Inhibition of Co-Stimulation in Rheumatoid Arthritis

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2014-004419-35-GB
• Lead Sponsor: HS Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-02
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 25

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who are HLA-DRB1*0401/0404 positive will proceed with the study, while DRB1*0401/0404 negative patients will be withdrawn from the study.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

• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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. ;<br> Secondary Objective: The secondary goals are to:<br> (i) identify biomarkers for response to costimulatory blockade in RA<br> (ii) characterise the impact of abatacept on the phenotype and function of myeloid and dendritic cells in RA<br> (iii) to correlate the foregoing with the changes observed in clinical parameters of disease.<br> ;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