Januse kinase Inhibition with Filgotinib to Silence Autoreactive B cells in Rheumatoid Arthritis
- Conditions
- Rheumatoid arthritis10023213
- Registration Number
- NL-OMON53878
- Lead Sponsor
- eids Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 40
In order to be eligible to participate in this study, a subject must meet all
of the following criteria. Each patient must:
- have a diagnosis of RA and must have fulfilled the revised 2010 EULAR/ACR
criteria for classification of RA prior to initiation of first-line treatment.
- have a positive test for the presence of anti-citrullinated protein
antibodies (ACPA) in serum with a value of at least 200 U/ml, as determined by
routine clinical assay.
- have moderate to highly active disease defined by a disease activity score
evaluating 28 joints (DAS28) >= 3.2 or, correspondingly, an sDAI score of > 11.
- have used methotrexate therapy at a maximally tolerated dose once weekly for
at least 1 month; concomitant glucocorticoid therapy is allowed if at a stable
dose of <= 7.5 mg prednisolon equivalent within 30 days prior to entry in the
study.
- have adequate hematologic function (ANC >= 4000 cells/µL, platelet count >=
150000/µL, and haemoglobin >= 10 g/dL (corresponding to 6.2 mmol/L)
- have a serum creatinine clearance of >15 ml/min
- be at least 18 years of age
- if female and of childbearing potential, agree to: comply with effective
contraceptive measures, use adequate contraception since the last menses and
use adequate contraception during the study
- be willing to undergo pre-treatment screening for latent tuberculosis
infection by chest X-ray and Mantoux testing as well as serological screening
for chronic viral hepatitis infection. As an alternative for the Mantoux test,
a standardized IFN-gamma release assay may be used to assess latent
tuberculosis infection.
- be able and willing to give written informed consent prior to entry in the
study.
A potential subject who meets any of the following criteria will be excluded
from participation in this study. Any patient who:
- has ever been treated with rituximab or another B-cell depleting agent
- has been treated with a biological DMARD (except rituximab) or a targeted
synthetic DMARD within 3 months prior to entry in the study
- has received intra-articular or systemic glucocorticoid injections within 30
days prior to baseline or requires narcotic analgesics other than those
accepted by the investigator for analgesia (e.g. paracetamol, NSAIDs, codeine,
tramadol)
* has been tested negative for ACPA
* is in clinical remission as defined by a disease activity score evaluating 28
joints (DAS28) <= 2.6 or, correspondingly, an sDAI <= 3.3
* has evidence of a medical condition which represents a contra-indication for
initiation of either a TNF-alpha inhibitor or a Janus kinase inhibitor, as
outlined in the most recent SPCs of either adalimumab and/or Filgotinib.
* has liver function abnormality (AST and/or ALT >= 3 x upper limit of normal
range)
* has concurrent treatment with an experimental drug or who has participated in
another clinical trial with an investigational drug within 30 days prior to
study entry
* has past or current history of solid or haematological neoplasms, except for
curatively treated non-melanoma skin cancer, adequately treated in situ
carcinoma of the cervix or another cancer curatively treated and with no
evidence of disease for at least 10 years
* is pregnant or a currently nursing woman
* is, female and of childbearing potential, unwilling to use adequate
contraceptive measures during the study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the change from baseline in the frequency of<br /><br>ACPA-expressing B cells secreting ACPA-IgG in ex-vivo PBMC cultures at the 24<br /><br>week time-point compared between the two treatment arms.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are designed to define the changes to the<br /><br>auto-reactive B cell compartment induced by filgotinib versus control treatment<br /><br>in relation to the clinical context and to define/elucidate the mode of action<br /><br>of filgotinib with regard to these changes. </p><br>