Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation

Rheumatoid Arthritis Clinical Trial

— RAFTING  

Official title:

Open-label, Randomized Controlled Trial Comparing Tocilizumab to Anti-TNF Treatment and Discovery of Biomarkers for Treatment Selection in Rheumatoid Arthritis Patients With Inadequate Response to a First Anti-TNF

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03100253
• Other study ID #: IRFMN-RA-6453
• Status: Terminated
• Phase: Phase 4
• Start date: March 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2022
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 208
• Est. completion date: December 31, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tocilizumab
8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days
• Etanercept
a. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab
• Infliximab
infliximab if initial failure to the receptor fusion protein, etanercept.
• Adalimumab
adalimumab if initial failure to the receptor fusion protein, etanercept.
• Golimumab
golimumab if initial failure to the receptor fusion protein, etanercept.
• Certolizumab Pegol
Certolizumab Pegol if initial failure to the receptor fusion protein, etanercept.

Locations

Country	Name	City	State
Italy	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	Firenze
Italy	Azienda Ospedaliera Universitaria Di Messina	Messina
Italy	Istituto Ortopedico Gaetano Pini	Milano
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

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with good EULAR	the proportion of patients with good EULAR response	24 weeks
Secondary	Proportion of patients with a good/moderate EULAR	Proportion of patients with a good/moderate EULAR response	12 weeks
Secondary	Proportion of patients with a good/moderate EULAR	Proportion of patients with a good/moderate EULAR response	24 weeks
Secondary	Proportion of patients with ACR20/50/70 response	Proportion of patients with ACR20/50/70 response	12 weeks
Secondary	Proportion of patients with ACR20/50/70 response	Proportion of patients with ACR20/50/70 response	24 weeks
Secondary	Proportion of patients with a remission according to DAS28/SDAI/CDAI	Proportion of patients with a remission according to DAS28/SDAI/CDAI	24 weeks
Secondary	Proportion of patients with a remission according to DAS28/SDAI/CDAI	Proportion of patients with a remission according to DAS28/SDAI/CDAI	48 weeks
Secondary	Proportion of patients with a remission according to DAS28/SDAI/CDAI	Proportion of patients with a remission according to DAS28/SDAI/CDAI	96 weeks
Secondary	Van Der Heijde Modified Total Sharp Score [X-ray score]	Van Der Heijde Modified Total Sharp Score [X-ray score]	48 weeks
Secondary	Van Der Heijde Modified Total Sharp Score [X-ray score]	Van Der Heijde Modified Total Sharp Score [X-ray score]	96 weeks
Secondary	Health Assessment Questionnaire (HAQ) score	Health Assessment Questionnaire (HAQ) score	24 weeks
Secondary	Health Assessment Questionnaire (HAQ) score	Health Assessment Questionnaire (HAQ) score	48 weeks
Secondary	Health Assessment Questionnaire (HAQ) score	Health Assessment Questionnaire (HAQ) score	96 weeks