Inhibition of Co-Stimulation in Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2014-004419-35-GB
• Date of registration: 02/02/2015
• Prospective Registration: Yes
• Primary sponsor: NHS Greater Glasgow and Clyde
• Public title: Inhibition of Co-Stimulation in Rheumatoid Arthritis
• Scientific title: Inhibition of Co-Stimulation in Rheumatoid Arthritis - Inhibition of Co-Stimulation in Rheumatoid Arthritis (ICoSRA)
• Date of first enrolment: 18/03/2015
• Target sample size: 25
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004419-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Jurgen Van Melckebeke
• Affiliation: NHS Greater Glasgow and Clyde

• Name: Jurgen Van Melckebeke
• Affiliation: NHS Greater Glasgow and Clyde

Key inclusion & exclusion 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who are HLA-DRB1*0401/0404 positive will proceed with the study, while DRB1*0401/0404 negative patients will be withdrawn from the study.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:
• 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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]

Intervention(s)

Trade Name: Abatacept
Product Name: Abatacept
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Abatacept
CAS Number: 332348-12-6
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 125-

Primary Outcome(s)

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.

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.

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

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

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.

Secondary ID(s)

GN13RH410

Source(s) of Monetary Support

Bristol Myers Squibb

Secondary Sponsor(s)

University of Glasgow

Ethics review

Status: Approved
Approval date: 18/03/2015
Contact: