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:
SURPRISE Study Group
Information provided by:
SURPRISE Study Group
ClinicalTrials.gov Identifier:
NCT01120366
First received: May 6, 2010
Last updated: May 7, 2010
Last verified: May 2010
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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:
|
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
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 Medical Center for Rheumatic Diseases Hospital | |
| Sapporo, Hokkaido, Japan | |
| Hokkaido University 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 | |
| Tokyo Medical and Dental University Hospital Faculty of Medicine | |
| Tokyo, Japan | |
| Keio University Hospital | |
| Tokyo, Japan | |
| Institute of Rheumatology, Tokyo Women's Medical University | |
| Tokyo, Japan | |
| The University of Tokyo 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 Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Methotrexate Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs |
Pharmacologic Actions Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013