Active reumathoid arthritis
Conditions
Interventions
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:
Sponsors
Roche AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Ages 18-80 years, inclusive. 3. Patients with documented moderate to severe active rheumatoid arthritis at screening as follows: • tender joint count = 6 (28 joint count) • swollen joint count = 6 (28 joint count) • C-reactive protein (CRP) or Erythrocyte sedimentation rate (ESR) levels elevated above the upper limit of normal (as per local laboratory), or morning stiffness lasting =30 minutes. 4. Patients who are to receive, or who are currently receiving treatment for RA on an outpatient basis. 5. Documented inadequate response to a single previous or current treatment with the anti–TNF–alfa agents etanercept, infliximab, or adalimumab because of toxicity or inadequate efficacy (inadequate efficacy requires treatment with etanercept for >= 3 months at 25 mg twice a week or 50 mg weekly; or at least 3 infusions of infliximab at >= 3 mg/kg; or adalimumab for >= 3 months at 40 mg every other week). 6. Must have received MTX at a dose of 10-25 mg/week (p.o. or parenteral) for at least 12 weeks prior to screening, at a stable dose over the last 4 weeks prior to day 1. 7. Corticosteroids (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria Related to RA 1. Patients with severe rheumatoid arthritis (functional class IV as defined by the ACR Classification of Functional Status in RA) that requires either a wheelchair or results in the patient being bed bound. 2. Bone/joint surgery within 8 weeks prior to day 1, or joint surgery planned within 48 weeks of day 1. Exclusions Related to Medications 1. History of severe allergic or anaphylactic reactions to monoclonal antibodies 2. Previous treatment with rituximab (Rituxan/Mabthera). 3. Use of an anti–TNF–alfa agent within 8 weeks of Day 1 (or 4 weeks in the case of etanercept). 4. Concurrent treatment with any DMARD other than methotrexate. Treatment with all DMARDS must be discontinued at least 14 days prior to Day 1 except for the following: • azathioprine for =4 weeks; • etanercept for =4 weeks; • leflunomide for =8 weeks; • infliximab or adalimumab for =8 weeks 5. In the event that abatacept is approved as a treatment for RA during the course of this study, this must also be discontinued for =8 weeks prior to day 1. 6. Receipt of any vaccine within 4 weeks prior to day 1 (it is recommended that a patient’s vaccination record and the need for immunization prior to receiving rituximab should be carefully investigated). 7. Intra-articular or parenteral glucocorticoids within 4 weeks prior to day 1. 8. Treatment with any investigational agent within 4 weeks of day 1 or within 5 half-lives of the investigational drug (which ever is the longer). 9. Previous treatment with any cell-depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, anti-CD11a, anti-CD22, anti-BLys/BAFF) Exclusions for General Safety/Health 1. Evidence of any severe or significant medical condition(s) or disease(s) that, in the view of the investigator, prohibits participation in the study. 2. Significant cardiac or pulmonary disease (including obstructive pulmonary disease). 3. 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 day 1 or oral anti-infectives within 2 weeks prior to day 1. 4. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection. 5. History of serious recurrent or chronic infection. 6. Pregnancy or lactation. 7. History of cancer, including solid tumours, hematological malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured). 8. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline. Exclusions Related to Laboratory Findings 1. Hemoglobin < 9.0 g/dL. 2. Absolute neutrophil count < 1.5 x 103/µL. 3. Levels of IgG <5.0 mg/mL. 4. Levels of IgM < 0.40 mg/mL. 5. Positive tests for hepatitis B surface antigen (HBsAg) and/or positive tests for hepatitis B core antibody (HBcAb) associated with detectable hepatitis B viral DNA (HBV DNA) or hepatitis C serology. 6. Positive serum test for human chorionic gonadotropin (pregnancy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the safety of rituximab in patients with active RA who are receiving MTX and who have a previous or current inadequate response or were intolerant to treatment with one prior anti–TNF–alfa therapy.;Primary end point(s): The primary objective of this study is to evaluate the safety of rituximab in patients with active RA who are receiving MTX and who have a previous or current inadequate response or were intolerant to treatment with one prior anti–TNF–? therapy;Secondary Objective: To evaluate: To evaluate the safety of re treatment with rituximab in combination with MTX. The effectiveness of initial treatment with rituximab in combination with MTX Changes in patient reported outcomes following treatment or re treatment with rituximab. The timing of retreatment with rituximab in routine patient care The factors which influence the clinical judgment to re treat with rituximab including: • Disease Activity Score (DAS 28) • DAS, and ACR core component values • presence or absence of disease flare • additional clinical or laboratory factors influencing re treatment Further exploratory endpoints (for example complete clinical response, duration of remission) will be analyzed descriptively during the period following the Week 24 visit. Response to rituximab based on the patient’s prior historical response to anti-TNF therapy (lack of initial response, loss of response, tolerability) will also be explored. | — |
Countries
Sweden
Outcome results
None listed