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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT01521923
First received: January 19, 2012
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

This study is intended to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in combination with Methotrexate (MTX) for sustaining clinical response achieved in study RA0055A. Subjects entering this study RA0055B achieved sustained Low Disease Activity at Week 52 in study RA0055A.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: Certolizumab Pegol + Methotrexate (MTX)
Biological: Placebo + Methotrexate (MTX)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • Percentage of subjects with Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 in RA0055B without flaring [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    This Outcome Measure includes all subjects that have a DAS28 [ESR] ≤ 3.2 from the start of RA0055B (Week 52 of RA0055A) to Week 104 in RA0055B without flaring.


Secondary Outcome Measures:
  • Percentage of subjects with Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) < 2.6 at Week 52 in previous study RA0055A who maintain a DAS28 [ESR] < 2.6 from Week 52 in RA0055A through Week 104 in RA0055B without flaring [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Baseline in previous study RA0055A in modified Total Sharp Score (mTSS) to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Van der Heijde modified Total Sharp Score (mTSS).

  • Change from Week 52 in previous study RA0055A in modified Total Sharp Score (mTSS) to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Van der Heijde modified Total Sharp Score (mTSS).

  • Percentage of subjects with radiographic non-progression from Baseline in previous study RA0055A to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Radiographic nonprogression is defined as change in modified Total Sharp Score (mTSS) ≤ 0.5.

  • Percentage of subjects with radiographic non-progression from Week 52 in previous study RA0055A to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Radiographic nonprogression is defined as change in modified Total Sharp Score (mTSS) ≤ 0.5.

  • Change from Baseline in previous study RA0055A in the joint erosion score to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Week 52 in previous study RA0055A in the joint erosion score to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Baseline in previous study RA0055A in the joint narrowing score to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Week 52 in previous study RA0055A in the joint narrowing score to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Percentage of subjects meeting the American College of Rheumatology 20% response criteria (ACR20) at Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    The assessments are based on a 20% or greater improvement from Baseline in previous study RA0055A 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 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    The assessments are based on a 50% or greater improvement from Baseline in previous study RA0055A 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 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    The assessments are based on a 70% or greater improvement from Baseline in previous study RA0055A 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 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]

    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 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Percentage of subjects with Simplified Disease Activity Index (SDAI) ≤ 3.3 at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Percentage of subjects with Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Percentage of subjects meeting the 2011 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) remission criteria simplified for clinical practice at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]

    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 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]

    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 previous study RA0055A in Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Week 52 in previous study RA0055A in Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Baseline in previous study RA0055A in Clinical Disease Activity Index (CDAI) to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Week 52 in previous study RA0055A in Clinical Disease Activity Index (CDAI) to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Baseline in previous study RA0055A in Simplified Disease Activity Index (SDAI) to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Change from Week 52 in previous study RA0055A in Simplified Disease Activity Index (SDAI) to Week 104 in RA0055B [ Time Frame: From Week 52 in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Percentage of subjects with a Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5 at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Percentage of subjects with Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2 at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
  • Time to flare from Week 52 in RA0055A to Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Time to flare, defined as an increase of DAS28[ESR] ≥ 0.6 above Week 52 DAS28[ESR] level, having a DAS28[ESR] ≥ 3.2 and judged by the Investigator as due to RA and all three criteria confirmed at an additional visit two weeks thereafter, from Week 52 onwards.

  • Change from Baseline in previous study RA0055A in the Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ) total score to Week 104 in RA0055B [ Time Frame: From Baseline (Week 0) in RA0055A to Week 104 in RA0055B ] [ Designated as safety issue: No ]
    BRAF-MDQ total score ranges from 0 to 70 (with higher scores indicating worse fatigue), whereas the score for each dimension is different due to the varied number of questions (0 -22 for physical, 0- 21 for living, 0- 15 for cognition, and 0- 12 for emotion).

  • Number of work days missed (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Number of work days missed in the last month.

  • Number of work days with reduced productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Number of work days with reduced productivity in the last month.

  • Interference with work productivity (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    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).

  • Number of days with no household work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    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 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    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 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    Number of days with hired outside help days in the last month.

  • Number of days missed of family/social/leisure activities (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    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 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    The Arthritis interference in the last month with household 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 104 in RA0055B [ Time Frame: Week 104 in RA0055B ] [ Designated as safety issue: No ]
    LDA is defined as achieving a Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) ≤ 3.2.


Enrollment: 880
Study Start Date: January 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CZP 200 mg Q2W + Methotrexate Biological: Certolizumab Pegol + Methotrexate (MTX)

Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at dosage strength of 200 mg/ml.

On a maintenance dose of 200 mg every 2 Weeks (Q2W) until Week 102. On a maintenance dose of 200 mg every 4 Weeks (Q4W) until Week 102/ Placebo (PBO) 1 syringe every 4 Weeks (Q4W).

CZP and PBO administration to be staggered 2 Weeks apart to maintain blind.

The MTX treatment is to remain between 15-25 mg/week.

Other Names:
  • Cimzia
  • CZP
  • MTX
Experimental: CZP 200 mg Q4W + Methotrexate Biological: Certolizumab Pegol + Methotrexate (MTX)

Prefilled syringes containing an injectable volume of 1 ml of solution for injection CZP for single use at dosage strength of 200 mg/ml.

On a maintenance dose of 200 mg every 2 Weeks (Q2W) until Week 102. On a maintenance dose of 200 mg every 4 Weeks (Q4W) until Week 102/ Placebo (PBO) 1 syringe every 4 Weeks (Q4W).

CZP and PBO administration to be staggered 2 Weeks apart to maintain blind.

The MTX treatment is to remain between 15-25 mg/week.

Other Names:
  • Cimzia
  • CZP
  • MTX
Placebo Comparator: Placebo + Methotrexate Biological: Placebo + Methotrexate (MTX)

1 syringe of Placebo every 2 Weeks and MTX.

The MTX treatment is to remain between 15-25 mg/week.

Other Name: MTX

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Those subjects in previous study RA0055A who are in sustained LDA (defined as DAS28[ESR] ≤ 3.2 at Weeks 40 and 52) at Week 52 in previous study RA0055A

Exclusion Criteria:

- Those subjects in previous study RA0055A who are NOT in sustained LDA (defined as DAS28[ESR] ≤ 3.2 at Weeks 40 and 52) at Week 52 in previous study RA0055A

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01521923

  Show 178 Study Locations
Sponsors and Collaborators
UCB, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT01521923     History of Changes
Other Study ID Numbers: RA0055B, 2011-001729-25
Study First Received: January 19, 2012
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Mexico: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by UCB, Inc.:
Certolizumab Pegol - Cimzia
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Methotrexate
Certolizumab pegol
Immunoglobulin Fab Fragments
Therapeutic Uses
Pharmacologic Actions
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
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 01, 2014