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Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation (SURPRISE)

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ClinicalTrials.gov Identifier: NCT01120366
Recruitment Status : Completed
First Posted : May 10, 2010
Last Update Posted : January 26, 2015
Sponsor:
Information provided by (Responsible Party):
SURPRISE Study Group

Tracking Information
First Submitted Date  ICMJE May 6, 2010
First Posted Date  ICMJE May 10, 2010
Last Update Posted Date January 26, 2015
Study Start Date  ICMJE October 2009
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2015)
  • DAS28-ESR remission at 24 weeks [ Time Frame: at 24 week ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • Changes over time in the number of patients maintaining discontinuation (maintenance rate) [ Time Frame: Week 52 to Week 104 ]
    Step 2: Investigation of discontinuation
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2010)
  • Incidence of Disease Activity Score (DAS) 28-ESR remission (patients achieving European League Against Rheumatism [EULAR] response-based DAS28-ESR <2.6) [ Time Frame: at 24 weeks (after treatment initiation) ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • Changes over time in the number of patients maintaining discontinuation (maintenance rate) [ Time Frame: Week 52 to Week 104 ]
    Step 2: Investigation of discontinuation
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2015)
  • Change in TSS score [ Time Frame: at 52 weeks (after treatment initiation) ]
    Step 1
  • Change of DAS28-ESR remission rate [ Time Frame: Week 0 to Week 52 ]
    Step 1
  • Change of ACR response rate [ Time Frame: Week 0 to Week 52 ]
    Step 1
  • EQ5D scores over time [ Time Frame: Week 0 to Week 52 ]
    Step 1
  • J-HAQ/HAQ scores over time [ Time Frame: Week 0 to Week 52 ]
    Step 1
  • SDAI, CDAI, and Boolean remission rates [ Time Frame: Week 0 to Week 52 ]
    Step 1
  • TNF-α over time [ Time Frame: Week 0 to Week 52 ]
    Step 1
  • Between-group comparison of the discontinuation rate after an achievement of remission [ Time Frame: Week 0 to Week 104 ]
    Step 2
  • Factor analysis of patients maintaining discontinuation [ Time Frame: Week 0 to Week 104 ]
    Step 2
  • Time course of DAS28 after restarting TCZ (between-group comparison) [ Time Frame: Week 52 to Week 104 ]
    Step 2
  • Change in TSS score [ Time Frame: Week 52 to Week 104 ]
    Step 2
  • Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1 [ Time Frame: Week 52 to Week 104 ]
    Step 2
  • SDAI, CDAI, and Boolean remission rates [ Time Frame: Week 52 to Week 104 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2010)
  • Change in total Sharp score (TSS) (the van der Heijde modified Sharp score) [ Time Frame: at 52 weeks (after treatment initiation) ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • Percentage of patients with Disease Activity Score (DAS) 28-ESR remission [ Time Frame: at 52 weeks (after treatment initiation) ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • Achievement of and changes over time in ACR20, 50, and 70, and changes over time in each component of the American College of Rheumatology (ACR) core set [ Time Frame: at Week 0, 4, 12, 24, and 52 ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • European quality of life scale (EQ5D) scores over time [ Time Frame: at Week 0, 4, 12, 24, and 52 ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • J-HAQ/HAQ scores over time [ Time Frame: at Week 0, 4, 12, 24, and 52 ]
    Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
  • Between-group comparison of the discontinuation rate after an achievement of remission [ Time Frame: at the end of the study ]
    Step 2: Investigation of discontinuation
  • Factor analysis of patients maintaining discontinuation [ Time Frame: at the end of the study ]
    Step 2: Investigation of discontinuation
  • Time course of DAS28 after restarting TCZ (between-group comparison) [ Time Frame: Week 52 to Week 104 ]
    Step 2: Investigation of discontinuation
  • Total Sharp Score [ Time Frame: Week 52 to Week 104 ]
    Step 2: Investigation of discontinuation
  • Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1 [ Time Frame: Week 52 to Week 104 ]
    Step 2: Investigation of discontinuation
Current Other Pre-specified Outcome Measures
 (submitted: January 23, 2015)
Adverse events [ Time Frame: During the study period ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
Official Title  ICMJE Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
Brief Summary

The objective of this study is to investigate the efficacy and safety of the humanized anti-human IL-6 receptor monoclonal antibody tocilizumab (TCZ) either in monotherapy or in combination therapy with methotrexate (MTX) in patients with an inadequate response to treatment with MTX.

Furthermore, in patients who have been able to achieve control of disease activity via the above therapy, we investigate the possibility of stopping TCZ and verify safety when TCZ is restarted after disease recurrence.

Detailed Description In this study, we aim to prospectively and randomly evaluate efficacy for changes in clinical remission and joint destruction in RA patients in treatment with TCZ monotherapy(SWITCH) and in combination therapy with MTX(ADD-ON), and also to investigate the best therapeutic approach to achieve discontinuation.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: Tocilizumab plus methotrexate
    Tocilizumab 8mg/kg 4weeks (i.v.) plus methotrexate up to 52weeks.The dosage of MTX will be fixed at least 24 weeks from the start of the study.
    Other Names:
    • Actemra
    • Methotrexate
  • Drug: Tocilizumab
    tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.
    Other Name: Actemra
Study Arms  ICMJE
  • Active Comparator: SWITCH
    Tocilizumab monotherapy
    Intervention: Drug: Tocilizumab
  • Active Comparator: ADD-ON
    Tocilizumab plus methotrexate combination
    Intervention: Drug: Tocilizumab plus methotrexate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 23, 2015)
233
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2010)
300
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosed with RA in accordance with the 1987 classification criteria of ACR
  • Aged 20 to 75 years inclusive at enrolment (within 2 weeks before starting treatment with the investigational drug)
  • Treated with MTX at ≥6 mg/week for at least 8 weeks immediately before enrolment
  • Rheumatoid arthritis of duration ≤10 years
  • DAS28-ESR ≥3.2 (within 2 weeks before starting treatment with the investigational drug)
  • Having received and thoroughly understood an adequate explanation about participation in the study, patients who have personally and voluntarily provided written informed consent

Major exclusion criteria:

  • Patients who were Steinbrocker Class IV.
  • Patients who received leflunomide within 12 weeks, DMARDs other than MTX within 8 weeks , or tacrolimus within 4 weeks before the 1st TCZ infusion.
  • Patients who previously received biologic DMARDs including TCZ.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01120366
Other Study ID Numbers  ICMJE SURPRISE Study
UMIN000002744 ( Other Identifier: UMIN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party SURPRISE Study Group
Study Sponsor  ICMJE SURPRISE Study Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tsutomu Takeuchi Keio University
PRS Account SURPRISE Study Group
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP