Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation

NCT ID: NCT03100253

Last Updated: 2022-09-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2021-12-31

Brief Summary

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.

Detailed Description

New drugs for the treatment of rheumatoid arthritis (RA) with action on specific molecular target (e.g. anti-TNF) have improved the prognosis of patients with an inadequate response to conventional therapy such as methotrexate (MTX).

However, approximately 50% of patients treated with first-line anti-TNF discontinue treatment after two years due to ineffectiveness or adverse events. The second line treatment involves the use of another anti-TNF drug or switching to a different molecular target (anti-IL6, -CD20 or CTLA-4-Ig) in combination with MTX.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

"Switching" strategy

Tocilizumab \[RoActemra®\] \[ATC: L04AC07\] 8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days

"Cycling" strategy

1. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab OR

2. Infliximab, adalimumab, golimumab or certolizumab if initial failure to the receptor fusion protein, etanercept.

Group Type: ACTIVE_COMPARATOR

Etanercept

Intervention Type: DRUG

a. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab

Infliximab

Intervention Type: DRUG

infliximab if initial failure to the receptor fusion protein, etanercept.

Adalimumab

Intervention Type: DRUG

adalimumab if initial failure to the receptor fusion protein, etanercept.

Golimumab

Intervention Type: DRUG

golimumab if initial failure to the receptor fusion protein, etanercept.

Certolizumab Pegol

Intervention Type: DRUG

Certolizumab Pegol if initial failure to the receptor fusion protein, etanercept.

Interventions

Tocilizumab

8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days

Intervention Type: DRUG

Etanercept

a. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab

Intervention Type: DRUG

Infliximab

infliximab if initial failure to the receptor fusion protein, etanercept.

Intervention Type: DRUG

Adalimumab

adalimumab if initial failure to the receptor fusion protein, etanercept.

Intervention Type: DRUG

Golimumab

golimumab if initial failure to the receptor fusion protein, etanercept.

Intervention Type: DRUG

Certolizumab Pegol

Certolizumab Pegol if initial failure to the receptor fusion protein, etanercept.

Intervention Type: DRUG

Eligibility Criteria

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: 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; secondary non-response: determined by physician decision with evidence of flare and deterioration in DAS28 of ≥ 1.2.
• 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 serum pregnancy test within 7 days prior to start of trial. Women of childbearing potential and male patients must be willing to practice acceptable methods of contraception during treatment and for 6 months (female patients) and 3 months (male patients) after discontinuation of treatment.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mauro Galeazzi

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

Locations

Azienda Consorziale Ospedaliera Policlinico

Bari, , Italy

Azienda Socio Sanitaria Territoriale - Papa Giovanni XXIII

Bergamo, , Italy

Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Ospedale Centrale di Bolzano

Bolzano, , Italy

Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele

Catania, , Italy

Azienda Ospedaliera-Universitaria S.Anna c/o Nuovo Arcispedale S. Anna

Cona, , Italy

Azienda Ospedaliera Santa Croce e Carle

Cuneo, , Italy

Università di Firenze

Florence, , Italy

Azienda Ospedaliera Universitaria Di Messina

Messina, , Italy

Istituto Ortopedico Gaetano Pini

Milan, , Italy

Azienda Ospedaliera Universitaria Policlinico di Modena

Modena, , Italy

Policlinico Universitario Monserrato

Monserrato, , Italy

Asl Napoli 1 centro

Napoli, , Italy

Ospedale Maggiore di Parma

Parma, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Azienda Ospedaliera San Camillo Forlanini

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Ospedale SS Annunziata

Sassari, , Italy

Azienda Ospedaliera Universitaria Città della Salute e della Scienza

Torino, , Italy

Ospedale Santa Chiara

Trento, , Italy

Azienda Sanitaria Universitaria Integrata di Udine Sanata Maria della Misericordia

Udine, , Italy

Azienda Ospedaliera Universitaria Integrata Verona - Policlinico GB Rossi

Verona, , Italy

Countries

Italy

Other Identifiers

IRFMN-RA-6453

Identifier Type: -

Identifier Source: org_study_id