Inhibition of Co-Stimulation in Rheumatoid Arthritis

NCT ID: NCT02652273

Last Updated: 2016-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2019-01-31

Brief Summary

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The purpose of this study is to use abatacept as a clinical molecular probe to evaluate the effects of inhibiting costimulation on immune responses in patients with rheumatoid arthritis (RA).

Detailed Description

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Rheumatoid arthritis (RA) is a chronic inflammatory immune mediated arthritis which leads to pain, swelling and destruction of joints. RA affects more than 500,000 subjects in the United Kingdom (UK) and incurs significant health and economic cost. Most patients require potent immune suppressing drugs such as methotrexate, which help reduce pain and stiffness, and protect the joints against damage. However, many patients do not respond or are unable to tolerate methotrexate. In these patients, biologic drugs such as abatacept are used to try to control the arthritis.

Abatacept is designed to target and inhibit a specific molecule involved in "costimulation" of the inflammatory signal that is thought to be important in RA. While abatacept has been shown to be effective in trials and clinical practice, the exact mechanism of action of abatacept in RA has not been fully elucidated. Understanding these actions is likely to inform both the use of abatacept in RA and lead to increased understanding of inflammation in humans with implications for further therapies. This six month prospective open label study, therefore, aims to investigate the effects of inhibiting costimulation on a variety of important inflammatory cell types and processes in humans with RA.

25 participants with RA who have bad prognostic genetic markers (Anti-citrullinated protein antibodies (ACPA) and human leukocyte antigen (HLADR4) and who were scheduled to receive subcutaneous abatacept as part of their standard clinical treatment will be recruited. Consenting participants will followed for a total of 24 weeks during which time they will have additional venous blood and urine samples taken to investigate the effects of abatacept on their immune cells and system. The primary endpoint of the study is the characterisation of the immune response following costimulatory modulation in RA patients at 12 weeks. Secondary endpoints include change in immunological response and its association with clinical outcome measures up to 24 weeks.

Conditions

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Arthritis, Rheumatoid

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Abatacept

Abatacept 125mg administered via subcutaneous injection once a week for 24 weeks

Group Type EXPERIMENTAL

Abatacept

Intervention Type DRUG

Abatacept 125mg/ml

Interventions

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Abatacept

Abatacept 125mg/ml

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* RA as defined by the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
* Eligible for abatacept therapy according to local/national guidelines

* Active RA defined by DAS28 score required by local guidelines for eligibility for abatacept
* Have previously failed (efficacy or tolerance) at least one disease-modifying antirheumatic drug (DMARD)
* Have no contraindications to treatment with abatacept
* Be able to tolerate methotrexate at dose of 10-25mg/week, either orally or subcutaneously
* Anti-cyclic citrullinated peptide (CCP) positive
* Human leukocyte antigen D related (HLA-DR) B1\*0401 or 0404) positive
* Able and willing to give written informed consent and comply with the requirements of the study protocol

Exclusion Criteria

* History of or current autoimmune rheumatic disease other than RA
* Concomitant use of any biologic agent, including tumor necrosis factor (TNF) inhibitors
* Previous abatacept treatment
* Patients requiring \>10mg prednisolone daily or intramuscular (IM) corticosteroids
* Active infection
* Known HIV or hepatitis B/C infection
* Latent tuberculosis (TB) infection
* Malignancy (other than non-melanoma skin cell cancers) within 5 years
* Women who are pregnant, women of childbearing potential who are unwilling to use appropriate contraception or breast-feeding
* Inability to give informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Glasgow

OTHER

Sponsor Role collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Iain McInnes, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Locations

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NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United Kingdom

Central Contacts

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Iain McInnes, Prof

Role: CONTACT

+44 (0)141 330 8412

Stefan Siebert, Dr

Role: CONTACT

+44 (0) 141 330 3375

Other Identifiers

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2014-004419-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GN13RH410

Identifier Type: -

Identifier Source: org_study_id

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