Pre-clinical RA patients with a high risk on developing the disease.
Conditions
Interventions
Trade Name: MabThera 500 mg (10mg/ml)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
CAS Number: 174722-31
Concentration unit: mg milligram(s)
Concentration
Sponsors
Division of Clinically Immunology and Rheumatology, AMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with pre-clinical RA, defined by the presence of arthralgia and at least one of the following features: ¦ IgM-rheumatoid factor (IgM-RF) of > 12.5 IU/ml ¦ anti-citrullinated peptide antibodies (ACPA) in the serum of > 25 IU/ml and at least one of the following features: ¦ CRP > 3 mg/l ¦ ESR > 28 mm/h ¦ Subclinical synovitis as assessed by ultrasound ¦ Subclinical synovitis as assessed by MRI - Age 18-80 years - Patients of reproductive potential (males and females) must use a reliable means of contraception (e.g. contraceptive pill, IUD, physical barrier) until one year after the last infusion of rituximab or the entire duration that the patient is B-cell depleted, whichever is longer. - Able and willing to give written informed consent and comply with the requirements of the study protocol. 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
Exclusion criteria: - Clinically evident arthritis, as assessed by a rheumatologist and/or a research physician. - History of arthritis, as assessed by a rheumatologist. - History or current use of DMARDs or biologicals - Previous treatment with any cell depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19) - Presence of any disease for which patient needs chronic or intermittent immunosuppressive therapy (e.g. prednisolon for COPD) - Previous treatment within 6 months with intravenous gamma globulin - History of (oral or) parenteral corticosteroid use within 4 weeks prior to inclusion - Receipt of a live vaccine within 4 weeks prior to randomization - History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies - Significant cardiac or pulmonary disease (including obstructive pulmonary disease) - Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders - Known active bacterial, viral, fungal, mycobacterial or other infection (including tuberculosis, or 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 recurrent significant infection or history of recurrent bacterial infections - Primary or secondary immunodeficiency (history of, or currently active) - History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that has been excised and cured) - Pregnant women or nursing (breast feeding) mothers - History of alcohol, drug or chemical abuse within 6 months prior to screening - Patients with poor peripheral venous access - AST or ALT > 2.5 times upper limit of normal - Platelet count less than 100 x 109/l - A white cell count less than 3.5 x 109/l - Hemoglobin of less than 5.3 mmol/l - Positive tests for hepatitis B surface antigen or hepatitis C antibody or HIV - Levels of IgG and/or IgM below 5.65 and 0.55 mg/mL respectively
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Percentage of patients developing arthritis in the treatment compared to the placebo group. The primary outcome measure is defined by the time to occurrence of clinical arthritis.;Main Objective: To study if rituximab delays/prevents the development of arthritis in patients with pre-clinical RA, defined by the presence of arthralgia with an elevated level of IgM-rheumatoid factor (IgM-RF) and/or anti-citrullinated peptide antibodies (ACPA) in the serum, and at least one of the following features: CRP > 3 mg/l, ESR > 28 mm/h, subclinical synovitis assessed by ultrasound, subclinical synovitis assessed by MRI, but no clinical signs of arthritis.;Secondary Objective: To determine if prevention of RA by a single course of rituximab is cost-effective and safe. To study the effects of rituximab in patients with pre-clinical RA on joint destruction, disability, and loss of quality of life. To explore the pharmacodynamics of rituximab in this patient population (including the duration of B cell depletion and the effects on different B cell populations, immunoglobulins, IgM-RF and ACPA levels). | — |
Countries
Netherlands
Outcome results
None listed