A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00810199
First received: December 16, 2008
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: methotrexate
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab (TCZ) With or Without Methotrexate (MTX) and Possible Addition of Other Disease-modifying Anti-rheumatic Drugs (DMARDs) in Patients...

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.


Secondary Outcome Measures:
  • Percentage of Participants With American College of Rheumatology (ACR20) Response [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Percentage of Participants With ACR50 Response [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Percentage of Participants With ACR70 Response [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Percentage of Participants With ACR90 Response [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    ACR90 response is defined as a ≥ 90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Time to First ACR20 Response [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    Time in days from first administration of study drug until ACR20 response. ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Time to First ACR50 Response [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    Time in days from first administration of study drug until ACR50 response. ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate).

  • Time to First ACR70 Response [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    Time in days from first administration of study drug until ACR70 response. ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Time to First ACR90 Response [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    Time in days from first administration of study drug until ACR90 response. ACR90 response is defined as a ≥ 90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Area Under Curve (AUC) DAS28 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. AUC DAS28 was averaged over study days. Analysis of Covariance was adjusted for Baseline DAS28 as a covariate and treatment group and region as fixed factors. Higher calculated AUC values are worse (indicate higher disease activity).

  • Percentage of Participants With Disease Activity Score 28 (DAS28) Remission [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.

  • Percentage of Participants With DAS28 Low Disease Activity (LDAS) [ Time Frame: Weeks 24, 52 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2.

  • Change From Baseline in DAS28 Score [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A higher value indicated higher disease activity. A negative change from Baseline indicated improvement.

  • Percentage of Participants With Good or Moderate European League (EULAR) DAS28 Responses [ Time Frame: Baseline, 24, 52 ] [ Designated as safety issue: No ]

    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

    European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline < -1.2.

    EULAR Moderate response: DAS28 > 3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.


  • Change From Baseline in Swollen Joint Count [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.

  • Change From Baseline in Tender Joint Count [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.

  • Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (VAS) [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    The patients global assessment of disease activity was assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and was described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale (VAS) [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in Patient Global Assessment of Pain (VAS) [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.

  • Change From Baseline in C-Reactive Protein (CRP) [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

  • Change From Baseline in the Health Assessment Questionnaire Disability Index [ Time Frame: Baseline, Weeks 24, 52 ] [ Designated as safety issue: No ]
    The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Total Genant Modified Sharp Scores (GSS) [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    Radiographs were taken of each hand and foot at Baseline, Weeks 24, 52 and104 and were evaluated using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 98 and in the feet 42. The maximum scores for joint space narrowing (JSN) in the hands was104 and in the feet 48. The total score was the sum of scores for erosions and JSN. The maximum total modified GSS was 292. A lower number change from Baseline was better. Analysis of covariance model, with Baseline DAS28 as a covariate and treatment and site as fixed factors.

  • Change From Baseline in Joint Space Narrowing Score [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum scores for joint space narrowing (JSN) in the hands was 104 and in the feet 48 for a total possible score of 0 to 152. A lower change from Baseline indicated a better score. Analysis of covariance model included baseline x-ray and DAS28 as covariates and treatment group and region as fixed effects.

  • Change From Baseline in Erosion Score [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. The maximum erosion score in the hands was 98 and in the feet 42 for a total possible score of 0 to 140. A lower number change from Baseline indicated a better score.

  • Percentage of Participants Discontinuing Tocilizumab Due to Remission [ Time Frame: Weeks 52, 104 ] [ Designated as safety issue: No ]
    The percentage of participants who stopped treatment with tocilizumab due to remission.

  • Percentage of Participants Who Withdrew Due to Lack of Sufficient Therapeutic Response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Lack of Sufficient Therapeutic Response was defined as the patient not responding to the drug as expected.

  • Percentage of Participants Who Withdrew Due to Safety Reasons [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Safety reasons were defined as adverse events, intercurrent illness or death. An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.

  • Change From Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) [ Time Frame: Baseline, Weeks 24, 52, 104 ] [ Designated as safety issue: No ]
    The RAQoL is a disease specific patient-reported outcome measure that determines the effect rheumatoid arthritis has on a patient's quality of life consisting of 30 questions that are answered either yes=1 or no=0 for a total possible score ranging from 0 (best) to 30 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Academic Medical Center (AMC) Linear Disability Scale (ALDS) [ Time Frame: Baseline, Weeks 104 ] [ Designated as safety issue: No ]
    The Academic Medical Center (AMC) Linear Disability Score (ALDS) evaluates the participant's ability to perform activities of daily life consisting of 77 questions answered yes or no . The question difficulty and the patient's ability are arranged on a single hierarchical linear scale. ALDS scores range from 10 to 90 with a higher score representing higher functional status. A positive change from Baseline indicated improvement.

  • Area Under the Curve (AUC) From Baseline to Week 24 for ACR Response [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    ACR response was defined as an improvement (reduction) compared with baseline for both total joint count-68 joints and swollen joint count-66 joints, and for three of five variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) where 0=no pain to 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where: 0=no disease activity to 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. Area under the curve for ACR response to Week 24 was averaged over study days. Analysis of covariance model includes treatment group, region and baseline DAS28 (≤ 5.5 and > 5.5) as fixed factors.

  • Area Under the Curve (AUC) From Baseline to Week 52 for ACR Response [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
    ACR response was defined as an improvement (reduction) compared with baseline for both total joint count-68 joints and swollen joint count-66 joints, and for three of five variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) where 0=no pain to 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where: 0=no disease activity to 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].Area under the curve for ACR response to Week 52 averaged over study days. Analysis of covariance model includes treatment group, region and baseline DAS28 (<=5.5 and >5.5) as fixed factors.

  • Time to Tocilizumab Remission [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The time in days from initial study drug treatment to tocilizumab remission that occurred when the patient discontinued treatment with tocilizumab.

  • Time to Drug-Free Remission [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The time in days from initial study drug treatment to drug free remission that occurred when the participant was able to discontinue tocilizumab, methotrexate/placebo and open label disease-modifying antirheumatic drugs (DMARDS).

  • Time to Flare After Tocilizumab Remission [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The time in days to a flare (recurrence of disease symptoms) after the patient discontinued treatment with tocilizumab.

  • Time to Restart of Treatment After Discontinuation/Remission [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The time in days from treatment discontinuation or remission to the restart of treatment.


Enrollment: 556
Study Start Date: March 2009
Study Completion Date: January 2013
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.
Drug: tocilizumab [RoActemra/Actemra]
tocilizumab 8 mg IV every 4 weeks.
Other Name: RoActemra/Actemra
Drug: methotrexate
Approximately 15-17 mg methotrexate capsule orally once a week.
Placebo Comparator: Tocilizumab + Placebo
Tocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.
Drug: tocilizumab [RoActemra/Actemra]
tocilizumab 8 mg IV every 4 weeks.
Other Name: RoActemra/Actemra
Drug: placebo
Placebo matching methotrexate capsule taken orally once a week.

  Eligibility

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

Inclusion Criteria:

  • adult patients, ≥ 18 years of age;
  • moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) > 4.4);
  • inadequate response to methotrexate;
  • on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.

Exclusion Criteria:

  • prior treatment with a biologic;
  • Rheumatoid arthritis (RA) functional class IV;
  • known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
  • evidence of active malignant disease.
  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: NCT00810199

  Show 137 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications:
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00810199     History of Changes
Other Study ID Numbers: MA21488, 2008-001847-20
Study First Received: December 16, 2008
Results First Received: May 1, 2014
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014