Tocilizumab and Tofacitinib in the Treatment of Vascular Behçet's Syndrome

NCT ID: NCT05845723

Last Updated: 2024-08-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2027-06-01

Brief Summary

This project aims to evaluate the efficacy and safety of the combination of glucocorticoids with tocilizumab or tofacitinib, compared to the traditional combination of glucocorticoids with cyclophosphamide in the treatment of vascular Behçet's syndrome.

Detailed Description

Behçet's Syndrome (BS) is a recurrent and systemic vasculitis, with an incidence rate of about 14/100,000 in China, higher than that in Europe and America. Vascular Behcet's Syndrome (VBS) is an important subtype of BS characterized by multiple venous and artery lesions. It affects 20-25% of BS patients, predominantly young adult males, and is the leading cause of mortality in BS patients (67%), especially in patients with aneurysms. Therefore, exploring the diagnosis and treatment strategies for VBS is key to improving the prognosis of BS.

This project aims to investigate the efficacy and safety of the combination of glucocorticoids (GCS) with the biologic agent tocilizumab or the targeted small molecule tofacitinib, compared to the combination of GCS with cyclophosphamide in the treatment of VBS aneurysms, as well as to screen for biomarkers related to the response of tocilizumab or tofacitinib, and to improve the assessment and treatment of VBS and establish a precision diagnosis and treatment strategy.

This is a Phase IIb, multi-center, randomized, open-label, GCS plus cyclophosphamide-controlled, parallel design, prospective clinical study. Patients will be randomly assigned to three groups in a 1:1:1 ratio (tocilizumab + GCS vs tofacitinib + GCS vs cyclophosphamide + GCS, 27:27:27) after screening and recruitment. Patients will be followed up every 4 weeks from weeks 0-12, and every 6 weeks from weeks 12-24. The primary endpoint is the complete remission (CR) rate at the 12th-week follow-up. All participants will undergo their final visit at 24 weeks.

Conditions

Aneurysm; Behcet Syndrome, Vascular Type

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab+GCS for VBS

Participants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks.

Group Type: EXPERIMENTAL

tocilizumab

Intervention Type: DRUG

Participants will receive intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks.

Tofacitinib+GCS for VBS

Participants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with oral tofacitinib 5mg twice a day for 24 weeks of treatment.

Group Type: EXPERIMENTAL

tofacitinib

Intervention Type: DRUG

Participants will receive tofacitinib 5mg twice a day for 24 weeks of treatment.

Cyclophosphamide+GCS for VBS

Participants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Participants will receive intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks.

Interventions

tocilizumab

Participants will receive intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks.

Intervention Type: DRUG

tofacitinib

Participants will receive tofacitinib 5mg twice a day for 24 weeks of treatment.

Intervention Type: DRUG

cyclophosphamide

Participants will receive intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks.

Intervention Type: DRUG

Other Intervention Names

ACTEMRA®; Xeljanz®; Endoxana

Eligibility Criteria

Inclusion Criteria

1． Understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.

2. Male and female subjects aged 18-65 years.

3． Fulfill the 2013 International Classification Criteria for Behcet's Disease (ICBD).

4． Patients with aneurysmal dilatation/aneurysm of the descending aorta and/or peripheral arteries confirmed by ultrasonography and/or computed tomography angiography (CTA).

5. Elevated acute phase reactants ESR and hs-CRP.

Exclusion Criteria

1. Cardiovascular manifestations that cannot be distinguished from giant cell arteritis, Burger's disease, or atherosclerotic aneurysm; infectious aneurysm;

2. Other active organ involvement related to BS that requires intensified immunosuppressive treatment, including gastrointestinal ulcers, uveitis, and parenchymal neurological involvement;

3. Patients with severe aneurysms requiring emergency intervention surgery; patients with elective surgery indications require the consensus between rheumatologists and vascular surgeons to determine inclusion or exclusion.

4. Severe organ dysfunction, including ALT, AST, and TBIL exceeding the upper limit of normal by more than 2 times, serum creatinine ≥ 133 mmol/L, white blood cell count < 3×10^9/L, ANC < 2×10^9/L, hemoglobin < 80g/L, platelet count < 100×10^9/L;

5. Active infection such as active tuberculosis, hepatitis B or C, syphilis, chronic EBV infection, persistent or severe bacterial or viral infection;

6. Primary or secondary immunodeficiency;

7. Malignant tumor;

8. Use of immunosuppressants such as Cyclosporin A (CsA), Azathioprine (AZA), Tacrolimus (TAC), Mycophenolate Mofetil (MMF), or Cyclophosphamide (CTX) within 1 month;

9. Use of biologics/small molecule drugs within 5 half-lives (baricitinib within 10 days; etanercept within 4 weeks; infliximab within 8 weeks; adalimumab, golimumab, ustekinumab, and abatacept within 10 weeks, secukinumab within 6 months, and previously use of tocilizumab and tofacitinib);

10. Pregnant, lactating, or planning a recent pregnancy;

11. Subjects who do not agree to or are unable to comply with regular visits.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jinjing Liu, M.D.

Role: CONTACT

wingsforjane@163.com

8613581605769

Wenjie Zheng, M.D.

Role: CONTACT

wenjzheng@gmail.com

8613661281939

Facility Contacts

Jinjing Liu

Role: primary

Other Identifiers

TCZ/TOF-VBS-PUMCH

Identifier Type: -

Identifier Source: org_study_id