Clinical study aimed to compare tocilizumab to anti-TNF treatment and to discover biomarkers for treatment selection in rheumatoid arthritis patients with inadequate response to a first anti-TNF

Phase 1

• Conditions: RHEUMATOID ARTHRITIS; MedDRA version: 20.0Level: LLTClassification code 10037738Term: R arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; MedDRA version: 23.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; MedDRA version: 20.0Level: LLTClassification code 10039014Term: Rh arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; MedDRA version: 23.1Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2016-001987-12-IT
• Lead Sponsor: SOCIETA' ITALIANA DI REUMATOLOGIA - SIR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-05
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 208

Inclusion Criteria

-Age =18 years at the time of signing the informed consent form and either male or female
-Diagnosis of RA according to the 1987 ACR classification criteria OR 2010 ACR/EULAR classification criteria at least 6 months prior to screening
-Patients with persistent RA disease activity whilst being treated with an initial TNFi agent on a background MTX up to 20-25 mg/week for at least 12 weeks defined according to SIR and EULAR guidelines as:
A)Primary non-response: failing to improve DAS28 by = 1.2 or failing to achieve DAS28 = 3.2 within the first three to six months of starting the initial TNFi;
B)Secondary non-response: determined by physician decision with evidence of flare and deterioration in DAS28 of = 1.2
C)Drug withdrawal for adverse events (not contraindicating a second course of TNFi (not class-adverse events))
-Methotrexate (MTX) dose stable for 28 days prior to screening
-Patients on NSAIDs and / or corticosteroids must remain on an unchanged regimen for at least 28 days prior to study drug administration
-The patient must be able to comply with the study visit schedule and other protocol requirements
-The patient understands the purpose of the study and is able and willing to sign the informed consent form, according to ICH/GCP
-Signed written informed consent for biological analysis
-Female patients with reproductive potential must have a negative pregnancy test within 7 days prior to start of trial. Women of childbearing potential and male patients must be willing to adopt practice acceptable methods of highly effective contraception measures during treatment and for 6 months (female patients) and 3 months (male patients) after discontinuation of treatment.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

-Patients who have previously received more than 1 TNFi drug OR any other biological therapy
-Patients with inflammatory joint disease of different origin or any arthritis with onset prior to 16 years of age
-Patients taking any disease-modifying antirheumatic drug (DMARDs) (e.g. all except methotrexate). Discontinuation must occur at least 28 days prior to study treatment start
-History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug
-Known hypersensitivity to any active substance or excipients of study drug
-Pregnancy or breast feeding.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of switching to a different molecular target (from TNF to IL6) versus cycling to a second TNF inhibitor in patients with active RA, who have not adequately responded to a previous treatment with a first anti-TNF. ;Secondary Objective: To compare the effect of switching versus cycling on clinical remission, radiological progression, functional disability, pain intensity and health related quality of life;<br>To undertake an evaluation of the cost-effectiveness of switching patients to an alternative-mechanism (anti-IL6) versus cycling to another anti-TNF; <br>To assess the safety profile for the treatment in study, evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, and by the incidence of serious adverse events (SAEs), expected and unexpected.;Primary end point(s): the proportion of patients with good EULAR response at 24 weeks.;Timepoint(s) of evaluation of this end point: 24 weeks