Estudio internacional, randomizado, doble ciego, para evaluar la eficacia y seguridad de diversos regímenes de retratamiento con rituximab en combinación con metotrexato, en pacientes con AR que manifiestan una respuesta inadecuada a metotrexato. A randomised, double-blind, international study to evaluate the efficacy and safety of various re-treatment regimens of rituximab in combination with methotrexate in RA patients with an inadequate response to methotrexate.

• Register: EUCTR
• Last refreshed on: 28 August 2014
• Main ID: EUCTR2005-002396-33-ES
• Date of registration: 28/10/2005
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: Estudio internacional, randomizado, doble ciego, para evaluar la eficacia y seguridad de diversos regímenes de retratamiento con rituximab en combinación con metotrexato, en pacientes con AR que manifiestan una respuesta inadecuada a metotrexato. A randomised, double-blind, international study to evaluate the efficacy and safety of various re-treatment regimens of rituximab in combination with methotrexate in RA patients with an inadequate response to methotrexate.
• Scientific title: Estudio internacional, randomizado, doble ciego, para evaluar la eficacia y seguridad de diversos regímenes de retratamiento con rituximab en combinación con metotrexato, en pacientes con AR que manifiestan una respuesta inadecuada a metotrexato. A randomised, double-blind, international study to evaluate the efficacy and safety of various re-treatment regimens of rituximab in combination with methotrexate in RA patients with an inadequate response to methotrexate.
• Date of first enrolment: 27/12/2005
• Target sample size: 375
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002396-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: Single blind: Double blind: yes Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Different dose and regimen of rituximab

Countries of recruitment

Finland, Germany, Hungary, Italy, Slovakia, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Able and willing to give written informed consent and comply with the requirements of the study protocol.
2. Patients with rheumatoid arthritis for at least 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of rheumatoid arthritis.
3. Receiving treatment on an outpatient basis.
4. Swollen joint count (SJC) = 8 (66 joint count), and tender joint count (TJC) = 8 (68 joint count) at screening and baseline.
5. At screening, either CRP = 0.6 mg/dL (6 mg/L) OR ESR = 28 mm/h.
6. Minimum age 18 years.
7. Glucocorticoids = 10 mg/day prednisolone or equivalent permitted if stable for at least 4 weeks prior to baseline.
8. Use of NSAIDs is permitted if stable for at least 2 weeks prior to baseline.
9. For patients of reproductive potential (males and females), use of a reliable means of contraception (e.g. hormonal contraceptive, patch, intrauterine device, physical barrier) throughout study participation.
10. Must have an inadequate response to MTX and have been receiving and tolerating this at a dose of 10-25 mg/wk (p.o. or parenteral) for at least 12 weeks, with the last 4 weeks prior to baseline at a stable dose.

Are the trial subjects under 18?
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:
1. Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis or Felty’s syndrome). Secondary Sjogren’s syndrome or secondary limited cutaneous vasculitis with RA is permitted.
2. Functional class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis.
3. History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., SLE, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome).
4. Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before age 16.
5. Any surgical procedure, including bone/joint surgery/Synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 48 weeks of randomization.
6. Lack of peripheral venous access.
7. Pregnancy or lactation.
8. Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
9. Evidence of significant uncontrolled concomitant disease such as nervous system, renal, hepatic, endocrine or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation.
10. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
11. Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or oral anti-infectives within 2 weeks prior to baseline.
12. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks of baseline.
13. History of serious recurrent or chronic infection (to check for chest infection a chest x-ray will be performed at screening if not performed within 12 weeks of screening).
14. History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured).
15. Any neurological (congenital or acquired), vascular or systemic disorder which could affect any of the efficacy assessments, in particular, joint pain and swellin (e.g. Parkinson’s disease, cerebral palsy, diabetic neuropathy).
16. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.
17. History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins.
18. Concurrent treatment with any biologic agent or DMARD other than MTX. Treatment with all DMARDS (including etanercept) must be discontinued 14 days prior to baseline, except for the following: azathioprine = 28 days; leflunomide for = 8 weeks (or = 14 days after 11 days of standard cholestyramine or activated charcoal washout); infliximab = 8 weeks; adalimumab = 8 weeks. In the event that abatacept becomes an approved treatment for RA during the course of this study, this must also be discontinued for = 8 weeks prior to baseline.
19. Previous treatment with > 1 biological agent approved for use in RA.
20. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti- CD4, anti-CD

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Artritis Reumatoide (Rheumatoid arthritis)

Intervention(s)

Trade Name: MabThera 500 mg
Product Name: MabThera
Product Code: Ro 45-2294
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
CAS Number: 174722-31
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Proportion of patients with an ACR20 response at Week 48. In addition, responders and non-responders will also be analyzed.

Main Objective: 1. To determine if a second course with an increased dose of rituximab is associated with improved responses compared to re-treatment with the same dose.
2. To determine if there is a difference in response rates if a total annual dose of 2g rituximab is given as either a single course (2 × 1000 mg) or as divided courses (two courses each of 2 × 500 mg, given 24 weeks apart).
3. To investigate the pharmacokinetics of rituximab associated with 2 courses of treatment.

Secondary Objective:

Secondary ID(s)

WA17044