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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
SURPRISE Study Group
ClinicalTrials.gov Identifier:
NCT01120366
First received: May 6, 2010
Last updated: May 7, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention
Rheumatoid Arthritis
Drug: Tocilizumab plus methotrexate
Drug: Tocilizumab

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy Comparison of Tocilizumab Monotherapy and Tocilizumab Plus Methotrexate Combination Therapy in Rheumatoid Arthritis, and Discontinuation of Tocilizumab

Resource links provided by NLM:


Further study details as provided by SURPRISE Study Group:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Step 2: Investigation of discontinuation


Secondary Outcome Measures:
  • Change in total Sharp score (TSS) (the van der Heijde modified Sharp score) [ Time Frame: at 52 weeks (after treatment initiation) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Step 2: Investigation of discontinuation

  • Factor analysis of patients maintaining discontinuation [ Time Frame: at the end of the study ] [ Designated as safety issue: No ]
    Step 2: Investigation of discontinuation

  • Time course of DAS28 after restarting TCZ (between-group comparison) [ Time Frame: Week 52 to Week 104 ] [ Designated as safety issue: Yes ]
    Step 2: Investigation of discontinuation

  • Total Sharp Score [ Time Frame: Week 52 to Week 104 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Step 2: Investigation of discontinuation


Estimated Enrollment: 300
Study Start Date: October 2009
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: TCZ Group
Tocilizumab monotherapy
Drug: Tocilizumab
tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks.
Other Name: Actemra
Active Comparator: MTX+TCZ Group
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with RA in accordance with the 1987 classification criteria of the American College of Rheumatology (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

Exclusion Criteria:

  • Evaluated with functional activity in Steinbrocker Class IV within 4 weeks before starting treatment with the investigational drug
  • Treated with leflunomide within 12 weeks, any DMARD other than MTX within 8 weeks, or immunosuppressants such as tacrolimus within 4 weeks before starting treatment with the investigational drug (prohibited concomitant treatments)
  • History of treatment with any biological product
  • Received any of the following within 4 weeks before starting treatment with the investigational drug

    • Corticosteroid hormone products exceeding a prednisolone-equivalent dose of 10 mg/day
    • Increased dose or new administration of corticosteroid hormone product
    • Plasmapheresis
    • Surgical treatment such as joint replacement procedure, that could potentially affect assessment of efficacy
  • Laboratory values corresponding to any of the following within 2 weeks before starting treatment with the investigational drug

    • Peripheral leukocyte count <4,000/μL
    • Peripheral lymphocyte count <1,000/μL
    • Positive β-D glucan in blood
  • Coexisting chronic active Epstein-Barr virus infection
  • Coexisting hepatitis B infection
  • Patients with frank infection immediately before the start of treatment with the investigational drug who are judged unsuitable by the investigator or sub-investigator
  • Women who are pregnant, breastfeeding, possibly pregnant, or women who wish to become pregnant or their male partners
  • Patients who are otherwise judged by the investigator to be unsuitable on medical grounds
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01120366

Locations
Japan
Nagoya National Hospital
Nagoya, Aichi, Japan
Dogo Spa Hospital
Matsuyama, Ehime, Japan
University of Occupational and Environmental Health Hospital
Kitakyusyu, Fukuoka, Japan
Higashihiroshima Memorial Hospital
Higashihiroshima, Hiroshima, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, Japan
Hokkaido Medical Center for Rheumatic Diseases Hospital
Sapporo, Hokkaido, Japan
Utazuhama Clinic
Ayautagun, Kagawa, Japan
Kagawa University Hospital
Kida-gun, Kagawa, Japan
Marunouchi Hospital
Matsumoto, Nagano, Japan
Sasebo Chuo Hospital
Sasebo, Nagasaki, Japan
Kurashiki Kosai Hospital
Kurashiki, Okayama, Japan
Tomishiro Chuo Hospital
Tomishiro, Okinawa, Japan
Osaka University Hospital
Suita, Osaka, Japan
Saitama Medical School
Kawagoe, Saitama, Japan
Shimane University Hospital
Izumo, Shimane, Japan
Fukushima Red Cross Hospital
Fukushima, Japan
Kyoto University Hospital
Kyoto, Japan
Nagasaki University Hospital
Nagasaki, Japan
Niigata University Medical & Dental Hospital
Niigata, Japan
Institute of Rheumatology, Tokyo Women's Medical University
Tokyo, Japan
The University of Tokyo Hospital
Tokyo, Japan
Tokyo Medical and Dental University Hospital Faculty of Medicine
Tokyo, Japan
Keio University Hospital
Tokyo, Japan
Sponsors and Collaborators
SURPRISE Study Group
Investigators
Principal Investigator: Tsutomu Takeuchi Keio University
  More Information

No publications provided

Responsible Party: Tsutomu Takeuchi, Keio University
ClinicalTrials.gov Identifier: NCT01120366     History of Changes
Other Study ID Numbers: SURPRISE Study, UMIN000002744
Study First Received: May 6, 2010
Last Updated: May 7, 2010
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014