Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation (RAFTING)

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

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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Tocilizumab; Drug: Etanercept; Drug: Infliximab; Drug: Adalimumab; Drug: Golimumab; Drug: Certolizumab Pegol

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 Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy
    • Azienda Consorziale Ospedaliera Policlinico
  • Bergamo, Italy
    • Azienda Socio Sanitaria Territoriale - Papa Giovanni XXIII
  • Bologna, Italy
    • Policlinico Sant'Orsola Malpighi
  • Bolzano, Italy
    • Ospedale Centrale di Bolzano
  • Catania, Italy
    • Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele
  • Cona, Italy
    • Azienda Ospedaliera-Universitaria S.Anna c/o Nuovo Arcispedale S. Anna
  • Cuneo, Italy
    • Azienda Ospedaliera Santa Croce e Carle
  • Firenze, Italy
    • Universita Di Firenze
  • Messina, Italy
    • Azienda Ospedaliera Universitaria Di Messina
  • Milano, Italy
    • Istituto Ortopedico Gaetano Pini
  • Modena, Italy
    • Azienda Ospedaliera Universitaria Policlinico Di Modena
  • Monserrato, Italy
    • Policlinico Universitario Monserrato
  • Napoli, Italy
    • Asl Napoli 1 Centro
  • Parma, Italy
    • Ospedale Maggiore di Parma
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
  • Roma, Italy
    • Azienda Ospedaliera San Camillo Forlanini
  • Rozzano, Italy
    • Istituto Clinico Humanitas
  • Sassari, Italy
    • Ospedale SS Annunziata
  • Torino, Italy
    • Azienda Ospedaliera Universitaria Città della Salute e della Scienza
  • Trento, Italy
    • Ospedale Santa Chiara
  • Udine, Italy
    • Azienda Sanitaria Universitaria Integrata di Udine Sanata Maria della Misericordia
  • Verona, Italy
    • Azienda Ospedaliera Universitaria Integrata Verona - Policlinico GB Rossi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with good EULAR	the proportion of patients with good EULAR response	24 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Mauro Galeazzi, Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Tocilizumab; anti-TNF treatment
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Tumor Necrosis Factor Inhibitors; Etanercept; Adalimumab; Infliximab; Golimumab; Certolizumab Pegol
• Other Study ID Numbers: IRFMN-RA-6453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No