A randomized, phase 3, controlled, double-blind, parallel-group, multicenter study to evaluate the safety and efficacy of rituximab in combination with methotrexate (MTX) compared to MTX alone, in methotrexate-naïve patients with active rheumatoid arthritis.

• Register: EUCTR
• Last refreshed on: 19 August 2013
• Main ID: EUCTR2005-002395-15-CZ
• Date of registration: 27/02/2006
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A randomized, phase 3, controlled, double-blind, parallel-group, multicenter study to evaluate the safety and efficacy of rituximab in combination with methotrexate (MTX) compared to MTX alone, in methotrexate-naïve patients with active rheumatoid arthritis.
• Scientific title: A randomized, phase 3, controlled, double-blind, parallel-group, multicenter study to evaluate the safety and efficacy of rituximab in combination with methotrexate (MTX) compared to MTX alone, in methotrexate-naïve patients with active rheumatoid arthritis.
• Date of first enrolment: 27/02/2006
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002395-15
• 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: yes Placebo: yes Other:

Countries of recruitment

Czech Republic, Denmark, Finland, Germany, Italy, Spain, Sweden, 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 diagnosed for at least 8 weeks, prior to baseline, but no more than 4 years, according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis.
3. Patients naïve to, and considered to be candidates for, treatment with methotrexate.
4. Swollen joint count (SJC) = 8 (66 joint count), and tender joint count (TJC) = 8 (68 joint count) both at screening and baseline.
5. At screening CRP = 1.0 mg/dL (10 mg/L).
6. Miniumum age 18
7. Glucocorticoids = 10 mg/day prednisolone or equivalent is 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 be willing to receive oral folate.
11. For RF negative patients only, radiographic evidence of at least one joint with definite erosion attributable to RA.
12. Patients who are to receive, or who are currently receiving, treatment for RA on an outpatient basis.
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:
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 Sjögren’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 (including, but not limited to, gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (including, but not limited to, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or any 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 during the study.
6. Lack of peripheral venous access.
7. Pregnancy or breast feeding.
8. Significant and/or uncontrolled cardiac or pulmonary disease (including obstructive pulmonary disease).
9. Evidence of significant concomitant disease, including but not limited to, 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 completion of oral antiinfectives within 2 weeks prior to baseline.
12. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline.
13. History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to 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 swelling (e.g. Parkinsons 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. Previous treatment with any approved or investigational biologic agent for RA.
19. Previous treatment with an anti-alpha 4 integrin antibody or co-stimulation modulator.
20. Concurrent treatment with any biologic agent or DMARD other than MTX. Treatment must be discontinued 14 days prior to baseline, except for the following: azathioprine for = 28 days; leflunomide for = 8 weeks (or = 14 days after 11 days of standard cholestyramine or activated charcoal washout).
21. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3,

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Trade Name: MabThera
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)

Main Objective: 1. To determine the efficacy of rituximab in the prevention of progression in structural joint damage and to evaluate the safety of rituximab in patients with active rheumatoid arthritis initiating treatment with MTX.
2. To evaluate the efficacy of rituximab in improving patient’s physical function and signs and symptoms of RA.
3. To investigate by a population analysis approach the pharmacokinetics (PK) of rituximab in the target RA patient population and the influence of covariates on the PK parameters.
4. To explore the long-term efficacy and safety of further courses
of rituximab.

Primary end point(s): The primary endpoint is the change from screening in total modified Sharp score at week 52 using the modified ITT population.

Secondary Objective:

Secondary ID(s)

WA17047

2005-002395-15-FI