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

January 23, 2015 updated by: SURPRISE Study Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

233

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Ayautagun, Japan
        • Utazu Hama Clinic
      • Bunkyo-ku, Japan
        • Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
      • Fukushima, Japan
        • Fukushima Red-Cross Hospital
      • Higashihiroshima, Japan
        • Higashihiroshima Memorial Hospital
      • Ichikawa, Japan
        • Tokyo Dental College Ichikawa General Hospital
      • Itabashi-ku, Japan
        • Itabashi Medical Center
      • Izumo, Japan
        • Shimane University Faculty of Medicine
      • Kawagoe, Japan
        • Saitama Medical Center, Saitama Medical University
      • Kida-gun, Japan
        • Kagawa University
      • Kitakyusyu, Japan
        • University of Occupational and Environmental Health Hospital
      • Kurashiki, Japan
        • Kurashiki Sweet Hospital
      • Kyoto, Japan
        • Kyoto University Graduate School of Medicine
      • Matsumoto, Japan
        • Marunouchi Hospital
      • Matsuyama, Japan
        • Dogo Spa Hospital
      • Miyazaki, Japan
        • Zenjinkai Shimin-no-mori Hospital
      • Nagasaki, Japan
        • Nagasaki University Graduate School of Biomedical Sciences
      • Nagoya, Japan
        • National Hospital Organization Nagoya Medical Center
      • Niigata, Japan
        • Niigata University Graduate School of Medical and Dental Sciences
      • Nishinomiya, Japan
        • Department of Internal Medicine, Hyogo College of Medicine
      • Oita, Japan
        • Oribe Rheumatism and Internal Medicine Clinic
      • Sapporo, Japan
        • Hokkaido University Graduate School of Medicine
      • Sasebo, Japan
        • Sasebo Chuo Hospital
      • Shibata, Japan
        • Niigata Rheumatic Center
      • Suita, Japan
        • Osaka University Hospital
      • Tokyo, Japan
        • Keio University Hospital
      • Tokyo, Japan
        • Institute of Rheumatology, Tokyo Women's Medical University
      • Tokyo, Japan
        • The University of Tokyo Graduate School of Medicine
      • Tomishiro, Japan
        • Tomishiro Chuo Hospital
      • Yokohama, Japan
        • Yokohama Minami Kyousai Hospital
    • Hokkaido
      • Sapporo, Hokkaido, Japan
        • Hokkaido Medical Center for Rheumatic Diseases Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: SWITCH
Tocilizumab monotherapy
Drug: Tocilizumab
tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.
Other Names:
  • Actemra
Active Comparator: ADD-ON
Tocilizumab plus methotrexate combination
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
at 24 week
Changes over time in the number of patients maintaining discontinuation (maintenance rate)
Time Frame: Week 52 to Week 104
Step 2: Investigation of discontinuation
Week 52 to Week 104

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in TSS score
Time Frame: at 52 weeks (after treatment initiation)
Step 1
at 52 weeks (after treatment initiation)
Change of DAS28-ESR remission rate
Time Frame: Week 0 to Week 52
Step 1
Week 0 to Week 52
Change of ACR response rate
Time Frame: Week 0 to Week 52
Step 1
Week 0 to Week 52
EQ5D scores over time
Time Frame: Week 0 to Week 52
Step 1
Week 0 to Week 52
J-HAQ/HAQ scores over time
Time Frame: Week 0 to Week 52
Step 1
Week 0 to Week 52
SDAI, CDAI, and Boolean remission rates
Time Frame: Week 0 to Week 52
Step 1
Week 0 to Week 52
TNF-α over time
Time Frame: Week 0 to Week 52
Step 1
Week 0 to Week 52
Between-group comparison of the discontinuation rate after an achievement of remission
Time Frame: Week 0 to Week 104
Step 2
Week 0 to Week 104
Factor analysis of patients maintaining discontinuation
Time Frame: Week 0 to Week 104
Step 2
Week 0 to Week 104
Time course of DAS28 after restarting TCZ (between-group comparison)
Time Frame: Week 52 to Week 104
Step 2
Week 52 to Week 104
Change in TSS score
Time Frame: Week 52 to Week 104
Step 2
Week 52 to Week 104
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
Week 52 to Week 104
SDAI, CDAI, and Boolean remission rates
Time Frame: Week 52 to Week 104
Week 52 to Week 104

Other Outcome Measures

Outcome Measure
Time Frame
Adverse events
Time Frame: During the study period
During the study period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SURPRISE Study Group

Investigators

  • Principal Investigator: Tsutomu Takeuchi, Keio University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

May 6, 2010

First Submitted That Met QC Criteria

May 7, 2010

First Posted (Estimate)

May 10, 2010

Study Record Updates

Last Update Posted (Estimate)

January 26, 2015

Last Update Submitted That Met QC Criteria

January 23, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SURPRISE Study
  • UMIN000002744 (Other Identifier: UMIN)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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