substance: an injectable volume of 1 ml solution for injection CZP
  • Pharmaceutical form: prefilled syringes CZP
  • Concentration: 200 mg/ml CZP
  • Route of Administration: injections will be given subcutaneously: loading dose of 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.
Other Names:
  • Cimzia
  • CZP
Drug: Methotrexate (MTX)
  • Active substance: Methotrexate
  • Pharmaceutical form: oral tablet
  • Concentration: 15-25 mg/week
  • Route of Administration: MTX orally
Other Name: MTX
Active Comparator: Adalimumab + Methotrexate (ADA + MTX) Biological: Adalimumab (ADA)
  • Active substance: an injectable volume of 0.8 ml solution for injection ADA
  • Pharmaceutical form: prefilled syringes ADA
  • Concentration: 40 mg/0.8 ml ADA
  • Route of Administration: 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.
Other Names:
  • Humira
  • ADA
Drug: Methotrexate (MTX)
  • Active substance: Methotrexate
  • Pharmaceutical form: oral tablet
  • Concentration: 15-25 mg/week
  • Route of Administration: MTX orally
Other Name: MTX
Active Comparator: CZP + MTX followed by ADA + MTX
Those subjects who received Certolizumab Pegol (400 mg at Weeks 0, 2, 4 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) at Baseline and are Non-Responders at Week 12, switch to Adalimumab (40 mg) + Methotrexate (ADA + MTX) after Week 12.
Biological: Certolizumab Pegol (CZP)
  • Active substance: an injectable volume of 1 ml solution for injection CZP
  • Pharmaceutical form: prefilled syringes CZP
  • Concentration: 200 mg/ml CZP
  • Route of Administration: injections will be given subcutaneously: loading dose of 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.
Other Names:
  • Cimzia
  • CZP
Biological: Adalimumab (ADA)
  • Active substance: an injectable volume of 0.8 ml solution for injection ADA
  • Pharmaceutical form: prefilled syringes ADA
  • Concentration: 40 mg/0.8 ml ADA
  • Route of Administration: 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.
Other Names:
  • Humira
  • ADA
Drug: Methotrexate (MTX)
  • Active substance: Methotrexate
  • Pharmaceutical form: oral tablet
  • Concentration: 15-25 mg/week
  • Route of Administration: MTX orally
Other Name: MTX
Active Comparator: ADA + MTX followed by CZP + MTX
Those subjects who received Adalimumab (40 mg + Placebo at Weeks 0, 2, 4 followed by 40 mg ADA every two weeks) + Methotrexate (ADA+ MTX) at Baseline and are Non-Responders at Week 12, switch to Certolizumab Pegol (400 mg at Weeks 12, 14, 16 followed by 200 mg every two weeks) + Methotrexate (CZP+ MTX) after Week 12.
Biological: Certolizumab Pegol (CZP)
  • Active substance: an injectable volume of 1 ml solution for injection CZP
  • Pharmaceutical form: prefilled syringes CZP
  • Concentration: 200 mg/ml CZP
  • Route of Administration: injections will be given subcutaneously: loading dose of 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.
Other Names:
  • Cimzia
  • CZP
Biological: Adalimumab (ADA)
  • Active substance: an injectable volume of 0.8 ml solution for injection ADA
  • Pharmaceutical form: prefilled syringes ADA
  • Concentration: 40 mg/0.8 ml ADA
  • Route of Administration: 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.
Other Names:
  • Humira
  • ADA
Drug: Methotrexate (MTX)
  • Active substance: Methotrexate
  • Pharmaceutical form: oral tablet
  • Concentration: 15-25 mg/week
  • Route of Administration: MTX orally
Other Name: MTX

  Eligibility

Information from the National Library of Medicine

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, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (Aletaha D et al, 2010)
  • Subject must have a positive Rheumatoid Factor (RF) and/or a positive anti-Cyclic Citrullinated Peptide antibody (anti-CCP) as determined by the central laboratory at Screening
  • Subject must have moderate to severe RA disease at Screening and Baseline defined as:

    1. 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
    2. 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 Screening and has used the same MTX regimen for a minimum of 28 days prior to Baseline

Exclusion Criteria:

  • Subject has previously received any biological Disease Modifying Antirheumatic Drug (DMARD) or has received treatment with cyclophosphamide, chlorambucil, Janus Kinase, phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase
  • Diagnosis of any other inflammatory arthritis
  • Infected with Tuberculosis (TB) or high risk of acquiring TB infection
  • Subjects with concurrent acute or chronic viral hepatitis B or C infection
  • Subjects with a history of chronic or recurrent infections or subjects at high risk of infection
  • Use of prohibited medications like nonbiological DMARDs (excluding MTX), biological DMARDs excluding study medications, experimental therapy, IA hyaluronic acid
  Contacts and Locations
Information from the National Library of Medicine

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): NCT01500278


  Show 175 Study Locations
Sponsors and Collaborators
UCB Pharma SA
Parexel
Investigators
Study Director: UCB Cares +1 877 822 9493 (UCB)
  More Information

Additional Information:
Publications:
Responsible Party: UCB Pharma SA
ClinicalTrials.gov Identifier: NCT01500278     History of Changes
Other Study ID Numbers: RA0077
2011-002067-20 ( EudraCT Number )
First Submitted: December 22, 2011
First Posted: December 28, 2011
Results First Submitted: November 22, 2016
Results First Posted: March 31, 2017
Last Update Posted: August 8, 2017
Last Verified: July 2017

Keywords provided by UCB Pharma ( UCB Pharma SA ):
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
Certolizumab Pegol
Adalimumab
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
Anti-Inflammatory Agents


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