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

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ClinicalTrials.gov Identifier: NCT03100253
Recruitment Status : Recruiting
First Posted : April 4, 2017
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 1, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

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
  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.




Primary Outcome Measures :
  1. Proportion of patients with good EULAR [ Time Frame: 24 weeks ]
    the proportion of patients with good EULAR response


Secondary Outcome Measures :
  1. Proportion of patients with a good/moderate EULAR [ Time Frame: 12 weeks ]
    Proportion of patients with a good/moderate EULAR response

  2. Proportion of patients with a good/moderate EULAR [ Time Frame: 24 weeks ]
    Proportion of patients with a good/moderate EULAR response

  3. Proportion of patients with ACR20/50/70 response [ Time Frame: 12 weeks ]
    Proportion of patients with ACR20/50/70 response

  4. Proportion of patients with ACR20/50/70 response [ Time Frame: 24 weeks ]
    Proportion of patients with ACR20/50/70 response

  5. 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

  6. 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

  7. 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

  8. Van Der Heijde Modified Total Sharp Score [X-ray score] [ Time Frame: 48 weeks ]
    Van Der Heijde Modified Total Sharp Score [X-ray score]

  9. Van Der Heijde Modified Total Sharp Score [X-ray score] [ Time Frame: 96 weeks ]
    Van Der Heijde Modified Total Sharp Score [X-ray score]

  10. Health Assessment Questionnaire (HAQ) score [ Time Frame: 24 weeks ]
    Health Assessment Questionnaire (HAQ) score

  11. Health Assessment Questionnaire (HAQ) score [ Time Frame: 48 weeks ]
    Health Assessment Questionnaire (HAQ) score

  12. Health Assessment Questionnaire (HAQ) score [ Time Frame: 96 weeks ]
    Health Assessment Questionnaire (HAQ) score



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03100253


Contacts
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Contact: Carlo Scirè +390239014519 c.scire@reumatologia.it
Contact: Simona Stupia +390239014519 simona.stupia@marionegri.it

Locations
Show Show 22 study locations
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Investigators
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Principal Investigator: Mauro Galeazzi Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte
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Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT03100253    
Other Study ID Numbers: IRFMN-RA-6453
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mario Negri Institute for Pharmacological Research:
Rheumatoid Arthritis
Tocilizumab
anti-TNF treatment
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Etanercept
Infliximab
Certolizumab Pegol
Anti-Inflammatory Agents
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Dermatologic Agents