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A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.

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: NCT00996203
Recruitment Status : Completed
First Posted : October 16, 2009
Results First Posted : July 2, 2014
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 15, 2009
First Posted Date  ICMJE October 16, 2009
Results First Submitted Date  ICMJE April 7, 2014
Results First Posted Date  ICMJE July 2, 2014
Last Update Posted Date March 29, 2018
Actual Study Start Date  ICMJE October 31, 2009
Actual Primary Completion Date February 14, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2014)
  • Health Assessment Questionnaire (HAQ) Score [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit ]
    HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. Withdrawal Visit is the final visit prior to the withdrawal of the subject from the study.
  • Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ]
    HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
  • Change in HAQ Score at Week 24 [ Time Frame: Baseline and Week 24 ]
    HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.
Original Primary Outcome Measures  ICMJE
 (submitted: October 15, 2009)
Quality of life: HAQ and EQ-5D scores [ Time Frame: every 4 weeks up to week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
  • Pain Score as Assessed by Visual Analogue Scale (VAS) [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    Participant's global assessment of pain was assessed using a 100-millimeter (mm) horizontal VAS (0 to 100 mm) with 0=pain absent and 100=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain.
  • European Quality of Life - 5 Dimensions (EQ-5D) Score [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
  • Change in EQ-5D Score at Week 24 From Baseline [ Time Frame: Baseline and Week 24 ]
    EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression. Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Minimum clinically significant change in EQ-5D corresponds to the parameter differences before and after treatment = 0.10. Graduations of assessment of the therapy efficacy by EQ-5D are: Difference (Δ) EQ-5D less than (<)0.10 points: none; 0.10 less than or equal to (≤)Δ EQ-5D ≤0.24: minimal effect; 0.24≤ Δ EQ-5D <0.31: satisfactory effect; Δ EQ-5D greater than or equal to (≥)0.31 points: pronounced effect.
  • General Health Score as Assessed by EQ-5D VAS [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.
  • Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality. Positive response was defined as an increase of EQ-5D score by 0.1 or more i.e. it is a clinically significant increase.
  • Change in General Health Assessed by VAS [ Time Frame: Baseline and Week 24 ]
    Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state. The participants were asked to mark the line that corresponded to assessment of general health quality.
  • Disease Activity Score Based on 28-Joint Count (DAS28) [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
  • Change in DAS28 Score From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ]
  • Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR mm/hour, and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Disease activity: 0=remission (DAS28 less than [<] 2.6), I=low (DAS28 less than or equal to [≤]2.6 to <3.2), II=moderate (DAS28=3.2 to 5.1), III=high (DAS28 greater than [>]5.1).
  • Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ]
    ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) and in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase response: C-reactive protein (CRP) or ESR.
  • Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ]
    The DAS28-based EULAR response criteria were used to measure individual response as no effect, good effect, and moderate effect, depending on the extent of change from baseline and the level of disease activity reached. Good effect: change from baseline >1.2 with DAS28 score ≤3.2; moderate effect: change from baseline >1.2 with DAS28 score 3.2 to 5.1 or change from baseline >0.6 to <1.2 with DAS28 score <3.2; no effect: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 score >5.1.
  • C-Reactive Protein [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ]
    CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.
  • Erythrocyte Sedimentation Rate [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ]
    ESR (mm/hr) is used to determine the acute phase response.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2009)
  • Disease activity (DAS28), ACR and EULAR responses, CRP, ESR [ Time Frame: every 4 weeks up to week 24 ]
  • Safety and tolerability: AEs. laboratory parameters [ Time Frame: throughout study, laboratory assessments every 4 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.
Official Title  ICMJE Local Open-label Multicenter Study to Evaluate the Quality of Life in Patients With Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to DMARDs When Adding Tocilizumab (TCZ)
Brief Summary This open-label single arm study will evaluate the efficacy and safety of tocilizumab added to traditional disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis and an inadequate response to DMARDs. Patients will receive tocilizumab 8 mg/kg by intravenous infusion every 4 weeks for 24 weeks, in addition to their current non-biologic DMARDs at stable doses. Anticipated time on study treatment is 24 weeks, and the target sample size is 200.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: tocilizumab [RoActemra/Actemra]
    8 mg/kg iv every 4 weeks for 24 weeks
  • Drug: DMARDs (disease-modifying antirheumatic drugs)
    stable doses at investigator's prescription
Study Arms  ICMJE Experimental: 1
Interventions:
  • Drug: tocilizumab [RoActemra/Actemra]
  • Drug: DMARDs (disease-modifying antirheumatic drugs)
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  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 16, 2012)
201
Original Estimated Enrollment  ICMJE
 (submitted: October 15, 2009)
200
Actual Study Completion Date  ICMJE February 14, 2011
Actual Primary Completion Date February 14, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • adult patients, >/= 18 years of age
  • moderate to severe active rheumatoid arthritis of >/=6 months duration
  • inadequate clinical response to current non-biologic DMARDs
  • current DMARDs must be at stable dose for 8 weeks prior to study entry
  • oral corticosteroids (</=10mg/day prednisone or equivalent) and NSAIDs must be at stable dose for >/=4 weeks prior to screening

Exclusion Criteria:

  • rheumatic autoimmune disease other than RA
  • history of or current inflammatory joint disease other than RA
  • previous treatment with any biologic DMARD
  • functional class IV as defined by the ACR classification
  • intra-articular or parenteral corticosteroids within 6 weeks prior to screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00996203
Other Study ID Numbers  ICMJE ML22665
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP