A randomized, placebo controlled, multicenter clinical study investigating efficacy of rituximab (MabThera/Rituxan) in the inhibition of joint structural damage assessed by magnetic resonance imaging in patients with rheumatoid arthritis and inadequate response to methotrexate - the R.A. SCORE study. - RA-SCORE

• Register: EUCTR
• Last refreshed on: 27 October 2014
• Main ID: EUCTR2007-001585-33-DE
• Date of registration: 14/04/2008
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A randomized, placebo controlled, multicenter clinical study investigating efficacy of rituximab (MabThera/Rituxan) in the inhibition of joint structural damage assessed by magnetic resonance imaging in patients with rheumatoid arthritis and inadequate response to methotrexate - the R.A. SCORE study. - RA-SCORE
• Scientific title: A randomized, placebo controlled, multicenter clinical study investigating efficacy of rituximab (MabThera/Rituxan) in the inhibition of joint structural damage assessed by magnetic resonance imaging in patients with rheumatoid arthritis and inadequate response to methotrexate - the R.A. SCORE study. - RA-SCORE
• Date of first enrolment: 19/08/2008
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-001585-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Denmark, Estonia, France, Germany, Greece, Latvia, Lithuania, Netherlands, Spain

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 active RA for at least 3 months diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of RA
3. Disease duration = 10 years
4. Either anti-cyclic citrullinated peptide (anti-CCP) (= 20 Units) or rheumatoid factor positive (=20 IU/mL) or both
5. Active disease as defined by DAS28-CRP = 3.2
6. Evidence of erosive disease and/or clinical synovitis in a signal (MRI) joint (metacarpophalangeal and/or wrist)
• RA duration > 1 year: at least one erosion evaluated by a radiograph at the X-ray screening visit and evidence of clinical synovitis
• RA duration = 1 year: evidence of clinical synovitis*
7. Age = 18 and = 80 years
8. Glucocorticoids =10 mg/day prednisolone or equivalent permitted if stable for at least 4 weeks prior to baseline
9. Use of non-steroidal anti inflammatory drugs is permitted if stable for at least 4 weeks prior to baseline
10. 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
11. Experiencing inadequate response to MTX at a dose of 12.5 25 mg/week (p.o. or parenteral) for at least 12 weeks, with the last 4 weeks prior to baseline maintained at a stable dose. Minimal MTX doses of 7.5 or 10 mg/week are permitted only in case of documented intolerance to higher doses.

*In the event that clinical synovitis is not confirmed by MRI assessment at baseline, the patient will be excluded from 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:
Related to RA:
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. Bed-bound or wheelchair bound patients
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., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or any overlap syndrome)
4. Diagnosis of juvenile idiopathic arthritis, also known as juvenile RA and/or RA before age 16.

Related to General Health:
1. Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of randomization
2. Lack of peripheral venous access
3. Pregnancy or breast feeding
4. Significant cardiac or pulmonary disease, including obstructive pulmonary disease
5. Evidence of significant, uncontrolled, concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation
6. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection
7. 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 prior to baseline or completion of oral anti-infectives within 2 weeks prior to baseline
8. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline
9. History of serious recurrent or chronic infection (patients will be screened for chest infections using a chest radiograph at screening if not previously performed within the 12 weeks prior to screening)
10. History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell or squamous cell carcinoma of the skin that has been excised and cured)
11. 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., Parkinson’s disease, cerebral palsy, diabetic neuropathy)
12. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.

Related to medications:
1. History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins
2. Previous treatment with any approved or investigational biologic agent for RA
3. Previous treatment with an anti-alpha 4 integrin antibody or co stimulation modulator
4. Previous treatment with any B cell modulating or cell depleting therapies, including investigational agents (e.g., CAMPATH, anti CD4, anti-CD5, anti CD3, anti CD19, anti-CD11a, anti-CD22, anti BLys/BAFF, and anti-CD20)
5. Treatment with any investigational agent within 28 days of baseline or five half lives of the investigational drug (whichever is the longer)
6. Receipt of any vaccine within 28 days prior to baseline. It is recommended that a patient’s vaccination record and the

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

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Trade Name: MabThera 500mg
Product Name: MabThera 500mg
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: 1. To investigate the efficacy of rituximab (1000 mg x 2) in the inhibition of joint structural damage progression assessed by using MRI in patients with an inadequate clinical response to MTX
2. To investigate the efficacy of rituximab (1000 mg x 2) in the improvement of synovitis and osteitis measured by MRI in patients with an inadequate clinical response to MTX
3. To explore the efficacy of rituximab (500 mg x 2) in the inhibition of joint structural damage progression and in the improvement of synovitis and osteitis assessed by using MRI in patients with an inadequate clinical response to MTX
4. To investigate the efficacy and safety of repeated courses of rituximab
5. To evaluate additional exploratory endpoints, including those relating to MRI of targeted joints and surrounding structures.

Secondary Objective: N/A

Primary end point(s): The change in the MRI bone erosion score (assessed using RAMRIS) between baseline and week 24 in patients receiving rituximab 1000 mg i.v. x 2 compared to those receiving placebo i.v. x 2.

Secondary ID(s)

2007-001585-33-LT

MA21056