Rheumatoid Arthritis: patients who are dual ACPA and HLA-DR4 positive MedDRA version: 21.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Abatacept
Product Name: Abatacept
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Abatacept
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, aged > 18 years, 2. RA as defined by the 2010 EULAR/ACR classification criteria 3. Eligible for abatacept therapy according to local/national guidelines: a. Active RA defined by DAS28 score required by local guidelines for eligibility for abatacept b. Have previously failed (efficacy or tolerance) at least one DMARDs c. Have no contraindications to treatment with abatacept 4. Be able to tolerate methotrexate at dose of 10-25mg/week, either orally or subcutaneously 5. Anti-CCP positive 6. HLA-DRB1*0401 or 0404 positive 7. Able and willing to give written informed consent and comply with the requirements of the study protocol. Note: During screening, only patients who are HLA-DRB1*0401/0404 positive will proceed with the study, while DRB1*0401/0404 negative patients will be withdrawn from the study. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • History of or current autoimmune rheumatic disease other than RA • Concomitant use of any biologic agent, including TNF inhibitors • Previous abatacept treatment • Patients requiring >10mg prednisolone daily or IM corticosteroids • Active infection. • Known HIV or hepatitis B/C infection • Latent TB infection • Malignancy (other than non-melanoma skin cell cancers) within 5 years • Women who are pregnant, women of child bearing potential who are unwilling to use appropriate contraception or breast-feeding • Inability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to characterize the impact of inhibition of costimulation (with abatacept) on the T cell mediated autoimmune response in ACPA+ RA patients. ; Secondary Objective: The secondary goals are to: (i) identify biomarkers for response to costimulatory blockade in RA (ii) characterise the impact of abatacept on the phenotype and function of myeloid and dendritic cells in RA (iii) to correlate the foregoing with the changes observed in clinical parameters of disease. ;Primary end point(s): Change of the immunological phenotype in T cells following costimulatory blockade for 12 weeks compared with pre-therapy baseline.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Changes in immunological response at 4, 12 and 24 weeks measured by transcriptional profiling of relevant cell subsets. 2) Association of immunological responses with clinical outcome measures (including ACR20, DAS28) up to 24 weeks 3) T cell subpopulation profiles(e.g. Th1, Th2, Th17, Tregs and TFH; CD28, CD40L, ICOS, PD-1 profiles) at 12 and 24 weeks 4) Effects on broader antigen-specific T cell / B cell responses (including response to recall antigens such as tetanus and measurement of autoantibodies) 5) Impact on DC (CD11c+) phenotype, including MHC II expression 6) Epigenetic alterations that occur in cell subsets between base line and wk 24 (including microRNAs) 7) Preliminary biomarkers of response identified using urinary metabolomic and/or proteomic analysis. ; Timepoint(s) of evaluation of this end point: 1) 4, 12 and 24 weeks 2) up to 24 weeks 3) 12 and 24 weeks 4) 4, 12 and 24 weeks 5) 4, 12 and 24 weeks 6) 24 weeks 7) 12 and 24 weeks | — |
Countries
United Kingdom
Contacts
Public ContactJurgen Van Melckebeke
NHS Greater Glasgow and Clyde
Outcome results
None listed