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

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

Tracking Information

• First Submitted Date: May 6, 2010
• First Posted Date: May 10, 2010
• Last Update Posted Date: January 26, 2015
• Study Start Date: October 2009
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• 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

• Active Comparator: SWITCH
  Tocilizumab monotherapy
  Intervention: Drug: Tocilizumab
• Active Comparator: ADD-ON
  Tocilizumab plus methotrexate combination
  Intervention: Drug: Tocilizumab plus methotrexate

Publications *

• Kato M, Kaneko Y, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Nagasawa H, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Yokota I, Atsumi T, Takeuchi T. Predictive value of serum amyloid a levels for requirement of concomitant methotrexate in tocilizumab initiation: A post hoc analysis of the SURPRISE study. Mod Rheumatol. 2020 May;30(3):442-449. doi: 10.1080/14397595.2019.1621026. Epub 2019 Jun 7.
• Kaneko Y, Kato M, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Takeuchi T; SURPRISE study group. Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study). Ann Rheum Dis. 2018 Sep;77(9):1268-1275. doi: 10.1136/annrheumdis-2018-213416. Epub 2018 May 31.
• Kaneko Y, Atsumi T, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Nagasawa H, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Takeuchi T. Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study). Ann Rheum Dis. 2016 Nov;75(11):1917-1923. doi: 10.1136/annrheumdis-2015-208426. Epub 2016 Jan 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 23, 2015): 233
• Original Estimated Enrollment (submitted: May 7, 2010): 300
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01120366
• Other Study ID Numbers: SURPRISE Study; UMIN000002744 ( Other Identifier: UMIN )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: SURPRISE Study Group
• Study Sponsor: SURPRISE Study Group
• Collaborators: Not Provided

Investigators

• Principal Investigator: Tsutomu Takeuchi; Keio University

• PRS Account: SURPRISE Study Group
• Verification Date: January 2015