A Study Assessing the Safety and Efficacy of Subcutaneous RoActemra/Actemra Alone or in Combination With Non-biologic Antirheumatics in Rhuematoid Arthritis Patients in Latin America With Inadequate Response to Non-biologic Antirheumatic Drugs.

Study Overview
=================
Brief Summary
-----------------
This multi-center, open-label, single-arm, Phase IIIb study will evaluate the safety and efficacy of subcutaneous RoActemra/Actemra alone or in combination with non-biologic disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis patients in Latin America with an inadequate response to non-biologic DMARDs.

Official Title
-----------------
A MULTICENTER, OPEN LABEL STUDY TO EVALUATE EFFICACY AND SAFETY OF TOCILIZUMAB GIVEN SUBCUTANEOUSLY IN MONOTHERAPY AND IN COMBINATION WITH NON-BIOLOGIC DMARDS IN PATIENTS WITH MODERATE TO SEVERE ACTIVE RHEUMATOID ARTHRITIS IN LATIN AMERICA

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: tocilizumab [RoActemra/Actemra]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients >/= 18 years of age. Patients with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria. Patients with moderate to severe RA (DAS-ESR 28 >/= 3.2). Receiving non-study treatment on an outpatient basis. Oral corticosteroids (</= 10 mg/day prednisone or equivalent), NSAIDs and non-biologic DMARDs are permitted if on a stable dose regimen for >/= 4 weeks prior to Baseline. Inadequate response to previous non-biologic DMARD therapy. Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential cannot be pregnant. Exclusion Criteria: Presence of clinically significant medical conditions. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease that might predispose to perforation. Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections. Any infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening. Clinically significant findings on lab tests and/or hepatits B or C, or HIV screenings. Active TB requiring treatment within the previous 3 years. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years. History of alcohol, drug, or chemical abuse within 1 year prior to Screening. Neuropathies or other conditions that might interfere with pain evaluation. Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted. Functional Class IV as defined by the ACR Classification of Functional Status in-Rheumatoid Arthritis (Appendix 2). Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16. Prior history of or current inflammatory joint disease other than RA. Previous exposure to RoActemra/Actemra (either IV or SC). Prior treatment with a biologic agent. Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening. Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation. Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline. Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: RoActemra/Actemra<br> | Drug: tocilizumab [RoActemra/Actemra]<br>* 162 mg will be administered once weekly by subcutaneous injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) Remission Rate |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events (AE) |  | 60 weeks | 
| Efficacy: Change in DAS28-ESR |  | From baseline to Week 52 | 
| Efficacy: ACR/EULAR responses |  | 52 weeks | 
| Efficacy: Change in disease activity (CDAI/SDAI) |  | From baseline to Week 52 | 
| Efficacy: Change in joint swelling/tenderness (SJC/TJC) |  | From baseline to Week 52 | 
| Safety: Assessment of immunogenicity |  | 60 weeks | 
| Patient-reported outcomes |  | 60 weeks | 
| Efficacy: DAS28-ESR Remission Rate |  | 52 weeks | 
| Efficacy: Proportion of patients who maintain DAS28 Remission/LDA |  | From Week 24 to Week 52 | 
| Safety: Rates of AE leading to dose modification or study withdrawal |  | 52 weeks | 
| Safety: Assessment of physical examination and vital signs |  | 52 weeks | 
| Safety: Incidence of clinically significant laboratory abnormalities following treatment |  | 52 weeks |