Rheumatoid arthritis
Conditions
Interventions
This investigation is a placebo-controlled randomized double blinded single-center phase IIa study, administering subcutaneously every four weeks 300 mg of monoclonal anti-IgE antibody or placebo in p
Sponsors
Leiden University Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with refractory active rheumatoid arthritis (RA). Refractory disease is defined as persistent or relapsed disease activity despite conventional treatment, i.e. combination of disease modifying antirheumatic drugs including maximal tolerable doses of methotrexate. Active disease is defined as a DAS44 (Disease Activity Score of 44 joints) score of more than 3.6; 2. Presence of IgE-ACPA; 3. Age above 18 years; 4. WHO performance status 0, 1 or 2; 5. Informed consent according to rules and regulations of Leiden University Medical Center.
Exclusion criteria
Exclusion criteria: 1. History of allergic or anaphylactic reaction to any therapeutic agent or known hypersensitivity to any component of anti-IgE monoclonal antibodies or to murine proteins; 2. No previous therapy with corticosteroids or a biological agent during the last 3 months; 3. No previous therapy with rituximab, leflunomide; 4. Life expectation of less than 6 months; 5. History of severe CNS disturbances and psychiatric problems; 6. Severe uncontrolled infections including parasitosis; 7. Irreversible major organ dysfunction, defined by any of the following criteria: A. Creatinine clearance 6.7 kPa (>50 mmHg); E. Sustained 3-fold increase in serum transaminase or bilirubin. 8. HIV positivity; 9. Positive pregnancy test or unwillingness to use adequate contraception for the duration of the study; 10. History of cancer, including solid tumors, hematological malignancies and carcinoma in situ (except for basal cell and squamous cell carcinoma of the skin that have been treated and cured).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Clinical parameters for disease activity are measured by the DAS44 (Disease Activity Score on 44 joints) assessment. Responses are classified as follows: A. Complete response is defined as a DAS44 improvement of > 1.2 and DAS2.4 or DAS 44 improvement of >0.6 en 0.6 en 3.7 or improvement of <=0.6. 2. Immunological parameters in peripheral blood and synovium after treatment with anti-IgE antibodies (omalizumab) are: A. Proportion of peripheral blood basophils, mast cells in synovium; B. Functional presence of IgE-ACPA; C. IgE , FcERI expression on basophils, mast cells, B cells and DC; D. Synovial infiltration of B cells, plasmacells, mast cells and (IgE-)ACPA presence in synovial fluid. 3. Safety and toxicity parameters are evaluated according to WHO Common Toxicity Criteria. | — |
Contacts
Public ContactA.J.M. Schuerwegh
Leiden University Medical Center (LUMC)
Outcome results
None listed