Rheumatoid arthritis
Conditions
Interventions
Weekly MTX and short-term treatment of glucocorticoids as standard of care.
KLH
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Signed informed consent prior to any study-mandated procedure; 2. Recently diagnosed treatment naïve rheumatoid arthritis patient (male or female) fulfilling to the ACR2010 criteria that are starting methotrexate therapy (with or without corticosteroids). 3. Patient must be between 18 and 75 (inclusive) years old at screening. 4. Has the ability to communicate well with the investigator and willing to comply with the study restrictions.
Exclusion criteria
Exclusion criteria: 1. Contra-indication(s) to start methotrexate (e.g. ALT/AST >3x ULN, child wish). 2. The use of any immunosuppressive or immunomodulatory medication other than the patient*s prescribed RA treatment within less than 5 half-lives prior to study participation, if the investigator judges that it may interfere with the study objectives; 3. Any known factor, condition, or disease that might interfere with study conduct or interpretation of the results, in the opinion of the investigator. 4. Unwillingness or inability to comply with the study protocol for any other reason. 5. Participants with known previous exposure to KLH. 6. History of Schistosomiasis (infection with Schistosoma parasite); 7. Have any current and / or recurrent clinically significant skin condition at the treatment area (i.e. atopic dermatitis); including tattoos. 8. Clinically significant bleeding disorders known to interfere with hemostasis after skin biopsy and/or i.m. injection. 9. Disorders in wound healing (peripheral vascular disorders or neuropathy, history of forming keloid scars). 10. Any known significant allergic reactions (urticaria or anaphylaxis) against shellfish.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Pharmacodynamic endpoints: o In vivo immune challenge (KLH): * Anti-KLH IgG and IgM in serum. * Skin biopsy: IHC staining of immune cells and RNA sequencing. * Skin blood perfusion with LSCI, erythema with multispectral imaging (Antera 3D) after intradermal KLH re-challenge. o Ex vivo immunomonitoring: * Production of cytokines after PHA stimulation, including but not limited to IFNγ, IL1b, IL2, IL6, IL8, IL17. * Inflammatory gene expression after PHA stimulation. * KLH-specific T cell response. o Flow cytometry * Characterization of monocytes, and T and B cell subsets by flow cytometry • Pharmacokinetic endpoints: o MTX-PG concentrations in erythrocytes and PBMCs over time. o Non-compartmental analysis of the PMBC and erythrocytes concentration-time data: AUC0-8m, Cmax (dose-normalized), Tmax. • Clinical endpoints: o DAS44 0.6 at 3 months o DAS44 | — |
Secondary
| Measure | Time frame |
|---|---|
| N.a. | — |
Countries
Netherlands
Outcome results
None listed