An Open-label Study With Tocilizumab in Patients With Rheumatoid Arthritis in a Local Environment

Study Overview
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Brief Summary
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This open-label, multi-center study in a local environment will evaluate the safety and the effect on disease activity with regard to reduction in signs and symptoms over 6 months of treatment in patients with moderate to severe active rheumatoid arthritis who experienced an inadequate response to a non-biologic DMARD. Tocilizumab 8 mg/kg will be administered as an intravenous infusion every 4 weeks for a total of 6 infusions as monotherapy or in combination with methotrexate (MTX). The anticipated time of study treatment is 24 weeks.

Official Title
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Open Label, Multicenter, Trial to Evaluate Safety, Tolerability and Efficacy of Tocilizumab in Monotherapy or in Combination With MTX in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non Biologic DMARDs

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: tocilizumab [RoActemra]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients >/=18 years of age Moderate to severe rheumatoid arthritis defined as DAS 28>3.2 Body weight </=150 kg Patient on at least 1 non-biologic DMARD on a stable dose for at least 8 weeks at any time prior to study start Inadequate clinical response to a stable dose of a non-biologic DMARD Exclusion Criteria: Major surgery within 8 weeks prior to screening or planned major surgery within 6 months following enrollment Rheumatic autoimmune disease other than rheumatoid arthritis (RA) Functional class IV as defined by the ACR classification History or current inflammatory joint disease other than RA Previous treatment with any cell depleting therapy Previous treatment with methotrexate Previous treatment with tocilizumab Previous treatment with any biologic drug that is used in the treatment of RA

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br> | Drug: tocilizumab [RoActemra]<br>* tocilizumab 8 mg/kg intravenous infusion every 4 weeks for a total of 6 infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Related AEs, Discontinuation Due to AEs, or Death |  | Baseline, every 4 weeks through Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Clinically Significant Improvement Assessed Using Disease Activity Score Based on 28 Joints (DAS28) | DAS28 calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and participant's global assessment (PtGA) of disease activity by Visual analog Scale (VAS; participant rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 less than or equal to (≤) 3.2 equals (=) low disease activity (LDA), DAS28 greater than (>) 3.2 to 5.1 = moderate to high disease activity. A reduction of at least 1.2 units in DAS28 was considered clinically significant improvement. | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Percentage of Participants Achieving LDA Assessed Using DAS28 | DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. DAS28 less than (<) 3.2 = LDA. | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Percentage of Participants Achieving Remission Assessed Using DAS28 | DAS28 calculated from the SJC and TJC using the 28 joints count, the ESR (mm/hour) and PtGA of disease activity (VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity. Participants were considered in remission when reaching a DAS28 score <2.6. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Percentage of Participants With American College of Rheumatology (ACR) 20 Percent (%), 50% or 70% Improvement (ACR20/ACR50/ACR70) | The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) C-reactive protein (CRP) at each visit. | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Time To Achieve ACR20/ACR50/ACR70 | The ACR response rates ACR20/ACR50/ACR70 are defined as ≥20%, ≥50%, or ≥70% improvement, respectively, in SJC and TJC, as well as a ≥20%, ≥50%, or ≥70% improvement, respectively, in 3 of the 5 remaining core ACR assessments: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via (HAQ, and 5) CRP at each visit. The median time to achieve ACR20/ACR50/ACR70 was calculated using Kaplan-Meier estimates. | Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| SJC and TJC | 28 joints were assessed for swelling and tenderness. Joints were classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) giving a total possible SJC and TJC score of 0 to 28 each. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Assessment of Pain by the Participant Using Visual Analog Scale (VAS) | The participants assessed their pain using a 0 to 100 millimeter (mm) horizontal 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. The participants marked the line corresponding to their level of pain and the distance from the left edge was measured. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Assessment of Global Disease by the Participant Using VAS | The participant's global assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS by the participant. 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). The participants marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Assessment of Global Disease by the Physician Using Visual Analog Scale (VAS) | The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal 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). The physician marked the line corresponding to their assessment of disease activity and the distance from the left edge was measured. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Assessment of Physical Function Using Health Assessment Questionnaire (HAQ) | Physical function was assessed using the HAQ. The HAQ scores range from 0 to 3 with, 0: no assistance needed, 1: participant uses a special device for day-to-day activities, 2: participant usually needs help from another person, and 3: participant uses BOTH a special device AND another person's help for day-to-day activities. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Mean C-Reactive Protein (CRP) Levels | CRP is an acute phase reactant and levels of CRP increase with inflammation. CRP is measured as milligrams per liter (mg/L). | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Mean Erythrocyte Sedimentation Rate (ESR) Levels | ESR is an acute phase reactant and levels of ESR increase with inflammation. ESR is measured as mm/hour. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 36, 48 and 52 | 
| Percentage of Participants Experiencing Fatigue |  | Baseline and Weeks 4, 8, 12, 16, 20, and 24 | 
| Number of Participants Who Discontinued Tocilizumab |  | Week 52 |