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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00996203
First received: October 15, 2009
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This open-label single arm study will evaluate the efficacy and safety of tocili zumab added to traditional disease-modifying antirheumatic drugs (DMARDs) in pat ients with moderate to severe active rheumatoid arthritis and an inadequate resp onse to DMARDs. Patients will receive tocilizumab 8 mg/kg by intravenous infusio n every 4 weeks for 24 weeks, in addition to their current non-biologic DMARDs a t stable doses. Anticipated time on study treatment is 24 weeks, and the target sample size is 200.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: DMARDs (disease-modifying antirheumatic drugs)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Health Assessment Questionnaire (HAQ) Score [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Pain Score as Assessed by Visual Analogue Scale (VAS) [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.

  • Change in EQ-5D Score at Week 24 From Baseline [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    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. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.

  • Erythrocyte Sedimentation Rate [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    ESR (mm/hr) is used to determine the acute phase response.


Enrollment: 201
Study Start Date: October 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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

  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 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
  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: NCT00996203

Locations
Russian Federation
Chelyabinsk, Russian Federation, 454076
Cherkess, Russian Federation, 369000
Ekaterinburg, Russian Federation, 620102
Irkutsk, Russian Federation, 664047
Izhevsk, Russian Federation, 426009
Kaliningrad, Russian Federation, 236016
Kemerovo, Russian Federation, 650099
Kirov, Russian Federation, 610028
Krasnodar, Russian Federation, 350086
Kursk, Russian Federation, 305007
Moscow, Russian Federation, 115682
Moscow, Russian Federation, 129110
Moscow, Russian Federation, 123060
Moscow, Russian Federation, 115522
Moscow, Russian Federation, 121359
Nizhny Novgorod, Russian Federation, 603126
Petrozavodsk, Russian Federation, 185019
Rostov-na-Donu, Russian Federation, 344022
Smolensk, Russian Federation, 214001
Surgut, Russian Federation, 628408
Tjumen, Russian Federation, 625023
UFA, Russian Federation, 450005
Ulyanovsk, Russian Federation, 432063
Veliky Novgorod, Russian Federation, 173008
Voronezh, Russian Federation, 394066
Yaroslavl, Russian Federation, 150062
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00996203     History of Changes
Other Study ID Numbers: ML22665
Study First Received: October 15, 2009
Results First Received: April 7, 2014
Last Updated: June 30, 2014
Health Authority: Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014