Efficacy of Rituximab treatment in patients with rheumatoid arthritis having inadequate response to TNF blocker
- Conditions
- To investigate the efficacy of treatment with Rituximab (MabThera®) in patients with active RA whose current treatment with one or more TNF-blocker (Etanercept - Enbrel®, Infliximab – Remicade® or Adalimumab - Humira®) alone or in combination with MTX is insufficient measured by DAS28 activity index.
- Registration Number
- EUCTR2006-004673-98-HU
- Lead Sponsor
- Roche (Hungary) Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
•Women or men 18 years of age or older
•Diagnosis of RA according to the revised 1987 criteria of the ARA for at least 3 months prior to first administration of study medication
•Inadequate response or intolerance to one or more anti-TNF-therapies alone or in combination with MTX
•Wash out period for anti-TNF therapies: 4 weeks for etanercept, 8 weeks for infliximab and for adalimumab
•Active disease at the time of screening as defined by:
- = 6 swollen on a 66/68 joint count
- = 6 tender joints on a 66/68 joint count
•And one out of the following 3 categories:
- ESR = 28 mm/ h
- CRP = 1.5 mg/ dl
- Morning stiffness = 45 min
•And one out of the following 2 categories:
-Anti-cyclic citrullinated peptide (Anti-CCP) antibody-positive
-Rheumatoid factor (RF)-positive at screening
•If using NSAIDs or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent.
•If using oral corticosteroids, must be on a stable dose equivalent to = 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent. If currently not using corticosteroids, the subject must not have received oral corticosteroids for at least 2 weeks prior to first administration of study medication.
•Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study agent.
•Female subjects of childbearing potential must test negative for pregnancy. A pregnancy test will be performed at the beginning and at the end of the study.
•The screening laboratory test must meet the following criteria:
- Hemoglobin = 8.5 g/ dl providing the low hemoglobin level is not due to other diseases than anemia of chronic inflammation.
- WBC = 3500 / µl
- Neutrophils = 1500 / µl
- Platelets = 100 000 / µl
- Serum transaminase = 2 times the upper limit of normal
- Serum creatinine = 1.7 mg/ dl
•The patient must be able to adhere the study visit schedule and other protocol requirements and must have given informed consent prior to any screening procedures.
•Patients who, in the opinion of the investigator, are able to understand and complete the questionnaires, are willing and able to comply with the protocol requirements;
•Patients who have signed the informed consent
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
•Pregnant women, nursing mothers or a planned pregnancy within six months after last scheduled treatment.
•Patients with other inflammatory diseases that might interfere with the evaluation of the RA.
•Severe heart failure ( NYHA class IV) or severe, uncontrolled cardiac disease
•Patients with fibromyalgia syndrome.
•Use of IM, IV, IA cortocisteroids within 4 weeks prior to screening.
•Treatment with any investigational drug within 3 months prior to screening.
•A history of known allergy to murine proteins, e.g. allergy to Infliximab.
•History of infected joint prothesis within the previous 5 years.
•Chronic infections.
•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).
•Current signs or symptoms of other severe uncontrolled disease which in the investigators opinion would put the patient at an unacceptable risk.
•History of lymphoproliferative disease, any current malignancies or history of malignancy within 5 years other than successfully treated basal cell carcinoma or squamous cell carcinoma of the skin.
•History of drug abuse.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate the efficacy of treatment with Rituximab (MabThera®) in patients with active RA whose current treatment with one or more TNF-blocker (Etanercept - Enbrel®, Infliximab – Remicade® or Adalimumab - Humira®) alone or in combination with MTX is insufficient measured by DAS28 activity index.;Secondary Objective: •The ACR response criteria (20%, 50%, 70%)<br>•HAQ <br>•Laboratory assessments (ESR, CRP, CBC and routine blood chemistry albumine, creatinine, blood urea nitrogen, serum electrolites, ALAT, ASAT and urine analysis will be performed<br>•Autoantibodies assessments (Anti-cyclic citrullinated peptide (Anti-CCP), Rheumatoid Factor<br>•Serum VEGF level assessment<br>•Safety assessments, adverse events<br>;Primary end point(s): DAS 28 Assessments <br>measure will be the frequency of reaching low disease activity or remission as measured by the DAS28<3,2 at 24 weeks.<br>
- Secondary Outcome Measures
Name Time Method