Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation

NCT03100253 | Terminated Phase 4 DMC

• 1 other identifier: IRFMN-RA-6453
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 22

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Tocilizumab; anti-TNF treatment

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with good EULAR

  the proportion of patients with good EULAR response

  24 weeks

Secondary Outcomes (12)

• Proportion of patients with a good/moderate EULAR

  12 weeks

• Proportion of patients with a good/moderate EULAR

  24 weeks

• Proportion of patients with ACR20/50/70 response

  12 weeks

• Proportion of patients with ACR20/50/70 response

  24 weeks

• Proportion of patients with a remission according to DAS28/SDAI/CDAI

  24 weeks

Study Arms (2)

"Switching" strategy

EXPERIMENTAL

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

Drug: Tocilizumab

"Cycling" strategy

ACTIVE COMPARATOR

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.

Drug: Etanercept; Drug: Infliximab; Drug: Adalimumab; Drug: Golimumab; Drug: Certolizumab Pegol

Interventions

Tocilizumab DRUG

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

"Switching" strategy

Etanercept DRUG

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

"Cycling" strategy

Infliximab DRUG

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

"Cycling" strategy

Adalimumab DRUG

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

"Cycling" strategy

Golimumab DRUG

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

"Cycling" strategy

Certolizumab Pegol DRUG

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

"Cycling" strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (22)

Azienda Consorziale Ospedaliera Policlinico

Bari, Italy

Location

Azienda Socio Sanitaria Territoriale - Papa Giovanni XXIII

Bergamo, Italy

Location

Policlinico Sant'Orsola Malpighi

Bologna, Italy

Location

Ospedale Centrale di Bolzano

Bolzano, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele

Catania, Italy

Location

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

Cona, Italy

Location

Azienda Ospedaliera Santa Croce e Carle

Cuneo, Italy

Location

Università di Firenze

Florence, Italy

Location

Azienda Ospedaliera Universitaria Di Messina

Messina, Italy

Location

Istituto Ortopedico Gaetano Pini

Milan, Italy

Location

Azienda Ospedaliera Universitaria Policlinico di Modena

Modena, Italy

Location

Policlinico Universitario Monserrato

Monserrato, Italy

Location

Asl Napoli 1 centro

Napoli, Italy

Location

Ospedale Maggiore di Parma

Parma, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Roma, Italy

Location

Istituto Clinico Humanitas

Rozzano, Italy

Location

Ospedale SS Annunziata

Sassari, Italy

Location

Azienda Ospedaliera Universitaria Città della Salute e della Scienza

Torino, Italy

Location

Ospedale Santa Chiara

Trento, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine Sanata Maria della Misericordia

Udine, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona - Policlinico GB Rossi

Verona, Italy

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Etanercept; Infliximab; Adalimumab; golimumab; Certolizumab Pegol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal; Antibodies; Antibodies, Monoclonal, Humanized; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments

Study Officials

• Mauro Galeazzi

  Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: April 4, 2017
• Study Start: March 1, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 31, 2021
• Last Updated: September 19, 2022

Record last verified: 2022-09

Locations

IT (22)