UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Clinical trial of Tocilizumab for adult onset still disease
Title of the study (Brief title)	Clinical trial of Tocilizumab for adult onset still disease
Region	Japan

Condition
Condition	Adult onset still diseas
Classification by specialty	Clinical immunology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To assess the efficacy, safety and pharmacokinetics of Tocilizumab by placebo-controlled trial
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	[Double blind phase(Part1,2)] Part1:Proportion of Patients who achieved ACR 50% improvement at 4 weeks. Part2:Proportion of Patients who achieved ACR 50% improvement at 12 weeks [Open phase (part3)] Proportion of Patients who achieved ACR 50% improvement and whose corticosteroid level is 5mg/day or less at least 7 days before 52 weeks
Key secondary outcomes	[Efficacy] (Double blind phase(Part1,2)) *Decrease rate of corticosteroid at 12 weeks *Change of ACR20% and 50%, 70% improvement until 12 weeks *Change of SFS until 12 weeks *Change of ACR core set until 12 weeks *Absence of fever until 12 weeks *Absence of rash until 12 weeks *Change of serum ferritin until 12 weeks *Proportion of patients who achieved ACR 50% improvement and do not have fever at 12 weeks, and whose dose of corticosteroid decreased by over 20% *Proportion of patients with over 2-point decrease in SFS including a decrease in at least 1 of clinical variables at 4 weeks *Proportion of patients with over 2-point decrease in SFS including a decrease in at least 1 of clinical variables at 12 weeks (Open phase(part3)) *Proportion of patients with over 2-point decrease in SFS including a decrease in at least 1 of clinical variables at 52 weeks *Proportion of patients who achieved discontinuation of corticosteroid at 52 weeks *Changes of ACR 20%, 50% and 70% improvement at 52 weeks *Change of SFS at 52 weeks *Change of ACR core set at 52 weeks *Absence of fever at 52 weeks *Absence of rash at 52 weeks *Change of serum ferritin at 52 weeks *Decrease rate of and change in dose of corticosteroid at 52 weeks [Safety] Adverse event [PK] Serum Tocilizumab level, CRP, ESR, sIL-6 receptor

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	YES
Concealment	No need to know

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Tocilizumab
Interventions/Control_2	Placebo
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Patients with adult onset still disease diagnosed according to classification criteria by Yamaguchi(1992) 2) Patients aged 20 or older 3) Patients diagnosed over 16 years old 4) Patients whose response to over 0.5mg/kg/day corticosteroid are insufficient, and who have received more than 10mg/day corticosteroid over 2 weeks before participating in this trial 5) Numbers of tender and swollen joints are 2 or more, and Patient with over 1 point in SFS 6) ESR(Westergren) =>20 mm/hr or CRP =>10 mg/L 7) Patients whose written informed consent has been obtained
Key exclusion criteria	1) Patients having received Inflixmab, Golimumab, Adalimumab, Apatacept, Leflunomide and Certolizumab pegol within 12 weeks 2) Patients having received Etanercept within weeks before starting treatment 3) Patients having received surgical treatment or plasmapheresis within 4 weeks before starting treatment 4) Patients having received DMARDs or immune-suppressing drug within 2 weeks 5) Patients having changing the dose of corticosteroid within 2 weeks 6) Patients having received cell depletion therapy before participation in this study 7) White blood cell count <3x10^9/L 8) Neutrophil count <1,000/microliter 9) Platelet count <50x10^9/L 10) Lymphocyte count <500/microliter 11) ALP >five times of upper limit of facility criteria 12) Total Bilirubin >three times of upper limit of facility criteria 13) Patients with past history of serious allergy 14) Patients with drug allergy for Tocilizumab 15) Patients with serious disease 16) Patients with active tuberculosis 17) Patients with interstitial pneumonia 18) Patients with past history of HIV, hepatitis B and hepatitis C 19) Patients having received live vaccine within 6 weeks before treatment 20) Patients who have been diagnosed cancer within 5 years 21) Patients with current and past history of intestinal diverticulum 22) Patients with infection within 4 weeks 23) Patients having received the other drug within 6 months 24) Patients who cannot receive intravenous therapy 25) Patients with current history of alcoholics and drug dependence, or with past history of alcoholics and drug dependence within 24 weeks 26) Patients with a history of receiving Tocilizumab 27) Expecting mothers or mothers with breast-feeding 28) Patients who will not use any way of contraception 29) Others not applicable person determined by a doctor
Target sample size	34

Research contact person
Name of lead principal investigator	Yuko Kaneko
Organization	Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine
Division name	Division of Rheumatology
Address	35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582
TEL	03-3353-1211
Email	ykaneko@z6.keio.jp

Public contact
Name of contact person	Yuto Fujiki
Organization	Keio University Hospital
Division name	Clinical and Translational Research Center
Address	Clinical Research Building #111, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582
TEL	03-5315-4278
Homepage URL
Email	pmo@ccr.med.keio.ac.jp

Sponsor
Institute	Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine
Institute
Department

Funding Source
Organization	Minister of Health, Labour and Welfare
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	慶應義塾大学病院（東京都）、北海道大学病院（北海道）、東北大学病院（宮城県）、筑波大学医学部附属病院（茨城県）、千葉大学医学部附属病院（千葉県）、京都大学医学部附属病院（京都府）、大阪大学医学部附属病院（大阪府）、産業医科大学病院（福岡県）

Other administrative information
Date of disclosure of the study information	2014 Year 01 Month 31 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 11 Month 28 Day
Anticipated trial start date	2014 Year 01 Month 31 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2014 Year 01 Month 28 Day
Last modified on	2018 Year 02 Month 17 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015169