STUDY TO EVALUATE THE EFFICACY, SAFETY AND TOLERABILITY OF SUBCUTANEOUS (SC) TOCILIZUMAB (TCZ) IN SUBJECTS WITH RHEUMATOID ARTHRITIS

Phase 1

Conditions: Rheumatoid Arthritis
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2013-002429-52-ES

Lead Sponsor: Roche Farma S.A

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 420

Inclusion Criteria

Patients must meet the following criteria for study entry:
1.Able and willing to give written informed consent and comply with the requirements of the study protocol.
2.Patients at least 18 years of age.
3.Patients with a diagnosis of active RA (DAS28-ESR > 3.2), according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria of > 6 months duration.
4.Oral corticosteroids (?10 mg/day prednisone or equivalent) and nonsteroidal anti inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for ?4 weeks prior to Baseline.
5.Permitted non-biologic DMARDs are allowed if at a stable dose for at least 4 weeks prior to Baseline
6.Receiving treatment on an outpatient basis
7. Females of childbearing potential and males with female partners of childbearing potential may participate in this study only if using a reliable means of contraception (e.g., physical barrier [patient or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during the study and for at least 3 months following the last dose of TCZ.
8.If female of childbearing potential, the patient must have a negative pregnancy test at Screening and Baseline visits.
9.Patients with intolerance or inadequate response to MTX or other nb DMARDs or inadequate response to a first anti-TNF agent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 420
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A patient will be excluded if the answer to any of the following statements is ?yes?:

General:
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.
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 (e.g., gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, and arthropathy of inflammatory bowel disease).
Excluded Previous or Concomitant Therapy:
Exposure to TCZ (either intravenous [IV] or SC) at any time prior to Baseline.
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, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti CD19, and anti-CD20.
Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
Intraarticular or parenteral corticosteroids within 4 weeks prior to Baseline.
Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.
Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
Previous treatment with Abatacept
Exclusions for General Safety:
History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal (GI) disease.
History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn?s disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation.
Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of screening.
Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patients treated for TB with no recurrence in 3 years are permitted.
Current liver disease as determined by the Investigator.
Positive hepatitis B surface antigen or hepatitis C antibody.
Primary or secondary immunodeficiency (history of or currently active).
Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma