RAFTING: Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation

Sponsor

Mario Negri Institute for Pharmacological Research (Other)

Overall Status

Recruiting

CT.gov ID

NCT03100253

Collaborator

(none)

208

Enrollment

Locations

Arms

Anticipated Duration (Months)

9.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Tocilizumab Drug: Etanercept Drug: Infliximab Drug: Adalimumab Drug: Golimumab Drug: Certolizumab Pegol	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

208 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 1, 2018

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: "Switching" strategy Tocilizumab [RoActemra®] [ATC: L04AC07] 8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days	Drug: Tocilizumab 8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days
Active Comparator: "Cycling" strategy Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab OR Infliximab, adalimumab, golimumab or certolizumab if initial failure to the receptor fusion protein, etanercept.	Drug: Etanercept a. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab Drug: Infliximab infliximab if initial failure to the receptor fusion protein, etanercept. Drug: Adalimumab adalimumab if initial failure to the receptor fusion protein, etanercept. Drug: Golimumab golimumab if initial failure to the receptor fusion protein, etanercept. Drug: Certolizumab Pegol Certolizumab Pegol if initial failure to the receptor fusion protein, etanercept.

Arm

Intervention/Treatment

Experimental: "Switching" strategy

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

Drug: Tocilizumab

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

Active Comparator: "Cycling" strategy

Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab OR Infliximab, adalimumab, golimumab or certolizumab if initial failure to the receptor fusion protein, etanercept.

Drug: Etanercept

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

Drug: Infliximab

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

Drug: Adalimumab

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

Drug: Golimumab

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

Drug: Certolizumab Pegol

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

Outcome Measures

Primary Outcome Measures

Proportion of patients with good EULAR [24 weeks]
the proportion of patients with good EULAR response

Secondary Outcome Measures

Proportion of patients with a good/moderate EULAR [12 weeks]
Proportion of patients with a good/moderate EULAR response
Proportion of patients with a good/moderate EULAR [24 weeks]
Proportion of patients with a good/moderate EULAR response
Proportion of patients with ACR20/50/70 response [12 weeks]
Proportion of patients with ACR20/50/70 response
Proportion of patients with ACR20/50/70 response [24 weeks]
Proportion of patients with ACR20/50/70 response
Proportion of patients with a remission according to DAS28/SDAI/CDAI [24 weeks]
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Proportion of patients with a remission according to DAS28/SDAI/CDAI [48 weeks]
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Proportion of patients with a remission according to DAS28/SDAI/CDAI [96 weeks]
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Van Der Heijde Modified Total Sharp Score [X-ray score] [48 weeks]
Van Der Heijde Modified Total Sharp Score [X-ray score]
Van Der Heijde Modified Total Sharp Score [X-ray score] [96 weeks]
Van Der Heijde Modified Total Sharp Score [X-ray score]
Health Assessment Questionnaire (HAQ) score [24 weeks]
Health Assessment Questionnaire (HAQ) score
Health Assessment Questionnaire (HAQ) score [48 weeks]
Health Assessment Questionnaire (HAQ) score
Health Assessment Questionnaire (HAQ) score [96 weeks]
Health Assessment Questionnaire (HAQ) score

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Azienda Consorziale Ospedaliera Policlinico	Bari	Italy
2	Azienda Socio Sanitaria Territoriale - Papa Giovanni XXIII	Bergamo	Italy
3	Policlinico Sant'Orsola Malpighi	Bologna	Italy
4	Ospedale Centrale di Bolzano	Bolzano	Italy
5	Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele	Catania	Italy
6	Azienda Ospedaliera-Universitaria S.Anna c/o Nuovo Arcispedale S. Anna	Cona	Italy
7	Azienda Ospedaliera Santa Croce e Carle	Cuneo	Italy
8	Università di Firenze	Firenze	Italy
9	Azienda Ospedaliera Universitaria Di Messina	Messina	Italy
10	Istituto Ortopedico Gaetano Pini	Milano	Italy
11	Azienda Ospedaliera Universitaria Policlinico di Modena	Modena	Italy
12	Policlinico Universitario Monserrato	Monserrato	Italy
13	Asl Napoli 1 centro	Napoli	Italy
14	Ospedale Maggiore di Parma	Parma	Italy
15	Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
16	Azienda Ospedaliera San Camillo Forlanini	Roma	Italy
17	Istituto Clinico Humanitas	Rozzano	Italy
18	Ospedale SS Annunziata	Sassari	Italy
19	Azienda Ospedaliera Universitaria Città della Salute e della Scienza	Torino	Italy
20	Ospedale Santa Chiara	Trento	Italy
21	Azienda Sanitaria Universitaria Integrata di Udine Sanata Maria della Misericordia	Udine	Italy
22	Azienda Ospedaliera Universitaria Integrata Verona - Policlinico GB Rossi	Verona	Italy