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Inhibition of Co-Stimulation in Rheumatoid Arthritis (ICoSRA)

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ClinicalTrials.gov Identifier: NCT02652273
Recruitment Status : Unknown
Verified January 2016 by NHS Greater Glasgow and Clyde.
Recruitment status was:  Not yet recruiting
First Posted : January 11, 2016
Last Update Posted : January 12, 2016
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Abatacept Phase 4

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Inhibition of Co-Stimulation in Rheumatoid Arthritis
Study Start Date : January 2016
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Abatacept

Arm Intervention/treatment
Experimental: Abatacept
Abatacept 125mg administered via subcutaneous injection once a week for 24 weeks
Drug: Abatacept
Abatacept 125mg/ml




Primary Outcome Measures :
  1. Immunological response [ Time Frame: Baseline and 12 weeks ]
    Change in T cell immune response to citrullinated peptides following costimulatory modulation


Secondary Outcome Measures :
  1. Immunological response [ Time Frame: Baseline, 4, 12 and 24 weeks ]
    Change in immunological response from baseline, as measured by transcriptional profile of relevant cell subset

  2. Clinical response American College of Rheumatology (ACR) 20 [ Time Frame: Baseline and 24 weeks ]
    Change in ACR 20 from baseline

  3. Clinical response Disease Activity Score (DAS)28 [ Time Frame: Baseline and 24 weeks ]
    Change in DAS 28 from baseline

  4. T cell profile [ Time Frame: Baseline, 12 and 24 weeks ]
    Change in T cell subpopulation profile from baseline

  5. T cell response [ Time Frame: 24 weeks ]
    Antigen-specific T cell response to tetanus

  6. DC (CD11c+) phenotype [ Time Frame: 24 weeks ]
    Dendritic cell (DC) (CD11c+) phenotype as measured by major histocompatibility complex (MHC) II expression

  7. Biomarkers [ Time Frame: 24 weeks ]
    Preliminary identification of biomarkers of response using urinary metabol/proteomic analysis



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02652273


Contacts
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Contact: Iain McInnes, Prof +44 (0)141 330 8412 iain.mcinnes@glasgow.ac.uk
Contact: Stefan Siebert, Dr +44 (0) 141 330 3375 stefan.siebert@glasgow.ac.uk

Locations
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United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust Not yet recruiting
Newcastle upon Tyne, United Kingdom
Sponsors and Collaborators
NHS Greater Glasgow and Clyde
University of Glasgow
Investigators
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Principal Investigator: Iain McInnes, Prof University of Glasgow

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Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT02652273     History of Changes
Other Study ID Numbers: GN13RH410
2014-004419-35 ( EudraCT Number )
First Posted: January 11, 2016    Key Record Dates
Last Update Posted: January 12, 2016
Last Verified: January 2016

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents