Status:
UNKNOWN
TOLERA: Tolerance Enhancement in RA
Lead Sponsor:
University of Erlangen-Nürnberg Medical School
Conditions:
Rheumatoid Arthritis
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Although anti-citrullinated protein antibodies (ACPA) including anti-CCP2 antibodies are known to promote inflammation and joint destruction in patients suffering from ACPA-positive rheumatoid arthrit...
Detailed Description
Based on fact that both a B cell-targeting therapy with Rituximab and a T cell-targeting therapy with Abatacept affect ACPA levels and can occasionally induce seroconversion and an immunological remis...
Eligibility Criteria
Inclusion
- Main inclusion criteria:
- Patients eligible for inclusion in this study have to fulfil all of the following criteria:
- Understand and voluntarily sign an informed consent form
- Male or female, age ≥ 18 years at time of consent
- Able to adhere to the study visits and protocol
- Satisfy the ACR-EULAR criteria of Rheumatoid Arthritis at diagnosis
- SDAI≥11 at Screening
- ACPA positive (anti CCP2 antibody compulsory at screening) (+/- rheumatoid factor)(≥ 40 RE/ml for CCP2 )
- Completed vaccination for pneumococcus pneumoniae according to local guidelines at Baseline
- Inadequate treatment response with highest tolerated dose after 3 months therapy and/or intolerance to cDMARDs specifically Methotrexate, Sulfasalazine, Hydroxychloroquine and Leflunomide or bDMARDs specifically TNF-alpha inhibitors or IL-6 receptor blockers.
- Sulfasalazin, Hydroxychloroquine and Leflunomide must be stopped during screening phase and be replaced by Methotrexate. Leflunomide must be washed out until Baseline (Colestyramine 3x/day 8g/day for 11 days).
- Only simultaneous therapy with Methotrexate
- Maximum Glucocorticoid dose at Baseline: 20mg Prednisolone equivalent daily
- JC-Virus antibody IgG and IgM in Serum negative at screening
- Main exclusion criteria:
- Planned or ongoing pregnancy status or breast-feeding
- Ongoing or previously treatment with Abatacept or Rituximab
- Hypersensitivity to the active substance, mouse proteins (Rituximab), chinese hamster ovary cells (Abatacept) or other components
- Use of any other biologic immunomodulatory agent (monoclonal antibody) except insulin.
- Active ongoing inflammatory diseases other than RA that might confound the evaluation of the benefit of the therapy (including SLE, PSS, MCTD, SpA, Behcet disease, vasculitis or autoimmune hepatitis)
- History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test. If presence of latent tuberculosis is established then treatment according to local country guidelines must have been initiated but patient cannot take part in the study.
- Known active or past infection with hepatitis B or hepatitis C at screening or baseline as defined by Antibody positivity and/or positive DNA/RNA levels of hepatitis B/C
- Uncontrolled severe concomitant disease (including diabetes with plasma glucose \>11.1 mmol/l rsp. 200 mg/dl, heart insufficiency \>= NYHA III, COPD with severity \>= GOLD 3, asthma according to GINA classification \>= step 3)
- Patients with weakened immune system defined as diagnosis of CVID, HIV and or total IgG levels lower than 600 mg/dl)
- Requirement for immunization with live vaccine during the study period or within 4 weeks preceding baseline.
- Contraindication for Rituximab or Abatacept treatment according to their SmPCs
Exclusion
Key Trial Info
Start Date :
October 7 2019
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2022
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT04120831
Start Date
October 7 2019
End Date
December 1 2022
Last Update
October 9 2019
Active Locations (1)
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1
Universitiy Hospital Erlangen
Erlangen, Bavaria, Germany, 91052