Exploratory study to evaluate the efficacy and safety of tocilizumab for Takayasu's arteritis based on classification by type of autoantibody

JRCT ID: jRCTs021210077

Registered date:22/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Takayasu's arteritis;TA
• Date of first enrollment: 01/08/2022
• Target sample size: 20
• Study type: Interventional

Intervention(s)

(1) In all cases, tocilizumab 162 mg should be subcutaneously administered once a week and continued for 6 months (24 weeks) during the study period.
(2) After registration, reduce the dose of steroids according to the administration schedule.

Outcome(s)

• Primary Outcome: Difference in achievement rate of A remission among various pathological conditions according to autoantibody classification (anti-EPCR antibody positive, anti-SR-BI antibody positive, both antibody negative) at 24 weeks after registration (A remission: disappearance of inflammatory findings and steroid discontinuation)

Secondary Outcome

(1) Difference in achievement rate of C remission among various pathological conditions by autoantibody classification at 16 weeks after registration (C remission: elimination of inflammatory findings and reduction of steroid drug dose to 5 mg / day or less in terms of prednisolone)
(2) Difference in achievement rate of B remission between various pathological conditions by autoantibody classification in 20 weeks after registration (B remission: elimination of inflammatory findings and reduction of steroid drug dose to 2.5 mg / day or less in terms of prednisolone)
(3) Differences between various pathological conditions due to autoantibody classification of steroid amount at the time of recurrence
(4) Differences between various pathological conditions due to autoantibody classification of the amount of steroid administered 24 weeks after registration
(5) Difference in symptom disappearance rate between various pathological conditions by autoantibody classification 24 weeks after registration
(6) Differences between various pathological conditions by autoantibody classification of the following items at 12, 16, 20 and 24 weeks after registration
- Relapse rate
- Whether or not the administration of immunosuppressants is started
- Presence / absence of increase / decrease of symptomatic treatment for systemic symptoms
(7)Transition from baseline of the following immunological test items to 24 weeks after registration
- CRP, erythrocyte sedimentation rate, blood IL-6 concentration, antibody titer of autoantibodies (anti-EPCR antibody, anti-SR-BI antibody)
(8) Presence or absence of changes in CT findings from baseline 24 weeks after registration
(9) Safety endpoints: adverse events, laboratory test values, vital signs

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all of the following conditions (1) to (5)
1) Patients over 20 years old (at the time of consent)
2) Patients diagnosed with Takayasu's arteritis according to any of the following criteria at the time of registration. It does not matter whether tocilizumab is used or not.
1.2017 Ministry of Health, Labor and Welfare Takayasu's Arteritis Diagnostic Criteria
2.American Rheumatology Society (ACR) ,Takayasu's Arteritis Diagnostic Criteria (1990)
3) Patients with no inflammatory findings of Takayasu's arteritis at the time of registration
4) Patients whose steroid dose at the time of registration can be reduced to 20 mg / day or less in terms of prednisolone.
5) Patients who can confirm the history of recurrence on the medical record under the administration of steroids with prednisolone equivalent of 7.5 mg / day or more. It is assumed that any of the following is present as a necessary symptom or finding as a recurrence symptom.
Headache, dizziness, systemic symptoms (fever, malaise, weight loss, joint symptoms, muscle symptoms, etc.), vascular lesions and associated symptoms, CRP persistent positive

Exclude criteria

Check the following at the time of registration and exclude patients who fall under any of the following. Regarding the confirmation of the criteria corresponding to (4) to (9), If there is a clinical test result conducted within 4 weeks (28 days) before registration (Day 1), even if it is a test performed before obtaining consent, it is possible to judge from the result.
1) Patients who received new or increased doses of immunosuppressive agents other than steroids within 4 weeks (28 days) before registration
2) Patients who received biologics other than tocilizumab and rituximab (anti-TNF-alpha preparation, abatacept, anti-IL-6 receptor preparation, etc.) within 3 months (12 weeks) before registration.
3) Patients who received rituximab within 6 months (24 weeks) before enrollment
4) Patients with severe renal impairment (nephrotic syndrome, serum creatinine of 2.5 mg / dL or higher)
5) Patients with severe liver dysfunction (child classification B or higher)
6) Patients with severe cardiac dysfunction (ischemic heart disease, heart failure) or findings requiring treatment on electrocardiogram / echocardiography
7) Patients with drug-resistant hypertension
8) Patients with malignant tumor or history of malignant tumor (excluding cases without recurrence for 5 years or more)
9) HBsAg positive, HIV positive, HCV positive patients
10) Patients with serious infections
11) Pregnant or lactating women and women wishing to become pregnant during the study period
12) Patients who have participated in clinical trials such as clinical trials using unapproved drugs or new drugs or post-marketing clinical trials within the past 6 months
13) In addition, patients who are judged to be inappropriate for inclusion in this study by the investigator / responsible physician (hereinafter referred to as the investigator, etc.)

Related Information

• Primary Sponsor: Ishii Tomonori
• Source(s) of Monetary Support: Chugai Pharmaceutical Co., Ltd.