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An Observational Study of MabThera in Participants With Severe Active Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01613027
First received: May 25, 2012
Last updated: August 31, 2016
Last verified: August 2016
  Purpose
This observational study will evaluate the effect on disease activity and the safety in routine clinical practice of MabThera (rituximab) in participants with active seropositive rheumatoid arthritis, who have an inadequate response to one or more tumour necrosis factor inhibitor (anti-TNF) therapies.

Condition Intervention
Rheumatoid Arthritis
Biological: Rituximab

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multicenter Observational Study of the Response to Rituximab (MabThera®) in Seropositive Patients With Rheumatoid Arthritis With Inadequate Response or Intolerance to Treatment With One or More Tumor Necrosis Factor Inhibitors (TNFi)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change From Baseline in Disease Activity Score Based on 28-joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Month 6 and Month 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    DAS28-ESR is a measure of the participant's disease activity and was calculated using the swollen joint count of 28 joints (SJC28), tender joint count of 28 joints (TJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment of disease activity (100-millimeter [mm] horizontal visual analog scale with 0=no disease activity to 100=maximum disease activity). DAS28-ESR scores range from 0 to 10, with higher scores corresponding to greater disease activity.


Secondary Outcome Measures:
  • Percentage of Participants With European League Against Rheumatism (EULAR) Response at Month 6 and Month 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    EULAR response was calculated as the difference between DAS28-ESR scores at baseline and Month 6, and baseline and Month 12, and reported as the percentage of participants with response overall, good response, moderate response, and no response measured at each time point. Good responders = decrease from baseline >1.2 with a DAS28 score of ≤3.2; moderate responders = decrease from baseline >1.2 with a DAS28 score of >3.2, or decrease from baseline >0.6 to ≤1.2 with a DAS28 score of ≤5.1; non-responders = decrease from baseline ≤0.6 or decrease from baseline >0.6 and ≤1.2 with a DAS28 score of >5.1.

  • Change From Baseline in Swollen Joint Count (SJC) at Month 6 and Month 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    SJC was determined by examining 28 and 66 joints and identifying when swelling was present. Swelling was recorded on the joint assessment form at baseline, no swelling = 0, swelling =1. The sum of swollen joints, each, ranged from 0 to 28 with 0 as best possible health status and 28 as worst health status. A decrease from baseline indicates improvement.

  • Change From Baseline in Tender Joint Count (TJC) at Month 6 and Month 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    TJC was determined by examining 28 and 68 joints and identifying the joints that were painful under pressure or to passive motion. Tenderness was recorded on the joint assessment form at baseline, no tenderness = 0, tenderness = 1. A decrease from baseline indicates improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Month 6 and Month 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    ESR is an direct measure of how much inflammation is in the body. The normal range is 0-22 mm/hour for men and 0-29 mm/hour for women. A decrease from baseline indicates improvement.

  • Change From Baseline in C-reactive Protein (CRP) at Month 6 and Month 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    C-reactive protein (CRP) is a blood test marker for inflammation in the body. Normal CRP levels are below 5.0 milligrams per liter (mg/L). A decrease from baseline indicates improvement.

  • Percentage of Participants Who Remained on Treatment or Discontinued Treatment by Month 6 and Month 12 [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Reasons for Discontinuation of Treatment by Month 6 [ Time Frame: Baseline to Month 6 ] [ Designated as safety issue: No ]
    Reasons for discontinuation from baseline to Month 6 are presented as the number of participants who discontinued treatment by category of reason for discontinuation.

  • Reasons for Discontinuation of Treatment by Month 12 [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    Reasons for discontinuation from baseline to Month 12 are presented as the number of participants who discontinued treatment by category of reason for discontinuation.

  • Percentage of Participants With Clinically Meaningful Improvement From Baseline in Modified Health Assessment Questionnaire (M-HAQ) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

    The M-HAQ is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. A negative change from baseline indicates improvement.

    Clinically meaningful improvement was defined as minimum clinically significant reduction from baseline of ≥0.22 at the respective time point.


  • Percentage of Participants With Adverse Events (AEs) and Adverse Drug Reactions (ADRs) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An ADR was defined as any noxious and unintended response to a medicinal product related to any dose. AEs of special interest includes progressive multifocal leukoencephalopathy (PML), any encephalopathy, hepatitis B or hepatitis B reactivation, gastrointestinal perforation, tuberculosis (TB) or TB reactivation, opportunistic infections, and malignancies.

  • Percentage of Participants With Any Non-Serious AE and Any Serious AE by Intensity [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

    Percentage of participants with any non-serious AE and any serious AE by intensity (mild, moderate, severe) was reported.

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.


  • Percentage of Non-Serious AEs [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

    Percentage of non-serious AEs resolved and ongoing at the time of study completion were reported.

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.


  • Percentage of Non-Serious ADRs [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

    Percentage of non-serious ADRs at the time of study completion was reported.

    An ADR was defined as any noxious and unintended response to a medicinal product related to any dose.


  • Percentage of Serious AEs [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

    Percentage of serious AEs resolved and ongoing at the time of study completion was reported.

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.


  • Percentage of Serious ADRs [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

    Percentage of serious ADRs resolved and ongoing at the time of study completion was reported.

    An ADR was defined as any noxious and unintended response to a medicinal product related to any dose.



Enrollment: 135
Study Start Date: February 2012
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Rituximab
Rituximab administered according to prescribing information and normal clinical practice.
Biological: Rituximab
Rituximab administered according to prescribing information and normal clinical practice.
Other Name: MabThera®

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants with severe active, seropositive rheumatoid arthritis who have an inadequate response or intolerance to anti-TNF therapy
Criteria

Inclusion Criteria:

  • Age >18 years with rheumatoid arthritis (RA)
  • Seropositive participants with RA (positive for rheumatoid factor (RF) and/or anti-Citrullinated Cyclic Peptide [CCP])
  • Active disease despite receiving one or more TNF inhibitors
  • Absence of serious or active infection

Exclusion Criteria:

  • Participants with serious history of heart failure (class New York Heart Association [NYHA] IV) or severe uncontrolled heart disease
  • Participants pregnant or lactating
  • Prior treatment with Mabthera®
  • Participants receiving any other investigational product in the context of other clinical study
  • Participants with known hypersensitivity to rituximab or to any of the excipients
  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: NCT01613027

Locations
Greece
Athens, Greece, 11521
Athens, Greece, 11527
Athens, Greece, 14527
Athens, Greece, 155 62
Haidari, Greece, 124 62
Herakleion, Greece, 71110
Ioannina, Greece, 455 00
Larissa, Greece, 411 10
Patras, Greece, 265 04
Patra, Greece, 26335
Thessaloniki, Greece, 544 65
Thessaloniki, Greece, 546 42
Thessaloniki, Greece, 57010
Voula, Greece, 16673
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01613027     History of Changes
Other Study ID Numbers: ML27998 
Study First Received: May 25, 2012
Results First Received: August 31, 2016
Last Updated: August 31, 2016
Health Authority: Greece: Ministry of Health and Welfare

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 02, 2016