Takayasu Arteritis Clinical Trial in China (TACTIC)

This is an interventional treatment trial for Takayasu Arteritis focused on measuring Takayasu Arteritis, Leflunomide Read More

Inclusion Criteria:

1. Signed informed consent form;

2. Subjects who met the American College of Rheumatology 1990 classification criteria for Takayasu arteritis:

   2.1 Age of onset ≤40 years; 2.2 Claudication of upper or lower extremities; 2.3 Decreased pulsation of 1 or both brachial arteries; 2.4 Difference of ≥ 10 mmHg in systolic blood pressure between arms; 2.5 Bruit over subclavian arteries or aorta; 2.6 Angiography * showing a branch of the aorta stenosis or occlusion; Meeting more than 3 of 6 criteria suggests the diagnosis of Takayasu arteritis.

   * Angiography in this study was replaced by vascular magnetic resonance angiography（MRA）or computed tomography angiography（CTA）.

3. Males or females between the ages of 18 and 65 years;
4. All subjects agreed to have no childbearing plan during the clinical trial, and the results of serum or urine pregnancy test for females must be negative;

5. Evidence of disease in active phase during the past 3 months, meeting at least 2 of the following criteria:

   5.1 There is a new onset of vascular ischemia ,in accordance with at least one of the following:

   5.1.1 newly discovered difference of blood pressure between arms (systolic pulse pressure difference of at least ≥ 10mmHg);

   5.1.2 new onset of decreased pulsation of 1 or both brachial arteries;

   5.1.3 other new manifestations of vascular ischemia;

   5.2 Inflammatory abnormalities, meeting at least one of the following:

   5.2.1 Erythrocyte sedimentation rate（ESR） level higher than the normal upper limit（others factors like infection are excluded）;

   5.2.2 high-sensitivity C-reactive protein（hsCRP）≥ 6mg/L or C-reactive protein（CRP）> 10mg/L;

   5.3 Imaging examinations show abnormalities suggesting that disease is in active phase, meeting at least one of the following: 5.3.1 Vascular wall show enhanced signal on MRA(active inflammation);

   5.3.2 enhanced CTA suggests new vascular lesions;

   5.3.3 Color Doppler ultrasonography suggests vascular wall inflammation;

   5.3.4 PET/CT suggests elevated SUV value on vascular wall;

   5.4 Systemic symptoms that can not be explained by other causes: fever, fatigue or losing weight.

6. If the patient is taking prednisone or its equivalent before screening, the dose should not exceed 0.6mg/kg/d and keep stable for at least 4 weeks before the first dose of the trial treatment;
7. If the patient has previously received medication for Takayasu Arteritis, the withdrawal time before first dose of the trial treatment should meet:

7.1 Leflunomide: ≥ 6 months. If cholestyramine is used at least for 11 days, the withdrawal time required ≥ 4 weeks;

7.2 Cyclophosphamide ≥ 8 weeks;

7.3 Azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, thalidomide, antimalarial or any other medication for Takayasu arteritis but not specifically allowed during the trial was not taken when the first dose of trial drugs were given;

7.4 Biological agents such as rituximab, IL-6 receptor antagonists, tumor necrosis factor inhibitors, etc.: ≥ 3 months;

Exclusion Criteria:

1. Takayasu arteritis which only show lesions of vascular dilatation or aneurysm formation;
2. Takayasu arteritis patients who have received surgery related to revascularization for Takayasu arteritis (except percutaneoustransluminalangioplasty) within 3 months; or received percutaneoustransluminalangioplasty within 1 months;

3. Subjects with organ failure, meeting at least one of the following:

   3.1 Cardiac function: New York Heart Association grade 4;

   3.2 Glomerular filtration rate ≤ 60ml/min;

   3.3 Liver function： Child-pugh grade 2 and worse than grade 2;

   3.4 High frequency of amaurosis (flare on 3 consecutive days);

   3.5 Acute cerebral infarction or cerebral hemorrhage;

   3.6 Blood pressure> 160/100mmHg;

4. Suffer from other autoimmune diseases (eg, ANCA-associated vasculitis, systemic lupus erythematosus, Behcet's disease, etc.) besides Takayasu arteritis;
5. Serious or progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurological, or other coexisting medical conditions that are not associated with Takayasu's arteries but may result in unacceptable risks;
6. Co-morbidities as asthma that may require the use of medium to high doses of glucocorticoids (prednisone ≥ 10 mg/day or equivalent doses of prednisone equivalents) during the study period;
7. subjects with history of malignancy diseases;
8. Subjects with any serious acute or chronic infection;
9. Hepatitis B surface antigen positive or hepatitis B DNA positive;
10. Hepatitis C antibody positive;
11. Subjects with clinical or radiological or laboratory evidence of active tuberculosis;

12. Subjects with abnormal laboratory test results, meeting at least 1 of the following:

    12.1 Subjects with serum alanine aminotransferase (ALT) or glutamic-oxalacetic transaminase（AST）≥1.5 fold of the normal upper limit;

    12.2 Blood white blood cell count ≤4×10^9 / L;

    12.3 Platelet count ≤100 × 10^9 / L;

    12.4 Hemoglobin ≤85g / L;

    12.5 Other laboratory test abnormalities that may contribute to unacceptable risks for participants in this study;

13. Subjects who are allergic to any of the investigational drugs;
14. Use treatments and/or medication that are not allowed in this trial:

14.1 History of leflunomide treatment for at least 3 months but not effective;

14.2 Subjects who had undergone plasmapheresis or lymphocyte replacement or immunosorbent therapy in the last one year, or those who had planned to receive such treatments;

14.3 Patients who are willing to receive attenuated vaccine during the trial;

14.4 Subjects accepted or planned to have organ transplantation;