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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Tocilizumab plus methotrexate
Tocilizumab
Sponsored by
SURPRISE Study Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

SWITCH

ADD-ON

Arm Description

Tocilizumab monotherapy

Tocilizumab plus methotrexate combination

Outcomes

Primary Outcome Measures

DAS28-ESR remission at 24 weeks
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)
Step 2: Investigation of discontinuation

Secondary Outcome Measures

Change in TSS score
Step 1
Change of DAS28-ESR remission rate
Step 1
Change of ACR response rate
Step 1
EQ5D scores over time
Step 1
J-HAQ/HAQ scores over time
Step 1
SDAI, CDAI, and Boolean remission rates
Step 1
TNF-α over time
Step 1
Between-group comparison of the discontinuation rate after an achievement of remission
Step 2
Factor analysis of patients maintaining discontinuation
Step 2
Time course of DAS28 after restarting TCZ (between-group comparison)
Step 2
Change in TSS score
Step 2
Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1
Step 2
SDAI, CDAI, and Boolean remission rates

Full Information

First Posted
May 6, 2010
Last Updated
January 23, 2015
Sponsor
SURPRISE Study Group
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1. Study Identification

Unique Protocol Identification Number
NCT01120366
Brief Title
Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
Acronym
SURPRISE
Official Title
Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SURPRISE Study Group

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
233 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SWITCH
Arm Type
Active Comparator
Arm Description
Tocilizumab monotherapy
Arm Title
ADD-ON
Arm Type
Active Comparator
Arm Description
Tocilizumab plus methotrexate combination
Intervention Type
Drug
Intervention Name(s)
Tocilizumab plus methotrexate
Other Intervention Name(s)
Actemra, Methotrexate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
Actemra
Intervention Description
tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.
Primary Outcome Measure Information:
Title
DAS28-ESR remission at 24 weeks
Description
Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX
Time Frame
at 24 week
Title
Changes over time in the number of patients maintaining discontinuation (maintenance rate)
Description
Step 2: Investigation of discontinuation
Time Frame
Week 52 to Week 104
Secondary Outcome Measure Information:
Title
Change in TSS score
Description
Step 1
Time Frame
at 52 weeks (after treatment initiation)
Title
Change of DAS28-ESR remission rate
Description
Step 1
Time Frame
Week 0 to Week 52
Title
Change of ACR response rate
Description
Step 1
Time Frame
Week 0 to Week 52
Title
EQ5D scores over time
Description
Step 1
Time Frame
Week 0 to Week 52
Title
J-HAQ/HAQ scores over time
Description
Step 1
Time Frame
Week 0 to Week 52
Title
SDAI, CDAI, and Boolean remission rates
Description
Step 1
Time Frame
Week 0 to Week 52
Title
TNF-α over time
Description
Step 1
Time Frame
Week 0 to Week 52
Title
Between-group comparison of the discontinuation rate after an achievement of remission
Description
Step 2
Time Frame
Week 0 to Week 104
Title
Factor analysis of patients maintaining discontinuation
Description
Step 2
Time Frame
Week 0 to Week 104
Title
Time course of DAS28 after restarting TCZ (between-group comparison)
Description
Step 2
Time Frame
Week 52 to Week 104
Title
Change in TSS score
Description
Step 2
Time Frame
Week 52 to Week 104
Title
Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1
Description
Step 2
Time Frame
Week 52 to Week 104
Title
SDAI, CDAI, and Boolean remission rates
Time Frame
Week 52 to Week 104
Other Pre-specified Outcome Measures:
Title
Adverse events
Time Frame
During the study period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tsutomu Takeuchi
Organizational Affiliation
Keio University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hokkaido Medical Center for Rheumatic Diseases Hospital
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Utazu Hama Clinic
City
Ayautagun
Country
Japan
Facility Name
Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
City
Bunkyo-ku
Country
Japan
Facility Name
Fukushima Red-Cross Hospital
City
Fukushima
Country
Japan
Facility Name
Higashihiroshima Memorial Hospital
City
Higashihiroshima
Country
Japan
Facility Name
Tokyo Dental College Ichikawa General Hospital
City
Ichikawa
Country
Japan
Facility Name
Itabashi Medical Center
City
Itabashi-ku
Country
Japan
Facility Name
Shimane University Faculty of Medicine
City
Izumo
Country
Japan
Facility Name
Saitama Medical Center, Saitama Medical University
City
Kawagoe
Country
Japan
Facility Name
Kagawa University
City
Kida-gun
Country
Japan
Facility Name
University of Occupational and Environmental Health Hospital
City
Kitakyusyu
Country
Japan
Facility Name
Kurashiki Sweet Hospital
City
Kurashiki
Country
Japan
Facility Name
Kyoto University Graduate School of Medicine
City
Kyoto
Country
Japan
Facility Name
Marunouchi Hospital
City
Matsumoto
Country
Japan
Facility Name
Dogo Spa Hospital
City
Matsuyama
Country
Japan
Facility Name
Zenjinkai Shimin-no-mori Hospital
City
Miyazaki
Country
Japan
Facility Name
Nagasaki University Graduate School of Biomedical Sciences
City
Nagasaki
Country
Japan
Facility Name
National Hospital Organization Nagoya Medical Center
City
Nagoya
Country
Japan
Facility Name
Niigata University Graduate School of Medical and Dental Sciences
City
Niigata
Country
Japan
Facility Name
Department of Internal Medicine, Hyogo College of Medicine
City
Nishinomiya
Country
Japan
Facility Name
Oribe Rheumatism and Internal Medicine Clinic
City
Oita
Country
Japan
Facility Name
Hokkaido University Graduate School of Medicine
City
Sapporo
Country
Japan
Facility Name
Sasebo Chuo Hospital
City
Sasebo
Country
Japan
Facility Name
Niigata Rheumatic Center
City
Shibata
Country
Japan
Facility Name
Osaka University Hospital
City
Suita
Country
Japan
Facility Name
Institute of Rheumatology, Tokyo Women's Medical University
City
Tokyo
Country
Japan
Facility Name
Keio University Hospital
City
Tokyo
Country
Japan
Facility Name
The University of Tokyo Graduate School of Medicine
City
Tokyo
Country
Japan
Facility Name
Tomishiro Chuo Hospital
City
Tomishiro
Country
Japan
Facility Name
Yokohama Minami Kyousai Hospital
City
Yokohama
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
31106666
Citation
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.
Results Reference
derived
PubMed Identifier
29853455
Citation
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.
Results Reference
derived
PubMed Identifier
26733110
Citation
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.
Results Reference
derived

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

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