Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation - Full Text View

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	Phase
Rheumatoid Arthritis	Drug: Tocilizumab plus methotrexate Drug: Tocilizumab	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Success of Tocilizumab in RA Patients With Remission Induction and Sustained Efficacy After Discontinuation

Resource links provided by NLM:

Genetics Home Reference related topics: rheumatoid arthritis

Drug Information available for: Methotrexate Methotrexate sodium Tocilizumab

U.S. FDA Resources

Further study details as provided by SURPRISE Study Group:

Primary Outcome Measures:

DAS28-ESR remission at 24 weeks [ Time Frame: at 24 week ] [ 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: No ]
Step 2: Investigation of discontinuation

Secondary Outcome Measures:

Change in TSS score [ Time Frame: at 52 weeks (after treatment initiation) ] [ Designated as safety issue: No ]
Step 1
Change of DAS28-ESR remission rate [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
Step 1
Change of ACR response rate [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
Step 1
EQ5D scores over time [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
Step 1
J-HAQ/HAQ scores over time [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
Step 1
SDAI, CDAI, and Boolean remission rates [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
Step 1
TNF-α over time [ Time Frame: Week 0 to Week 52 ] [ Designated as safety issue: No ]
Step 1
Between-group comparison of the discontinuation rate after an achievement of remission [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
Step 2
Factor analysis of patients maintaining discontinuation [ Time Frame: Week 0 to Week 104 ] [ Designated as safety issue: No ]
Step 2
Time course of DAS28 after restarting TCZ (between-group comparison) [ Time Frame: Week 52 to Week 104 ] [ Designated as safety issue: No ]
Step 2
Change in TSS score [ Time Frame: Week 52 to Week 104 ] [ Designated as safety issue: No ]
Step 2
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
SDAI, CDAI, and Boolean remission rates [ Time Frame: Week 52 to Week 104 ] [ Designated as safety issue: No ]

Other Outcome Measures:

Adverse events [ Time Frame: During the study period ] [ Designated as safety issue: Yes ]


Enrollment:	233
Study Start Date:	October 2009
Study Completion Date:	December 2014
Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: SWITCH Tocilizumab monotherapy	Drug: Tocilizumab tocilizumab 8mg/kg/4weeks (i.v.) up to 52weeks. Other Name: 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

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.

Eligibility


Ages Eligible for Study:	20 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

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

Sponsors and Collaborators

SURPRISE Study Group

Investigators


Principal Investigator:	Tsutomu Takeuchi	Keio University

More Information


Responsible Party:	SURPRISE Study Group
ClinicalTrials.gov Identifier:	NCT01120366 History of Changes
Other Study ID Numbers:	SURPRISE Study UMIN000002744
Study First Received:	May 6, 2010
Last Updated:	January 23, 2015
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:


Arthritis, Rheumatoid Arthritis 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 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 September 27, 2016

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