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Trial record 49 of 70 for:    response | "Connective Tissue Disease" | "Abatacept"

Abatacept vs Tocilizumab for the Treatment of RA in TNF Alpha Inhibitor Inadequate Responders (SUNSTAR)

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ClinicalTrials.gov Identifier: NCT03227419
Recruitment Status : Recruiting
First Posted : July 24, 2017
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Lille Catholic University

Brief Summary:

Rheumatoid arthritis (RA) is the most common inflammatory rheumatoid disease in France, affecting 0.3% of the general population. Without effective treatment, the persistent inflammation causes invalidating pain and joint destruction, leading to major functional disability.

Biological agents have been proposed for patients with RA who have the most severe form of the disease and that are inadequate responder patients to conventional synthetic Disease-modifying antirheumatic drugs (csDMARDs). TNF inhibitors (TNFi) are historically proposed as the first biological DAMRD for inadequate responder patients to csDMARDs. A diverse therapeutic arsenal has become available in recent years with the development of non-anti-TNFα drugs whose mechanisms of action are different from the classical TNFi. This new biotherapy class includes tocilizumab and abatacept, two drugs recently available for subcutaneous administration that enables ambulatory care for patients who would otherwise require repeated in-hospital care.

The role of these new treatments in the therapeutic strategy has been emphasized by studies that demonstrated their efficacy as first-line treatments. However, in clinical practice, TNFi remain the most common first-line treatment for the majority of patients, non-anti-TNFα biological agents being reserved for inadequate responder patients.

In second line, several studies have investigated therapeutic strategies for inadequate responder patients to TNFi. Current data suggest that it could be wise to change the therapeutic target after failure of a first-line treatment with TNFi.

Data about the comparative efficacy of different biologics proposed after failure of a first-line treatment with TNFi are in progress. Meta-analyses from registries and academic trials conducted in France and The Netherlands suggest that non-anti-TNFα agents would have equivalent or superior efficacy compared with a second TNFi. This finding suggests clinicians to switch for an alternate therapeutic target after failure of a first-line TNFi.

Data comparing different non-anti-TNFα biologics in inadequate responder patients to TNFi are scare. Industrial trials have demonstrated sustained biological efficacy of non-anti-TNFα biologics after failure of a TNFi. However, there is very little solid data on the direct comparison between them.


Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Tocilizumab Prefilled Syringe Drug: Abatacept Prefilled Syringe Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, multicentric, randomized, open-label, superiority trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Abatacept Versus Tocilizumab by Subcutaneous Administration for the Treatment of Rheumatoid Arthritis in TNF Alpha Inhibitor Inadequate Responder Patients: A Randomized, Open-labeled, Superiority Trial
Actual Study Start Date : January 22, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tocilizumab Prefilled Syringe

Market approval recommendations will be respected. Treatment should be started within 7 days of randomization.

The treatment protocol has no specific provision for treatment adaptation. Treatment will be managed in compliance with the marketing approval recommendations and drug labeling described below.

Drug: Tocilizumab Prefilled Syringe

Treatment arm: tocilizumab (RoActemra®):

162 mg weekly a schema for therapeutic adaptation with injection intervals determined according to transaminase levels or blood cell counts (neutropenia, thrombopenia) as recommended by Roche-Chugaï (see table below).

Other Name: RoActemra

Experimental: Abatacept Prefilled Syringe

Market approval recommendations will be respected. Treatment should be started within 7 days of randomization.

The treatment protocol has no specific provision for treatment adaptation. Treatment will be managed in compliance with the marketing approval recommendations and drug labeling described below.

Drug: Abatacept Prefilled Syringe

Treatment arm: abatacept (Orencia®)

125 mg weekly after an initial dose of 500 mg (body weight <60kg), 750 mg (body weight between 60 and 100 kg), or 1000 mg (body weight >100 mg) 24 hours before the first subcutaneous injection.

Other Name: Orencia




Primary Outcome Measures :
  1. Change from baseline to 6 months of the Clinical Disease Activity Index (CDAI) [ Time Frame: 6 months ]

    The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator‟s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants.

    It will be measured at baseline and 6 months after inclusion



Secondary Outcome Measures :
  1. Change from baseline of the disease activity score [ Time Frame: 3, 6 and 12 months ]
    DAS28-ESR and DAS28-CRP: the disease activity score (DAS) is a composite score providing a numerical assessment based on the tender and swollen joint counts, the PGA VAS and the selected acute phase reactant (ESR or CRP).

  2. Change from baseline of the Clinical Disease Activity Index (CDAI) [ Time Frame: 3 and 12 months ]
    The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator‟s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants.

  3. Change from baseline of the SDAI [ Time Frame: 3, 6 and 12 months ]
    the simple disease activity index (SDAI) is a composite score providing a numerical assessment based on the tender and swollen joint count, the PGAVAS, the EGA VAS, and CRP

  4. Change from baseline in HAQ quality-of-life scores [ Time Frame: 3, 6 and 12 months ]
  5. Change from baseline in SF-36 quality-of-life scores [ Time Frame: 3, 6 and 12 months ]
  6. Change from baseline in disease self assessment [ Time Frame: 3, 6 and 12 months ]
    FLARE-RA score

  7. Change from baseline in Patient's Pain Assessment (PPA) [ Time Frame: 3, 6 and 12 months ]
  8. Change from baseline in PGA visual analogic scale (VAS) [ Time Frame: 3, 6 and 12 months ]
  9. Proportion of patients having achieved low disease activity [ Time Frame: 3, 6 and 12 months ]
    Low disease activity (LDA) is defined as DAS28-ESR<3.2 (LDA-DAS28-ESR) and CDAI<10 (LDA-CDAI)

  10. Proportion of patients in good or moderate EULAR therapeutic response [ Time Frame: 3, 6 and 12 months ]
    Good or moderate EULAR therapeutic response is defined as at least 0.6-point reduction in DAS28-ESR and final DAS28-ESR<5.1

  11. Proportion of patients achieving ACR20 response [ Time Frame: 3, 6 and 12 months ]
    ACR20 response correspond to a 20% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)

  12. Proportion of patients achieving ACR50 response [ Time Frame: 3, 6 and 12 months ]
    ACR50 responses correspond respectively to a 50% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)

  13. Proportion of patients achieving ACR70 response [ Time Frame: 3, 6 and 12 months ]
    ACR70 response correspond respectively to a 70% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)

  14. Rates of treatment persistence [ Time Frame: 3, 6 and 12 months ]
  15. Rates of patients presenting at least one adverse events [ Time Frame: 3, 6 and 12 months ]
  16. Rates of treatment withdrawals for intolerance [ Time Frame: 3, 6 and 12 months ]
  17. Rates of treatment withdrawals for intolerance requiring in-hospital care [ Time Frame: 3, 6 and 12 months ]
  18. Rates of cardiovascular events [ Time Frame: 3, 6 and 12 months ]
  19. Rates of perturbation of the lipid profile [ Time Frame: 3, 6 and 12 months ]
  20. Rates of severe infection requiring in-hospital care [ Time Frame: 3, 6 and 12 months ]
  21. Rate of rescue medication use authorized by the protocol and treatment dose of patients achieving treatment persistence [ Time Frame: 3, 6 and 12 months ]
  22. Changes in joint US-Doppler synovitis and Doppler hyperemia grade of the hands and wrists [ Time Frame: 6 months ]
  23. Changes in Sharp score in hands, wrists and feet X-Ray [ Time Frame: 12 months ]
  24. Change in vascular endothelial growth factor (VEGF) levels [ Time Frame: At 3 and 6 months ]
  25. Changes in immunoglobulin (quantitative assay) [ Time Frame: 6 months ]
  26. Changes in interleukin-6 serum levels [ Time Frame: 6 months ]


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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
  • RA according to the ACR/EULAR 2010 criteria
  • inadequate response to a subcutaneously administered first-line TNFi defined as moderate to high disease activity (DAS28-ESR>3.2 and CDAI>10) after at least 3 months of treatment with a TNFi
  • beneficiary of the French National Health Insurance Fund
  • signed informed consent form
  • for women of childbearing age: effective contraception during treatment period with engagement to continue such contraception for 14 weeks after last administration

Exclusion Criteria:

  • counter-indication for one or other of the two drugs under study
  • prior failure of the TNFi due to intolerance
  • receiving ≥15 mg/day prednisone for more than 4 weeks
  • pregnant or nursing women

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): NCT03227419


Contacts
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Contact: Amélie Lansiaux, MD, PhD 03 20 22 52 69 ext +33 lansiaux.amelie@ghicl.net
Contact: Jean-Jacques Vitagliano, PhD 03 20 22 57 51 vitagliano.jean-jacques@ghicl.net

Locations
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France
Hôpital Saint-Philibert Recruiting
Lomme, Hauts De France, France, 59462
Contact: Tristan Pascart, MD, PhD         
Principal Investigator: Tristan Pascart, MD, PhD         
Sponsors and Collaborators
Lille Catholic University
Investigators
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Principal Investigator: Pascart Tristan, MD GHICL

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Responsible Party: Lille Catholic University
ClinicalTrials.gov Identifier: NCT03227419     History of Changes
Other Study ID Numbers: RC-P0055
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Connective Tissue Diseases
Abatacept
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Autoimmune Diseases
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents