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

September 16, 2022 updated by: Mario Negri Institute for Pharmacological Research

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
208

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
  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
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of patients with good EULAR
Time Frame: 24 weeks
the proportion of patients with good EULAR response
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of patients with a good/moderate EULAR
Time Frame: 12 weeks
Proportion of patients with a good/moderate EULAR response
12 weeks
Proportion of patients with a good/moderate EULAR
Time Frame: 24 weeks
Proportion of patients with a good/moderate EULAR response
24 weeks
Proportion of patients with ACR20/50/70 response
Time Frame: 12 weeks
Proportion of patients with ACR20/50/70 response
12 weeks
Proportion of patients with ACR20/50/70 response
Time Frame: 24 weeks
Proportion of patients with ACR20/50/70 response
24 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Time Frame: 24 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
24 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Time Frame: 48 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
48 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Time Frame: 96 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
96 weeks
Van Der Heijde Modified Total Sharp Score [X-ray score]
Time Frame: 48 weeks
Van Der Heijde Modified Total Sharp Score [X-ray score]
48 weeks
Van Der Heijde Modified Total Sharp Score [X-ray score]
Time Frame: 96 weeks
Van Der Heijde Modified Total Sharp Score [X-ray score]
96 weeks
Health Assessment Questionnaire (HAQ) score
Time Frame: 24 weeks
Health Assessment Questionnaire (HAQ) score
24 weeks
Health Assessment Questionnaire (HAQ) score
Time Frame: 48 weeks
Health Assessment Questionnaire (HAQ) score
48 weeks
Health Assessment Questionnaire (HAQ) score
Time Frame: 96 weeks
Health Assessment Questionnaire (HAQ) score
96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Mario Negri Institute for Pharmacological Research

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mauro Galeazzi, Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 4, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Drug Interventions

Conditions

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Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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