NCT01120366

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
233

participants targeted

Target at P50-P75 for phase_4 rheumatoid-arthritis

Timeline
Completed

Started Oct 2009

Longer than P75 for phase_4 rheumatoid-arthritis

Geographic Reach
1 country

30 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2009

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

May 6, 2010

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 10, 2010

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

January 26, 2015

Status Verified

January 1, 2015

Enrollment Period

5.2 years

First QC Date

May 6, 2010

Last Update Submit

January 23, 2015

Conditions

Outcome Measures

Primary Outcomes (2)

  • DAS28-ESR remission at 24 weeks

    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)

    Step 2: Investigation of discontinuation

    Week 52 to Week 104

Secondary Outcomes (13)

  • Change in TSS score

    at 52 weeks (after treatment initiation)

  • Change of DAS28-ESR remission rate

    Week 0 to Week 52

  • Change of ACR response rate

    Week 0 to Week 52

  • EQ5D scores over time

    Week 0 to Week 52

  • J-HAQ/HAQ scores over time

    Week 0 to Week 52

  • +8 more secondary outcomes

Other Outcomes (1)

  • Adverse events

    During the study period

Study Arms (2)

SWITCH

ACTIVE COMPARATOR

Tocilizumab monotherapy

Drug: Tocilizumab

ADD-ON

ACTIVE COMPARATOR

Tocilizumab plus methotrexate combination

Drug: Tocilizumab plus methotrexate

Interventions

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.

Also known as: Actemra, Methotrexate
ADD-ON

tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.

Also known as: Actemra
SWITCH

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

Hokkaido Medical Center for Rheumatic Diseases Hospital

Sapporo, Hokkaido, Japan

Location

Utazu Hama Clinic

Ayautagun, Japan

Location

Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

Bunkyō City, Japan

Location

Fukushima Red-Cross Hospital

Fukushima, Japan

Location

Higashihiroshima Memorial Hospital

Higashihiroshima, Japan

Location

Tokyo Dental College Ichikawa General Hospital

Ichikawa, Japan

Location

Itabashi Medical Center

Itabashi-ku, Japan

Location

Shimane University Faculty of Medicine

Izumo, Japan

Location

Saitama Medical Center, Saitama Medical University

Kawagoe, Japan

Location

Kagawa University

Kida-gun, Japan

Location

University of Occupational and Environmental Health Hospital

Kitakyushu, Japan

Location

Kurashiki Sweet Hospital

Kurashiki, Japan

Location

Kyoto University Graduate School of Medicine

Kyoto, Japan

Location

Marunouchi Hospital

Matsumoto, Japan

Location

Dogo Spa Hospital

Matsuyama, Japan

Location

Zenjinkai Shimin-no-mori Hospital

Miyazaki, Japan

Location

Nagasaki University Graduate School of Biomedical Sciences

Nagasaki, Japan

Location

National Hospital Organization Nagoya Medical Center

Nagoya, Japan

Location

Niigata University Graduate School of Medical and Dental Sciences

Niigata, Japan

Location

Department of Internal Medicine, Hyogo College of Medicine

Nishinomiya, Japan

Location

Oribe Rheumatism and Internal Medicine Clinic

Ōita, Japan

Location

Hokkaido University Graduate School of Medicine

Sapporo, Japan

Location

Sasebo Chuo Hospital

Sasebo, Japan

Location

Niigata Rheumatic Center

Shibata, Japan

Location

Osaka University Hospital

Suita, Japan

Location

Institute of Rheumatology, Tokyo Women's Medical University

Tokyo, Japan

Location

Keio University Hospital

Tokyo, Japan

Location

The University of Tokyo Graduate School of Medicine

Tokyo, Japan

Location

Tomishiro Chuo Hospital

Tomishiro, Japan

Location

Yokohama Minami Kyousai Hospital

Yokohama, Japan

Location

Related Publications (3)

  • 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.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumabMethotrexate

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

AminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Tsutomu Takeuchi

    Keio University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 6, 2010

First Posted

May 10, 2010

Study Start

October 1, 2009

Primary Completion

December 1, 2014

Study Completion

December 1, 2014

Last Updated

January 26, 2015

Record last verified: 2015-01

Locations