Stratification of biologic Therapies for Rheumatoid Arthritis by Pathobiology

Phase 1

• Conditions: Rhuematoid Arthritis; MedDRA version: 20.0Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2017-004079-30-ES
• Lead Sponsor: Joint Research & Development Office (QMUL)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-21
• Study Completion: 2021-01-23
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 223

Inclusion Criteria

Patients will be recruited with active Rheumatoid Arthritis:
1.2010 ACR / EULAR classification criteria for a diagnosis of Rheumatoid Arthritis *
2.Patients with DMARD failure and eligible for anti-TNF therapy according to UK NICE guidelines **Patients must have a minimum of 3 swollen joints – the joint selected for biopsy and a minimum of 2 from 28 joint count set, as assessed at biopsy visit
3.Selected joint for biopsy must be minimum grade 2 synovial thickening, as assessed at the biopsy visit
4.18 years of age or over
5.Patients must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
6.Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures

* The ACR/EULAR classification for a diagnosis of RA could have been at any time in the patient’s disease history; the score does not need to be 6 or more at screening.
**According to the UK National Institute for Health and Care Excellence (NICE) guidelines, the TNF-a inhibitors are recommended as options for the treatment of adults who have both of the following characteristics:
1)Disease is severe, that is, a disease activity score (DAS28) greater than 5.1
2)Disease has not responded to intensive therapy with a combination of conventional disease modifying antirheumatic drugs (DMARDs).
Current NICE guidelines available at the following link: http://www.nice.org.uk/guidance/ta375.
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

Patients will be excluded if they have any contraindication to Etanercept, Rituximab or Tocilizumab therapy:

1.Women who are pregnant or breast-feeding
2.Women of child-bearing potential or males whose partners are women of child-bearing potential, unwilling to use an effective method of contraception (recommend double contraception) throughout the trial and beyond the end of trial treatment for the duration as defined in the relevant SmPC; 12 months for Rituximab, at least 3 weeks for Etanercept, and at least 3 months for Tocilizumab.
3.History of or current primary inflammatory joint disease or primary rheumatological autoimmune disease other than RA (if secondary to RA, then the patient is still eligible).
4.Prior exposure to Rituximab, any anti-TNF, Tocilizumab, or any other biologic for treatment of RA
5.Treatment with any investigational agent = 4 weeks prior to baseline or < 5 half-lives of the investigational drug (whichever is the longer)
6.Intra-articular or parenteral corticosteroids = 4 weeks prior to screening visit.
7.Oral prednisolone more than 10mg/d or equivalent = 4 weeks prior to baseline synovial biopsy.
8.Active infection
9.Known HIV, active Hepatitis B/C infection. Hepatitis B screening test must be performed at or in the preceding 3 months of screening visit.
10.Septic arthritis of a native joint within the last 12 months
11.Septic arthritis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ
12.Latent TB infection unless they have completed adequate antibiotic prophylaxis
13.Malignancy (other than basal cell carcinoma) within the last 10 years
14.New York Heart Association (NYHA) grade III or IV congestive heart failure
15.Demyelinating disease
16.Known allergy to latex, Rituximab, Tocilizumab or Etanercept
17.Any other contra-indication to the study medications as detailed in the applicable SmPC including low IgG levels, at physician’s discretion
18.Receipt of live vaccine <4 weeks prior to first IMP infusion or dose
19.Major surgery in 3 months prior to first IMP infusion or dose
20.Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening).
21.Known recent substance abuse (drug or alcohol).
22.Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period
23.Patients unable to tolerate synovial biopsy or in whom this is contraindicated including patients on anti-coagulants. Oral anti-platelet agents are permitted.
24.Patients currently recruited to other clinical trials.
25.Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Study & Design

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