A Randomised, open labelled study in anti-TNFa inadequate responders to investigate the mechanisms for Response - Resistance to Rituximab versus Tocilizumab in RA (R4-RA) - R4-RA

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 20.0 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2012-002535-28-BE
• Lead Sponsor: Joint Research & Development Office (Barts and The London School of Medicine & Dentistry)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-28
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 160

Inclusion Criteria

Patients will be recruited with active RA:
1. Patients who have failed anti-TNF therapy (inadequate responders – ir). Note: this includes patients that have failed anti-TNF therapy because of reactions.
2. Who are eligible for Rituximab therapy according NICE guidlines*
3. Patients should be receiving a stable dose Methotrexate for at least 4 weeks prior to the biopsy visit.
4. 2010 ACR / EULAR Rheumatoid Arthritis classification criteria for a diagnosis of Rheumatoid Arthritis.
5. 18 years of age or over
6. Patient must be capable of giving informed consent
7. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures

*Reference to NICE guidelines: 1.1 Rituximuab in combination with methotrexate is recommended as an option for the treatment of adults with severe active rheumatoid arthritis who have had an inadequate response to or intolerance of other disease-modifying anti-rheumatic drugs (DMARDS), including treatment with at least one tumour necrosis factor alpha (TNF alpha) inhibitor therapy.
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 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

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 effective contraception during the study and for at least 6 months after stopping study treatment.
3.History of or current primary rheumatological inflammatory joint disease or primary autoimmune disease other than RA (if secondary to RA, then the patient is still eligible)
4. Prior exposure to Rituximab or Tocilizumab for the treatment of RA
5.Treatment with any investigational agent = 4 weeks prior to baseline or < 5 half lives of the investigational drug
6.Intra articular or parenteral corticosteroids = 4 weeks prior to biopsy visit (Visit 2)
7. Oral Prednisolone more than 10mg per day or equivalent = 4 weeks prior to biopsy visit (Visit 2)
8.Active infection
9.Septic arthritis within a native joint within the last 12 months
10.Sepsis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ
11.Known HIV or active hepatitis B/C infection. Hepatitis B screening test must be performed at or in the preceding 3 months of screening visit.
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 3 or 4 congestive cardiac failure
15.Demyelinating disease
16.Latex allergy or allergy to any excipients of Rituximab or Tocilizumab
17.Any other contra-indication to the study medications as detailed in their summaries of product characteristics (SmPC) including low IgG levels at clinician's discretion
18.Receipt of live vaccine <4 weeks prior to first infusion
19. Major surgery in 3 months prior to first infusion
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 trial(s) involving an investigational medicinal product (except any observational follow-up periods not involving an IMP).
25. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgement of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgement 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