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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT04120831
Date of registration: 04/10/2019
Prospective Registration: Yes
Primary sponsor: University of Erlangen-N├╝rnberg Medical School
Public title: TOLERA: Tolerance Enhancement in RA TOLERA
Scientific title: Sequential B Cell/T Cell Therapy to Re-induce Humoral Immune TOLErance in ACPA- Positive Rheumatoid Arthritis A Prospective, Randomized Controlled Open Label Single-centre Clinical Trial in Adult Subjects With Active ACPA-positive Rheumatoid Arthritis Failing Methotrexate
Date of first enrolment: October 7, 2019
Target sample size: 20
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT04120831
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).  
Phase:  Phase 2
Countries of recruitment
Germany
Contacts
Name:     Arnd Kleyer, MD
Address: 
Telephone: 0049 9131 85 32093
Email: arnd.kleyer@uk-erlangen.de
Affiliation: 
Key inclusion & exclusion criteria

Main inclusion criteria:

Patients eligible for inclusion in this study have to fulfil all of the following criteria:

1. Understand and voluntarily sign an informed consent form

2. Male or female, age = 18 years at time of consent

3. Able to adhere to the study visits and protocol

4. Satisfy the ACR-EULAR criteria of Rheumatoid Arthritis at diagnosis

5. SDAI=11 at Screening

6. ACPA positive (anti CCP2 antibody compulsory at screening) (+/- rheumatoid factor)(=
40 RE/ml for CCP2 )

7. Completed vaccination for pneumococcus pneumoniae according to local guidelines at
Baseline

8. 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.

9. 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).

10. Only simultaneous therapy with Methotrexate

11. Maximum Glucocorticoid dose at Baseline: 20mg Prednisolone equivalent daily

12. JC-Virus antibody IgG and IgM in Serum negative at screening

Main exclusion criteria:

13. Planned or ongoing pregnancy status or breast-feeding

14. Ongoing or previously treatment with Abatacept or Rituximab

15. Hypersensitivity to the active substance, mouse proteins (Rituximab), chinese hamster
ovary cells (Abatacept) or other components

16. Use of any other biologic immunomodulatory agent (monoclonal antibody) except insulin.

17. 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)

18. 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.

19. 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

20. 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)

21. Patients with weakened immune system defined as diagnosis of CVID, HIV and or total
IgG levels lower than 600 mg/dl)

22. Requirement for immunization with live vaccine during the study period or within 4
weeks preceding baseline.

23. Contraindication for Rituximab or Abatacept treatment according to their SmPCs



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
Intervention(s)
Drug: Abatacept Injection
Primary Outcome(s)
Primary endpoint [Time Frame: week 52]
Secondary Outcome(s)
secondary endpoints [Time Frame: week 52]
Secondary ID(s)
IM101-817
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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