Rheumatoid ArthritisPhase 4RAFTINGNCT03100253
Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation
A Phase 4 study testing Tocilizumab, Etanercept and Infliximab in people with Rheumatoid Arthritis, run by Mario Negri Institute for Pharmacological Research at 22 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Tocilizumab, Etanercept and Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 208 participants
- Where
- 22 sitesItaly
- Study dates
- 1 Mar 2018to 31 Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
Italy22 sites
Azienda Consorziale Ospedaliera Policlinico
Bari
Azienda Socio Sanitaria Territoriale - Papa Giovanni XXIII
Bergamo
Policlinico Sant'Orsola Malpighi
Bologna
Ospedale Centrale di Bolzano
Bolzano
Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele
Catania
Azienda Ospedaliera-Universitaria S.Anna c/o Nuovo Arcispedale S. Anna
Cona
Azienda Ospedaliera Santa Croce e Carle
Cuneo
Università di Firenze
Florence
Azienda Ospedaliera Universitaria Di Messina
Messina
Istituto Ortopedico Gaetano Pini
Milan
Azienda Ospedaliera Universitaria Policlinico di Modena
Modena
Policlinico Universitario Monserrato
Monserrato
Asl Napoli 1 centro
Naples
Ospedale Maggiore di Parma
Parma
Fondazione IRCCS Policlinico San Matteo
Pavia
Azienda Ospedaliera San Camillo Forlanini
Roma
Istituto Clinico Humanitas
Rozzano
Ospedale SS Annunziata
Sassari
Azienda Ospedaliera Universitaria Città della Salute e della Scienza
Torino
Ospedale Santa Chiara
Trento
Azienda Sanitaria Universitaria Integrata di Udine Sanata Maria della Misericordia
Udine
Azienda Ospedaliera Universitaria Integrata Verona - Policlinico GB Rossi
Verona
About this study
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
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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Tocilizumab, Etanercept, Infliximab, Adalimumab, Golimumab
- Keywords
- Rheumatoid Arthritis, Tocilizumab, anti-TNF treatment
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days
EtanerceptDrug
- Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab
InfliximabDrug
infliximab if initial failure to the receptor fusion protein, etanercept.
AdalimumabDrug
adalimumab if initial failure to the receptor fusion protein, etanercept.
GolimumabDrug
golimumab if initial failure to the receptor fusion protein, etanercept.
Certolizumab PegolDrug
Certolizumab Pegol if initial failure to the receptor fusion protein, etanercept.
| Study group | Role | What they receive |
|---|---|---|
| "Switching" strategy | Experimental | Tocilizumab [RoActemra®] [ATC: L04AC07] 8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days Receives: Drug: Tocilizumab |
| "Cycling" strategy | Active comparator | 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. Receives: Drug: Etanercept; Drug: Infliximab; Drug: Adalimumab; Drug: Golimumab; Drug: Certolizumab Pegol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with good EULAR
the proportion of patients with good EULAR response
Measured: 24 weeks
Secondary outcomes (12)
Proportion of patients with a good/moderate EULAR
Proportion of patients with a good/moderate EULAR response
Measured: 12 weeks
Proportion of patients with a good/moderate EULAR
Proportion of patients with a good/moderate EULAR response
Measured: 24 weeks
Proportion of patients with ACR20/50/70 response
Proportion of patients with ACR20/50/70 response
Measured: 12 weeks
Proportion of patients with ACR20/50/70 response
Proportion of patients with ACR20/50/70 response
Measured: 24 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Measured: 24 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Measured: 48 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Measured: 96 weeks
Van Der Heijde Modified Total Sharp Score [X-ray score]
Van Der Heijde Modified Total Sharp Score [X-ray score]
Measured: 48 weeks
Van Der Heijde Modified Total Sharp Score [X-ray score]
Van Der Heijde Modified Total Sharp Score [X-ray score]
Measured: 96 weeks
Health Assessment Questionnaire (HAQ) score
Health Assessment Questionnaire (HAQ) score
Measured: 24 weeks
Health Assessment Questionnaire (HAQ) score
Health Assessment Questionnaire (HAQ) score
Measured: 48 weeks
Health Assessment Questionnaire (HAQ) score
Health Assessment Questionnaire (HAQ) score
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start1 Mar 2018
- Primary completion1 Dec 2021
- Study completion31 Dec 2021
Why it stopped: Slow recrutiment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mauro Galeazzi, Principal investigator, Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03100253
- Sponsor's protocol ID
- IRFMN-RA-6453
- Acronym
- RAFTING
- Status last verified
- Sep 2022
- First submitted
- 17 Mar 2017
- Last updated
- 19 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03100253
- Acronym / sponsor ID
- RAFTING / IRFMN-RA-6453
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Tocilizumab, anti-TNF treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recrutiment
- Enrolment
- 208 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| "Switching" strategy | Experimental | Drug: TocilizumabTocilizumab [RoActemra®] [ATC: L04AC07] 8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days |
| "Cycling" strategy | Active comparator | Drug: Etanercept, Drug: Infliximab, Drug: Adalimumab, Drug: Golimumab, Drug: Certolizumab Pegol1. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tocilizumab8 mg/kg i.v. every 4 weeks OR 162 mg s.c every seven days | Drug | "Switching" strategy |
| Etanercepta. Etanercept if initial failure to monoclonal antibodies: infliximab, adalimumab, golimumab or certolizumab | Drug | "Cycling" strategy |
| Infliximabinfliximab if initial failure to the receptor fusion protein, etanercept. | Drug | "Cycling" strategy |
| Adalimumabadalimumab if initial failure to the receptor fusion protein, etanercept. | Drug | "Cycling" strategy |
| Golimumabgolimumab if initial failure to the receptor fusion protein, etanercept. | Drug | "Cycling" strategy |
| Certolizumab PegolCertolizumab Pegol if initial failure to the receptor fusion protein, etanercept. | Drug | "Cycling" strategy |
Primary outcome
Proportion of patients with good EULAR
Time frame: 24 weeks
the proportion of patients with good EULAR response
12 secondary outcomes
Proportion of patients with a good/moderate EULAR
Time frame: 12 weeks
Proportion of patients with a good/moderate EULAR
Time frame: 24 weeks
Proportion of patients with ACR20/50/70 response
Time frame: 12 weeks
Proportion of patients with ACR20/50/70 response
Time frame: 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
Time frame: 48 weeks
Proportion of patients with a remission according to DAS28/SDAI/CDAI
Time frame: 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]
Time frame: 96 weeks
Health Assessment Questionnaire (HAQ) score
Time frame: 24 weeks
Health Assessment Questionnaire (HAQ) score
Time frame: 48 weeks
Health Assessment Questionnaire (HAQ) score
Time frame: 96 weeks
Results and safety
The study was stopped early (reason given: Slow recrutiment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mauro Galeazzi principal investigator
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tocilizumab, Etanercept and Infliximab in people with Rheumatoid Arthritis, run by Mario Negri Institute for Pharmacological Research at 22 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recrutiment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with good EULAR (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2022.