Th17 Responses Evaluated in RA Patients on Inhibitors of TNFα

NCT02620189 | Completed DMC

• 1 other identifier: 009745
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 8

Brief Summary

Preliminary data suggest that up-regulation of Interleukin -17 (IL-17) and the T-helper 17 (Th17) pathway occurs in rheumatoid arthritis (RA) patients on anti-Tumour Necrosis Factor (TNF) therapy who demonstrated an incomplete clinical response. A deeper understanding of this is required in order to determine whether IL-17 or the Th17 pathway is a valid target for intervention in this population to improve response outcome. The study objective is to observe biologic naïve RA subjects on anti-TNF therapies and take measurements of peripheral blood and synovial tissue to assess differences in the IL-17 and Th17 pathways between responders and non-responders. The aim of the study is to test if increased Th17 pathway activity is present in subjects who do not respond clinically to anti-TNF therapy. Clinical assessments, synovial bio-markers and ultrasound will be used as determinants of clinical response. The study may identify disease characteristics that determine which subjects may be more likely to respond to anti-TNF therapy, or those who may require either a different treatment option, or additional pathway inhibition in addition to TNF, in order to achieve clinical response.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Measure change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline

  Change in clinical response using Disease Activity Score DAS28 (C-Reactive Protein) at week 24 compared to baseline

  Baseline and week 24

Secondary Outcomes (1)

• Change in Interleukin (IL)-17/T helper (Th)17 pathway activity in responders and non-responders to anti-Tumour Necrosis Factor (TNF) therapy

  Baseline and week 24

Interventions

Anti-TNF Biologics Therapy DRUG

Also known as: Etanercept (Enbrel), Adalimumab (Humira), Certolizumab Pegol(Cimzia)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects who fulfil the NICE guidelines for biologic anti-TNF therapy as their first line treatment following failure of standard disease modifying anti-rheumatic therapy will be recruited from various secondary care settings at a number of centres throughout the UK.

You may qualify if:

• Men and women ≥ 18 years of age
• An RA diagnosis as defined by the 2010 revised EULAR/ACR classification criteria.
• Subjects who fulfil the NICE guidelines for Biologic therapy as their first line treatment following failure of standard disease modifying anti-rheumatic therapy.
• Subjects may be on cDMARDs (or MTX monotherapy) one of which must be MTX. Participants should be receiving MTX for at least 2 months at a stable dose of 7.5-25 mg/week before Week 0 visit.
• Subjects may be on oral steroids (prednisone ≤10 mg/day, or equivalent corticosteroid) with a stable dose for the 4 weeks prior to Week 0 visit.
• Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study.
• Participants must be able to adhere to the study visit schedule.
• The participant must be capable of giving informed consent and the consent must be obtained prior to any screening procedures.
• Must have a chest X-ray within 6 months prior to commencement of anti-TNF therapy with no evidence of malignancy, infection or fibrosis.

You may not qualify if:

• Participants will be excluded from this study for any of the following reasons:
• Women who are pregnant or breast feeding.
• Previous use of Rheumatoid Arthritis anti-TNF biologics, or ANY other type of biologic therapy or Investigational Medicinal Product.
• Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening.
• Known HIV, Hepatitis B, or Hepatitis C infection.
• Have active TB or have evidence of latent TB (old or latent TB on chest x-ray, without adequate therapy for TB initiated prior to first dose of study drug). Participants with a current close contact with an individual with active TB and participants who have completed treatment for active TB within the previous 2 years are explicitly excluded from the trial. Participants with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrolment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies.
• Presence of a transplanted organ (with the exception of a corneal transplant \>3 months prior to screening).
• Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence).
• History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
• Known recent substance abuse (drug or alcohol).
• Poor tolerability of venepuncture required blood sampling during the study period.
• Planning to have surgery for RA or other significant surgery during the period of the study.

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (8)

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Barts Health NHS Trust, Experimental Medicine & Rheumatology, Mile End Hospital

London, E1 4DG, United Kingdom

Location

Barts Health NHS Trust,Department of Rheumatology,Whipps Cross University Hospital

London, E11 1NR, United Kingdom

Location

University College London Hospitals NHS Foundation Trust, Rheumatology Department

London, NW1 2PG, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust, The Kellgren Centre for Rheumatology

Manchester, M13 9WL, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary

Newcastle, NE1 4LP, United Kingdom

Location

Oxford University Hospitals NHS Trust, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences

Oxford, OX3 7LD, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

* Synovial tissue * RNA extraction on peripheral blood mononuclear cells

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Etanercept; Adalimumab; Certolizumab Pegol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments

Study Officials

• Costantino Pitzalis, MD PhD FRCP

  Queen Mary University of London

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: December 2, 2015
• Study Start: March 1, 2015
• Primary Completion: May 24, 2017
• Study Completion: May 24, 2017
• Last Updated: September 26, 2022

Record last verified: 2015-11

Locations

GB (8)