Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Observational Study of MabThera/Rituxan (Rituximab) and Alternative TNF-Inhibitors in Patients With Rheumatoid Arthritis and an Inadequate Response to a Single Previous TNF-Inhibitor

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.
 
ClinicalTrials.gov Identifier: NCT01557348
Recruitment Status : Completed
First Posted : March 19, 2012
Results First Posted : January 24, 2017
Last Update Posted : January 24, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date March 13, 2012
First Posted Date March 19, 2012
Results First Submitted Date November 28, 2016
Results First Posted Date January 24, 2017
Last Update Posted Date January 24, 2017
Study Start Date June 2009
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 28, 2016)
Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month 6 [ Time Frame: Baseline (Day of change in biologic therapy [<=Day 1]) and Month 6 ]
The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour [mm/hr]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
Original Primary Outcome Measures
 (submitted: March 16, 2012)
Mean change in Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) 6 months after change in biologic therapy [ Time Frame: approximately 14 years ]
Change History Complete list of historical versions of study NCT01557348 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: November 28, 2016)
  • Least Squares Mean Change From Baseline in Disease Activity Score (3 Variables)-Erythrocyte Sedimentation Rate at Month12 [ Time Frame: Baseline (Day of change in biologic therapy [<=Day 1]) and Month 12 ]
    The DAS28-3 (ESR) is a measure of disease activity in rheumatoid arthritis. It is calculated from the number of swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, and ESR (millimeters per hour [mm/hr]). Total score ranges from 0 to 9.4, where higher score indicated more disease activity. Decrease in score indicated improvement in disease activity.
  • Least Squares Mean Change From Baseline in TJC at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    The TJC is the most specific clinical method to quantify abnormalities in participants with rheumatoid arthritis (RA). A total of 28 joints were assessed for tenderness. Decrease in score indicated an improvement in disease activity.
  • Least Squares Mean Change From Baseline in SJC at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    The SJC is the most specific clinical method to quantify abnormalities in participants with RA. A total of 28 joints were assessed for swelling. Decrease in the score indicated improvement in disease activity.
  • Least Squares Mean Change From Baseline in C-reactive Protein at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    C-reactive protein (CRP) is an inflammation marker. Normal range is from 0-10 milligram/Liter. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in disease activity.
  • Least Squares Mean Change From Baseline in ESR at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    The ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells sediment in a period of one hour. Normal range is 0-30 mm/hr. A reduction in the level of ESR is considered as an improvement in disease activity.
  • Least Squares Mean Change From Baseline in Physician Global Assessment of Disease at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    Physician global assessment of disease was measured on a 0 to 100 millimeter (mm) visual analog scale (VAS), with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
  • Least Squares Mean Change From Baseline in Patient Global Assessment of Disease at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    Patient Global Assessment of Disease was measured on a 0 to 100 mm VAS, with 0 mm = no disease activity and 100 mm = highest possible disease activity. Higher scores indicate worsening of disease.
  • Least Squares Mean Change From Baseline in Participant's VAS Pain Score at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    Participants were asked to assess their pain intensity (severity of pain) on a 100-millimeter (mm) VAS with the left edge (0 mm) defined as "no pain" and the right edge (100 mm) defined as "severest pain". Higher scores indicate worsening of disease.
  • Least Squares Mean Change From Baseline in Health Assessment Questionnaire-Disability Index at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    Health Assessment Questionnaire-Disability Index (HAQ-DI) is participant reported assessment of ability to perform tasks in 8 categories of daily living activities as dress/groom, arise, eat, walk, reach, grip, hygiene, and common activities over past week. Each item was scored on a 4-point scale from 0 to 3, where 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. Overall score was computed as the sum of domain scores divided by the number of domains answered. Total possible score range was 0-3, where 0 = least difficulty and 3 = extreme difficulty.
  • Least Squares Mean Change From Baseline in Duration of Morning Stiffness at Months 6 and 12 [ Time Frame: Baseline, Month 6, and Month 12 ]
    Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes. Participants with available data at the time of assessment were included in the analysis.
  • Percentage of Participants Who Remained on Their Second Biologic Therapy at Months 6 and 12 After Start of Second Biologic Therapy [ Time Frame: Month 6 and Month 12 ]
    Percentage of participants who remained on their second biologic therapy at 6 and 12 months after start of second biologic therapy were reported.
  • Reasons for Stopping the Second Biologic Therapy and Subsequent Therapy Choice [ Time Frame: Up to 12 months ]
  • Number of Participants With Any Adverse Events, Any Serious Adverse Event, Adverse Events Leading to Withdrawal, and Death [ Time Frame: Up to 12 Months ]
    An Adverse event is defined as any unfavorable and unintended medical occurrence/sign (including an abnormal laboratory finding), symptom or disease in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is medically significant or requires intervention to prevent one or other of the outcomes listed above.
  • Number of Participants With Reasons for Discontinuation of the First TNFi Therapy [ Time Frame: Day 1 (Study entry visit) ]
    The reasons for discontinuation of first TNFi therapy included inefficacy, intolerance and other reasons. The other reasons included complete remission and participants' non-compliance.
  • Number of Participants With Previous TNFi Therapy [ Time Frame: Day 1 (Study entry visit) ]
    The previous TNFi therapy included adalimumab, etanercept, infliximab, and others (certolizumab, and golimumab). Number of participants with previous TNFi therapy history was reported.
  • Number of Participants With Previous Non-biologic Disease-modifying Anti-rheumatic Drugs Therapy [ Time Frame: Day 1 (Study entry visit) ]
    The previous disease-modifying anti-rheumatic drugs therapy included auranofin, aurothioglucose, aurotioprol, azathioprine, chloroquine, ciclosporin, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, methotrexate sodium, minocycline, penicillamine, sodium aurothiomalate, sodium aurotiosulfate, sulfasalazine, and tiopronin. Number of participants with previous disease-modifying anti-rheumatic drugs therapy was reported.
  • Factors Related to Selection of Second Biologic Therapy Following an Insufficient Response or Intolerance to a Single Previous TNFi [ Time Frame: Baseline ]
    The factors included participant characteristics and the reasons that led to the selection of second biologic therapy following an insufficient response or intolerance to a single previous TNFi. The participant characteristics included participant's option for treatment and option for follow-up. The other reasons included RA disease (rheumatoid factor [RF] and cyclic citrullinated peptide [CCP] status), primary failure, and new treatment characteristics (rapidity of action, route of administration, frequency of administration, low infectious risk, and no lymphoma risk). Participants were included in more than one of these factors.
Original Secondary Outcome Measures
 (submitted: March 16, 2012)
  • Mean change in DAS28-ESR 12 months after change in biologic therapy [ Time Frame: approximately 14 years ]
  • Mean change in tender/swollen joint count (TJC/SJC) at 6 and 12 months [ Time Frame: approximately 14 years ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 14 years ]
  • Mean change in C-reactive protein at 6 and 12 months [ Time Frame: approximately 14 years ]
  • Quality of life: Health assessment questionnaires (HAQ) [ Time Frame: approximately 14 years ]
  • Proportion of patients remaining on their second biologic therapy at 6 and 12 months after starting [ Time Frame: approximately 14 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title An Observational Study of MabThera/Rituxan (Rituximab) and Alternative TNF-Inhibitors in Patients With Rheumatoid Arthritis and an Inadequate Response to a Single Previous TNF-Inhibitor
Official Title A Global Multi-centre Observational Study in RA Patients Who Are Non Responders or Intolerant to a Single TNF Inhibitor.
Brief Summary This multicenter, prospective, observational study will assess the efficacy of MabThera/Rituxan (rituximab) and alternative TNF-inhibitors in patients with rheumatoid arthritis who are non-responders or intolerant to a single previous TNF-inhibitor. Data will be collected from each patient from the time of change in biologic therapy for 12 months.
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population Rheumatoid arthritis patients who are non-responders or intolerant to a single TNF-inhibitor
Condition Rheumatoid Arthritis
Intervention Not Provided
Study Groups/Cohorts
  • Rituximab
    Eligible participants will receive rituximab as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
  • Alternative TNFi
    Eligible participants will receive alternative TNFi treatment as second biologic therapy in routine clinical practice and were observed for 12 months from the start of the second biologic therapy.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: November 28, 2016)
1239
Original Estimated Enrollment
 (submitted: March 16, 2012)
1262
Actual Study Completion Date March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Patients with rheumatoid arthritis (RA) who have not responded or have been intolerant to a single TNF-inhibitor therapy
  • Initiated on treatment with MabThera/Rituxan or an alternative TNF-inhibitor therapy, in accordance with the relevant Summary of Product Characteristics

Exclusion Criteria:

  • Patients whose second biologic therapy is given as part of a clinical trial studying RA treatment
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada,   Mexico,   Colombia,   France,   Germany,   Greece,   Italy,   Monaco,   Norway,   Portugal,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT01557348
Other Study ID Numbers MA22401
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor Hoffmann-La Roche
Collaborators Not Provided
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2016