Efficacy and safety of rituximab in patients with rheumatoid arthritis - FIRST

• Conditions: Rheumatoid arthritis; MedDRA version: 8.1Level: PTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2006-001000-37-DE
• Lead Sponsor: Roche Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-06-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

•Age 18 to 80
•Active rheumatoid arthritis (DAS 28 =3.2)
•SJC =4 at screening and baseline
•TJC =4 at screening and baseline
•Patients with rheumatoid arthritis for at least 6 month diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis
•Not more than one TNFa- inhibitor in history
•Inadequate response to either etanercept (Enbrel) or infliximab (Remicade) or adalimumab (Humira). Inadequate response is defined as either a lack of response to the respective drug or loss of response to the respective drug or intolerance to the respective drug. Etanercept treatment must have been stopped at least 4 weeks prior to first rituximab infusion, treatment with infliximab or adalimumab at least 8 weeks prior to first rituximab in-fusion.
•Willingness and capability to give written informed consent, written consent for data protection (legal requirement in Germany: datenschutzrechtliche Einwilligung) and willingness to participate and to comply with the study.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion criteria related to RA
•Functional class IV as defined by the ACR classification of Functional Status in Rheuma-toid Arthritis.
Exclusion criteria related to general health conditions
•Patients with other chronic inflammatory articular disease or systemic autoimmune dis-ease, e.g. Systemic lupus erythematosus, Sjögren’s syndrome, active rheumatoid vascu-litis, a history of systemic diseases associated with arthritis, chronic fatigue syndrome
•Any active infection, a history of recurrent clinically significant infection, a history of re-current bacterial infections with encapsulated organisms
•Primary or secondary immunodeficiency
•History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised
•Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome
•Neuropathy that can interfere with quality of life and/or pain assessment.
•Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
•Known hypersensitivity to any component of the product or to murine proteins.
•Women, pregnant, nursing or of childbearing potential with a positive pregnancy test (urine test)
•Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier) for up to 12.5 months after first infusion of ri-tuximab
•History of alcohol, drug or chemical abuse within 6 month prior to screening
•Lack of peripheral venous access
Exclusion criteria related to medications
•Previous treatment with rituximab or intolerance to rituximab
•Previous treatment with abatacept
•Corticosteroids at doses exceeding 10 mg per day of prednisolone or the equivalent within the last 2 weeks prior to the first rituximab infusion or corticosteroids at instable doses within the last 2 weeks prior to the first rituximab infusion
•Intolerance or contraindication to drugs required for the treatment of the side effects of ri-tuximab (e.g. paracetamol, acetaminophen, diphenhydramine, p.o. and i.v. corticosteroids, anti-emetics or H1 blockers)
•Concurrent treatment with any DMARD (apart from MTX), any TNFalpha inhibitor, or any anti-IL or CTLA4 Ig or other biologic or any investigational agent
•Receipt of a live vaccine within 4 weeks prior to treatment
•Intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit
Exclusion criteria related to lab findings
•Haemoglobin < 8.5 g/dl
•Neutrophil counts < 1.500 / µl
•Platelet count < 75.000 / µl
•Lower than 1 x 700/µl lymphopenia for more than three months prior to inclusion.
•Serum creatinine > 1.4 mg/dl for women or 1.6 mg/dl for men.
•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times upper limit of normal.
•Positive HIV or hepatitis C serology as well as positive tests for hepatitis B surface antigen (HBsAg) and/or positive tests for hapatitis B core antibody (HbcAb)).
Exclusion criteria related to formal aspects.
•Patients who have paritcipated in this study before.
•Patients who participate currently in another clinical trial or patients who participated in another clinical trial during the last 30 days.
•Patients who are underage or patients who are incapable to understand the aim, impor-tance and consequences of the s

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of rituximab in rheumatoid arthritis after inadequate response to a single TNF-alpha inhibitors;Secondary Objective: To demonstrate that treatment with rituximab in rheumatoid arthritis is safe;Primary end point(s): change of DAS28 at week 24