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)

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 19.0Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2012-002535-28-NL
• 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: 2016-09-01
• Study Completion: 2019-07-11
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 164

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 to the guideline 'Doelmatig gebruik van biologicals bij reumatoide artritis, axiale spondyloartritis en artritis psoriatica' of the Dutch Society of Rheumatology (NVR).
3.Patients should be receiving a stable dose Methotrexate for at least 4 weeks prior to biopsy visit.
4.2010 ACR / EULAR Rheumatoid Arthritis classification criteria for a diagnosis of Rheumatoid Arthritis.
5.Over 18 years of age
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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

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 12 months after stopping study treatment.
3.History of or current primary inflammatory joint disease or primary autoimmune disease other than RA.
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, whichever is the longer).
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 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 (e.g. patients on anti-coagulants).
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 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