A randomized placebo-controlled, multicenter, blinded Phase I/II study of the safety of escalating single intravenous doses of ocrelizumab (Ro 496-4913, PRO70769, rhuMAb 2H7) in patients with moderate to severe rheumatoid arthritis receiving stable doses of concomitant methotrexate but with unsatisfactory clinical response. - N/A
- Conditions
- Rheumatoid Arthritis
- Registration Number
- EUCTR2004-002132-26-GB
- Lead Sponsor
- F. Hoffmann-La Roche Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 160
Patients must meet the following criteria to be eligible for study entry:
•Ability and willingness to provide written informed consent and to comply with the requirements of the protocol
•Aged 18–80 years inclusive
Have active disease defined as:
•Diagnosis of RA for at least 6 months according to the revised 1987 ACR criteria for the classification of RA (see Study Procedures and Administrative Manual)
•Positive serum rheumatoid factor (=20 IU/L)
•Current treatment for RA on an outpatient basis
•At screening: one of the following: C-reactive protein (CRP) =1.0 mg/dL (10 mg/L)
Or
erythrocyte sedimentation rate (ESR) =28 mm/hr or morning stiffness of =45 minutes
•Swollen joint count of =8 (66 joint count) and tender joint count of =8 (68 joint count) at screening
Previous and current treatments:
•Have failed treatment (because of lack of tolerability or efficacy) with no more than six DMARDs or biologics including MTX. The following groups of DMARDS are considered as a single agent for this count:
- all forms of gold
- all forms of methotrexate
- chloroquine or hydroxychloroquine
- sulfasalazine and mesalazine
- etanercept, infliximab and adalimumab
- all other DMARDs not specified here count as a single agent
•Current treatment with MTX at a dose of 10–25 mg weekly (p.o. or parenterally) for at least 12 weeks, with the last 4 weeks prior to screening at a stable dose
•All DMARDs other than MTX should be withdrawn at least 4 weeks prior to randomization (8 weeks for etanercept, infliximab, adalimumab and leflunomide [after cholestyramine drug removal for leflunomide unless it was discontinued 12 weeks prior to treatment])
•If receiving current treatment with corticosteroids, the dose must not exceed 10 mg/day prednisone or equivalent and the last 4 weeks prior to screening must be at a stable dose
•If receiving current treatment with NSAIDs, the patient must be on stable dose for the last 2 weeks prior to screening
•Patient must be willing to receive oral folic acid
Other:
•For patients of reproductive potential (males and females), a reliable means of contraception must be used (e.g., hormonal contraceptive, intrauterine device, physical barrier)
•For females of childbearing potential (including those who have had a tubal ligation), a serum pregnancy test within 2 weeks prior to randomization must be negative.
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
Patients who meet any of the following exclusion criteria related to rheumatoid arthritis are ineligible for study entry:
•Bone or joint surgery (including joint fusion) within 8 weeks prior to screening or joint surgery planned within 24 weeks after randomization
•Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, or Felty’s syndrome); patients with Sjogren’s syndrome with RA are eligible.
•Functional Class IV as defined by the ACR classification of functional status in RA (see Study Procedures and Administrative Manual)
•History of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic rheumatic disorders (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, overlap syndrome).
Exclusion Criteria Related to Medications
Patients who meet the following criteria related to medications will be excluded:
•Concurrent treatment with any DMARD (except MTX) or any anti–TNF-a therapy or other biologic therapy
•Treatment with any investigational agent within 4 weeks of screening or five half-lives of the investigational drug (whichever is longer).
•Patients who have received previous treatment with natalizumab (Tysabri) in clinical trials are excluded, unless 12 weeks (5 half-lives) has elapsed since the last treatment, and a baseline neurologic evaluation shows no abnormalities
•Previous treatment with any cell-depleting therapies, including investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, or alefacept)
•Previous treatment within 6 months with IV ?-globulin or Prosorba® column
•Intra-articular or parenteral corticosteroids within 4 weeks prior to the screening visit
•Receipt of a live/attenuated vaccine within 4 weeks prior to screening
•Previous treatment with rituximab (MabThera®/Rituxan®) or any other anti-CD20 agent
•Intolerance or contraindications to oral or IV corticosteroids*
Exclusion Criteria Related to General Safety
The following are exclusions related to general safety:
Allergies
•History of severe allergic or anaphylactic reactions to humanized or chimeric monoclonal antibodies
Infections
•Known active bacterial, viral, fungal, mycobacterial, or other infection (including atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
•History of active tuberculosis (TB) or concurrent treatment for TB
•Positive purified protein derivative (PPD) screening test (see Study Procedures and Administrative Manual for Centers for Disease Control guidelines and definition of high risk individuals)
•History of recurrent significant infections
Other
•Primary or secondary immun
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