UMIN-CTR Clinical Trial

Public title

Clinical trial of Tocilizumab for adult onset still disease

Acronym

Clinical trial of Tocilizumab for adult onset still disease

Scientific Title

Clinical trial of Tocilizumab for adult onset still disease

Scientific Title:Acronym

Clinical trial of Tocilizumab for adult onset still disease

Region

Japan

Condition

Adult onset still diseas

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Yuko Kaneko

Organization

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

Division name

Division of Rheumatology

Zip code

Address

35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582

TEL

03-3353-1211

Email

ykaneko@z6.keio.jp

Name of contact person

1st name
Middle name
Last name	Yuto Fujiki

Organization

Keio University Hospital

Division name

Clinical and Translational Research Center

Zip code

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

Institute

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

Institute

Department

Personal name

Organization

Minister of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2014

Year

01

Month

31

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

11

Month

28

Day

Date of IRB

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

Other related information

Registered date

2014

Year

01

Month

28

Day

Last modified on

2018

Year

02

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015169