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

Rheumatoid Arthritis Clinical Trial

— SURPRISE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01120366
• Other study ID #: SURPRISE Study
• Secondary ID: UMIN000002744
• Status: Completed
• Phase: Phase 4
• First received: May 6, 2010
• Last updated: January 23, 2015
• Start date: October 2009
• Est. completion date: December 2014

Study information

• Verified date: January 2015
• Source: SURPRISE Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 233
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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

Locations

Country	Name	City	State
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 Medical Center for Rheumatic Diseases Hospital	Sapporo	Hokkaido
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

Sponsors (1)

Lead Sponsor	Collaborator
SURPRISE Study Group

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events		During the study period	Yes
Primary	DAS28-ESR remission at 24 weeks	Step 1: Investigation of the efficacy and safety of TCZ in combination therapy with MTX	at 24 week	No
Primary	Changes over time in the number of patients maintaining discontinuation (maintenance rate)	Step 2: Investigation of discontinuation	Week 52 to Week 104	No
Secondary	Change in TSS score	Step 1	at 52 weeks (after treatment initiation)	No
Secondary	Change of DAS28-ESR remission rate	Step 1	Week 0 to Week 52	No
Secondary	Change of ACR response rate	Step 1	Week 0 to Week 52	No
Secondary	EQ5D scores over time	Step 1	Week 0 to Week 52	No
Secondary	J-HAQ/HAQ scores over time	Step 1	Week 0 to Week 52	No
Secondary	SDAI, CDAI, and Boolean remission rates	Step 1	Week 0 to Week 52	No
Secondary	TNF-a over time	Step 1	Week 0 to Week 52	No
Secondary	Between-group comparison of the discontinuation rate after an achievement of remission	Step 2	Week 0 to Week 104	No
Secondary	Factor analysis of patients maintaining discontinuation	Step 2	Week 0 to Week 104	No
Secondary	Time course of DAS28 after restarting TCZ (between-group comparison)	Step 2	Week 52 to Week 104	No
Secondary	Change in TSS score	Step 2	Week 52 to Week 104	No
Secondary	Time course of DAS28 after restarting MTX following suspension of discontinuation in the TCZ monotherapy group in Step 1	Step 2	Week 52 to Week 104	No
Secondary	SDAI, CDAI, and Boolean remission rates		Week 52 to Week 104	No