Clinical trial NCT03100253: Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Tocilizumab
anti-TNF treatment
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2017-04-04
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of patients with good EULAR
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of patients with a good/moderate EULAR
timeFrame: 12 weeks
measure: Proportion of patients with a good/moderate EULAR
timeFrame: 24 weeks
measure: Proportion of patients with ACR20/50/70 response
timeFrame: 12 weeks
measure: Proportion of patients with ACR20/50/70 response
timeFrame: 24 weeks
measure: Proportion of patients with a remission according to DAS28/SDAI/CDAI
timeFrame: 24 weeks
measure: Proportion of patients with a remission according to DAS28/SDAI/CDAI
timeFrame: 48 weeks
measure: Proportion of patients with a remission according to DAS28/SDAI/CDAI
timeFrame: 96 weeks
measure: Van Der Heijde Modified Total Sharp Score [X-ray score]
timeFrame: 48 weeks
measure: Van Der Heijde Modified Total Sharp Score [X-ray score]
timeFrame: 96 weeks
measure: Health Assessment Questionnaire (HAQ) score
timeFrame: 24 weeks
measure: Health Assessment Questionnaire (HAQ) score
timeFrame: 48 weeks
measure: Health Assessment Questionnaire (HAQ) score
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Azienda Consorziale Ospedaliera Policlinico
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale - Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Bolzano
country: Italy
facility: Ospedale Centrale di Bolzano
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele
city: Cona
country: Italy
facility: Azienda Ospedaliera-Universitaria S.Anna c/o Nuovo Arcispedale S. Anna
city: Cuneo
country: Italy
facility: Azienda Ospedaliera Santa Croce e Carle
city: Firenze
country: Italy
facility: Università di Firenze
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Di Messina
city: Milano
country: Italy
facility: Istituto Ortopedico Gaetano Pini
city: Modena
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico di Modena
city: Monserrato
country: Italy
facility: Policlinico Universitario Monserrato
city: Napoli
country: Italy
facility: Asl Napoli 1 centro
city: Parma
country: Italy
facility: Ospedale Maggiore di Parma
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Sassari
country: Italy
facility: Ospedale SS Annunziata
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Città della Salute e della Scienza
city: Trento
country: Italy
facility: Ospedale Santa Chiara
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine Sanata Maria della Misericordia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Policlinico GB Rossi
Study officials:
affiliation: Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
name: Mauro Galeazzi
role: PRINCIPAL_INVESTIGATOR
References: