NCT05199909

Safety and Efficacy of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia

Prospective, Single Arm and Open Clinical Observation of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To evaluate the safety and efficacy of zanubrutinib in the treatment of antiphospholipid syndrome with secondary thrombocytopenia in 10 patients.

Detailed description

Antiphospholipid syndrome (APS) is a disease spectrum characterized by thrombosis and/or pathological pregnancy, and characterized by persistent antiphospholipid antibodies (APL) positive in laboratory examination. The incidence of thrombocytopenia in APS patients is 29.6%. Thrombocytopenia is usually mild to moderate without clinical manifestations, and the risk of bleeding is low. The platelet count of most patients is \> 50 × 10\^9/L. If APS has severe thrombocytopenia and severe bleeding, it is very difficult to treat it. According to previous literature reports, Some patients were treated with hormones, rituximab and immunosuppressants. Platelets can be obviously increased, but they are easy to relapse and difficult to maintain. aPL is not obviously decreased and difficult to be completely eliminated. Thrombosis still occurs in some patients with obviously decreased platelets. Thrombopoietin receptor agonists increase the risk of thrombosis, which is a difficult point in hematology treatment at present. Bruton tyrosine kinase (BTK), a member of the Tec family of non-receptor tyrosine kinases, is expressed in all hematopoietic cells except T cells and terminal differentiated plasma cells. BTK is a key kinase in BCR signaling pathway, which regulates B cell proliferation, survival, differentiation and cytokine expression. BTK inhibitors can affect autoimmune diseases (AID) involving B cells and non-B cells through B cell receptor, Fc receptor and RANK receptor signals, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Besides its activity in B cells, BTK is also expressed in platelets and mediates the signal of cell surface receptor glycoprotein VI (GPVI). It is believed that BTK/Tec pathway may affect GP VI specific platelet signal deficiency and interfere with collagen adhesion and vWF-mediated platelet activation. BTK plays an important role in vWF-mediated signal transduction and GPIb-dependent thrombosis in vivo. Moreover, recent studies have found that BTK inhibitors can block the activation of platelets stimulated by FcγRIIA through antibody-mediated crosslinking (inducing platelet aggregation and secretion) or anti-CD9 antibody (only inducing platelet aggregation). Therefore, BTK inhibitors have certain antithrombotic effects at the same time. At present, there is no related report on BTK inhibitor in the treatment of APS abroad. BTK inhibitors can regulate B cell proliferation, survival, differentiation and cytokine expression, reduce antibody formation, and inhibit platelet adhesion and platelet activation, so they may have a good therapeutic effect on antiphospholipid syndrome. Therefore, the investigators designed this clinical trial to provide a new treatment option for the clinical treatment of antiphospholipid syndrome with secondary thrombocytopenia.

Conditions

• Antiphospholipid Syndrome
• Thrombocytopenia
• Treatment

Interventions

Type	Name	Description
DRUG	zanubrutinib	The initial dose is 80mg/day. If the treatment is ineffective after 4 weeks, and under the condition of good safety, the researcher will judge that the dosage should be added to 80mg twice/day，or a higher dose for oral maintenance. The maximum dose is 160mg twice a day. The duration of zanubrutinib is 24 weeks. In case of intolerable adverse reactions, such as severe infection, severe bleeding, hematopenia, arrhythmia, etc., investigator can reduce the dose of zanubrutinib, or withdraw from clinical trials as appropriate.

Timeline

• Start date: 2022-01-25
• Primary completion: 2023-12-31
• Completion: 2025-06-30
• First posted: 2022-01-20
• Last updated: 2025-02-24

Locations

2 sites across 1 country: China

Regulatory

• FDA-regulated drug study