A randomized, double-blind, parallel group study of the safety and reduction of signs and symptoms during treatment with MRA versus placebo, in combination with methotrexate, in patients with moderate to severe active rheumatoid arthritis.
- Conditions
- Rheumatoid Arthritis
- Registration Number
- EUCTR2004-003741-40-AT
- Lead Sponsor
- F. Hoffmann La-Roche AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 630
1. Able and willing to give written informed consent and comply with the requirements of the study protocol.
2. Patients with rheumatoid arthritis of = 6 months duration, diagnosed according to the revised 1987 American College of Rheumatology (ACR; formerly American Rheumatism Association) criteria.
3. Receiving treatment on an outpatient basis.
4. Prior to randomization, will have discontinued etanercept for = 2 weeks, infliximab or adalimumab for = 8 weeks (see exclusion # 5), anakinra for = 1 week, leflunomide for = 12 weeks (or = 4 weeks after 11 days of standard cholestyramine washout).
5. Have received methotrexate for at least 12 weeks immediately prior to baseline, of
which the last 8 weeks prior to baseline must have been at a stable dose of between 10 and 25 mg/week (p.o. or parenteral).
6. All DMARDs, other than MTX, withdrawn prior to baseline.
7. Swollen joint count (SJC) = 6 (66 joint count) and tender joint count (TJC) = 8 (68
joint count) at screening and baseline.
8. At screening either CRP = 1 mg/dL (10 mg/L) or ESR = 28 mm/hr
9. Age = 18 years
10. Oral corticosteroids (= 10 mg/day prednisone or equivalent) and NSAIDs (up to the maximum recommended dose) are permitted if dose stable for at least 6 weeks prior to baseline
11. Females of child-bearing potential and males with female partners of child-bearing potential may participate in this trial only if using a reliable means of contraception (e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD).
12. Must be willing to receive oral folate.
13. If female and of childbearing potential, the patient must have a negative urine
pregnancy test within three weeks prior to baseline.
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
General:
1. Major surgery (including joint surgery) within eight weeks prior to screening or
planned major surgery within six months following randomization.
2. Rheumatic autoimmune disease other than RA, including SLE, MCTD, scleroderma,
polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis,
pulmonary fibrosis or Felty’s syndrome.) Sjögren’s Syndrome with RA is allowable.
3. Functional class IV as defined by the ACR Classification of Functional Status in
Rheumatoid Arthritis.
4. Prior history of or current inflammatory joint disease other than RA (e.g., gout,
reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease).
Excluded Previous or Concomitant Therapy:
5. Unsuccessful treatment with an anti-TNF agent (i.e. significant safety issues or lack of efficacy. Patients who terminated previous anti-TNF treatment due to cost or
discomfort with the subcutaneous injections, may participate in this study) (see
Inclusion #4 for anti-TNF agent washouts.)
6. Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug,
whichever is longer) of screening.
7. Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20).
8. Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within six months of baseline.
9. Intra-articular or parenteral corticosteroids within six weeks prior to baseline.
10. Immunization with a live/attenuated vaccine within four weeks prior to baseline.
11. Previous treatment with MRA (an exception to this criterion may be granted for
single dose exposure upon application to the sponsor on a case by case basis).
12. Any previous treatment with alkylating agents such as cyclophosphamide or
chlorambucil, or with total lymphoid irradiation.
Exclusions for General Safety:
13. History of severe allergic or anaphylactic reactions to human, humanized or murine
monoclonal antibodies.
14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system,
pulmonary (incl. obstructive pulmonary disease), renal, hepatic, endocrine (incl.
uncontrolled diabetes mellitus) or gastrointestinal disease.
15. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids.
16. Current liver disease as determined by principal investigator. (Patients with prior
history of ALT elevation will not be excluded.)
17. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, clinically significant abnormalities an chest X-ray as determined by the investigator, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within four weeks of screening or oral antibiotics within two weeks prior to screening.
18. Primary or secondary immunodeficiency (history of or currently active).
19. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including solid tumors and hematologic malignancies, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years.
20. Pregnant women or nursing (breas
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method