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 is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc. ( UCB Pharma SA )
ClinicalTrials.gov Identifier:
NCT01500278
First received: December 22, 2011
Last updated: March 27, 2014
Last verified: March 2014
  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

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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: February 2016
Estimated 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 + 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:
  • Cimzia
  • CZP
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:
  • Humira
  • ADA
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:
  • Cimzia
  • CZP
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:
  • Humira
  • ADA
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:
  • Cimzia
  • CZP
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:
  • Humira
  • ADA

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  • 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:

    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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01500278

  Show 151 Study Locations
Sponsors and Collaborators
UCB Pharma SA
Investigators
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: March 27, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Austrian Medicines and Medical Devices Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Paul-Ehrlich-Institut
Greece: National Organization of Medicines
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Protection Against Health Risks
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Agency for Medicines and Medical Devices
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
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 April 17, 2014