Rituximab-Treatment in Addition to Leflunomide in Patients with active rheumatoid arthritis

• Conditions: Active rheumatoid arthritis (RA) Patients who have had an inadequate response to disease modifying anti-rheumatic drugs (not more than 3 DMARDs including leflunomide, not more than one anti-TNF failure) and currently have active disease despite at least 3-month treatment with leflunomide. Active disease is defined as DAS 28 > 3.2 and at least swollen joint count (SJC) = 3 and tender joint count (TJC) = 3 included in the 28 joint count.; MedDRA version: 14.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2009-015950-39-DE
• Lead Sponsor: Johann Wolfgang Goethe-Universität Frankfurt/M.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-28
• Last Update Posted: 25 January 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

-Male and female patients, 18 to 75 years of age, with active rheumatoid arthritis (RA) who have had an inadequate response to disease modifying anti-rheumatic drugs (not more than 3 DMARDs including leflunomide, not more than one anti-TNF failure) and currently have active disease despite at least 3-month treatment with leflunomide. Active disease is defined as DAS 28 > 3.2 and at least swollen joint count (SJC) = 3 and tender joint count (TJC) = 3 included in the 28 joint count.
-Male and female patients with rheumatoid arthritis for at least 3 months diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis.
- Willingness and capability to give written informed consent, and willingness to participate and to comply with the study protocol.
- Not more than 2 non-biological DMARDs other than leflunomide in history, which are washed out at least 4 weeks prior to first rituximab infusion
- Inadequat response to no more than one anti-TNF treatment
- Previous use of anti-TNF therapy is allowed. Patient will only be allowed to be pre-treated with a maximum of two anti-TNF therapies and only one stopped due to inadequate response. The second anti-TNF could be stopped for instance due to
intolerance, e.g. injection site reactions.

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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

-RA functional class IV: limited in ability to perform usual self-care, work, and other activities
- Male and female patients with other chronic inflammatory articular disease or systemic autoimmune disease
- Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms (Hepatitis B, C and HIV)
- Primary or secondary immunodeficiency
- Chronic, latent and acute infections of the lung
- Positive result of a Tb specific Interferon gamma release assay
- 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 filling out the patient's questionnaires
- History of a severe psychological illness or condition
- Known hypersensitivity to any component of the product or to murine proteins
- Severe heart failure (New York Heart Association Class III and IV) or severe, uncontrolled cardiac disease.
- Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test or planned pregnancy.
- Women of childbearing potential without adequate contraception (medically acceptable methods (pearl index < 1) are contraceptive implant, contraceptive injection, intrauterine device (IUD), or oral contraceptives taken for at least 3 months, which the patient agrees to continue using during the study, or a double-barrier method which must consist of a combination of any of the following: diaphragma, cervical cap, condom, or spermicide)
- History of alcohol, drug or chemical abuse (defined as impaired / questionable reliability) as well as neurotic personality.
- Participation in another investigational study within 4 weeks prior to the screening visit.
- Previous treatment with any B-cell depleting agents including rituximab
- Intolerance to ingredients of rituximab or murine proteins
- Pre-treatment with abatacept, tocilizumab or other non anti-TNF biologicals.
-Inadequate response to more than one anti-TNF-therapy
-Pre-treatment of more than two anti-TNF, only one is allowed to be stopped due to inadequate response. The second anti-TNF could be stopped due to intolerance, e.g.
injection site reactions.
- Corticosteroids at doses exceeding 10 mg per day of prednisolone or equivalents within the last 2 weeks or corticosteroids at instable doses within the last 2 weeks
-Intolerance or contraindication to drugs required for the treatment of the side effects of rituximab
-Previous treatment with any investigational medicinal product within last 3 months prior to baseline
•Receipt of a live vaccine within 4 weeks prior to treatment
•Intra- articular or parenteral corticosteroids within 4 weeks prior to screening visit
•Haemoglobin < 8.5 g / dl
-Neutrophil counts < 1.500 / µl
-Platelet count < 75.000 / µl
- Lower than 500 / µl (equivalent to 0,5 / nl) lymphocytes
-Serum creatinine > 1.4 mg / dl for women or 1.6 mg / dl for men
-AST or ALT > 2.5 times upper limit of normal
-IgG level < 5g/l

Study & Design

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