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 has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )
ClinicalTrials.gov Identifier:
NCT01519791
First received: January 19, 2012
Last updated: January 20, 2016
Last verified: January 2016
  Purpose
This study is intended to evaluate the efficacy and safety of Certolizumab Pegol (CZP) in combination with Methotrexate (MTX) for inducing and sustaining clinical response in the treatment of Disease Modifying Antirheumatic Drug (DMARD)-naïve adults with early active Rheumatoid Arthritis.

Condition Intervention Phase
Rheumatoid Arthritis
Biological: Certolizumab Pegol
Other: Placebo
Biological: Methotrexate
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 Pharma:

Primary Outcome Measures:
  • Percentage of Subjects in Sustained Remission at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Percentage of Subjects in Sustained Low Disease Activity (LDA) at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ 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 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ 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 52 [ Time Frame: From Baseline (Week 0) to Week 52 ] [ 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 Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28 [ESR]) to Week 52 [ Time Frame: From Baseline (Week 0) to Week 52 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ 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) for employed subjects.

  • Number of Days With no Household Work (Work Productivity Survey - Rheumatoid Arthritis [WPS-RA]) at Week 52 [ Time Frame: Week 52 ] [ 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 52 [ Time Frame: Week 52 ] [ 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 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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 ] [ 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 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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 ] [ 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
Study Completion Date: September 2015
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Cimzia
  • CZP
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01519791

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

Additional Information:
Responsible Party: UCB Pharma SA
ClinicalTrials.gov Identifier: NCT01519791     History of Changes
Other Study ID Numbers: RA0055 Period 1  2011-001729-25 
Study First Received: January 19, 2012
Results First Received: July 8, 2015
Last Updated: January 20, 2016
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: Agence Nationale de Sécurité du Médicament et des produits de santé
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 Pharma:
Certolizumab Pegol - Cimzia
Methotrexate
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Certolizumab Pegol
Antirheumatic Agents
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 July 26, 2016